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1、ReportOutlook 2024 Preview ReportSponsored by2December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)ForewordBiotech Innovation Drives Industry Changes In HealthcareForeword by Chris Smyth,President,ICON Biotech Numerous advancements have

2、impacted clinical development over the past year,including new modalities,breakthrough technologies,digital transformation,and novel clinical trial designs.We continue to see immense growth potential in the biotech industry with never-before-seen CRISPR technology and robust cell and gene therapies

3、progressing through late-stage clinical trials;however,we also see challenges with increased market competition and lack of funding for more complex treatments.In order to keep pace with innovation,it is becoming imperative for life sciences companies to make the necessary strategic pivots that will

4、 get products to the finish line more efficiently.As the worlds largest clinical research organization(CRO),ICON provides support and expertise to help companies mitigate the costs and risks associated with clinical development.We offer flexible partnership models that inform decision-making through

5、 extensive data resources and integrated clinical capabilities.From helping an emerging biotech meet its milestones,to assisting with the global launch of a first-in-class drug,our healthcare intelligence is what differentiates us from other CROs.Regulation,manufacturing,and other parts of clinical

6、development are growing more difficult to juggle as complexity rises,especially for smaller biotechs.With 8,000 experts working in our dedicated biotech division,ICON Biotech,we are dedicated to meeting the individualized needs of life sciences organizations.We are eager to explore the insights shar

7、ed at the upcoming 42nd Annual J.P.Morgan Healthcare Conference.In collaborating with subject matter experts,we see this as an opportunity to discuss challenges in this space and future strategies for improvement.We are particularly interested in understanding how the projected growth in R&D spendin

8、g among biotech companies will pan out in the coming years.There is nothing more important to ICON than facilitating the delivery of life-saving treatments to patients.Now that we are seeing more innovation in biotech than ever before,forming partnerships is the key to making scientific discoveries

9、a reality.By connecting with like-minded individuals,we can exchange knowledge and work together to form solutions that will improve healthcare and patient outcomes across the globe.We are pleased to partner with Citeline to deliver the following preview coverage of the J.P.Morgan Healthcare Confere

10、nce.To learn more about ICON Biotech,visit us at 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)ContentsBiopharma Embraces New Markets And New Tech 04The Biggest M&A Announcements Of 2023 Show Deals Are Getting Bigger 13Big Pharma Shouts,Ge

11、nerics And Biosimilars Whisper:M&A In 2023 17Medicare Price Setting And The Value Of Post-Approval R&D Spending 20The Future Of Obesity 264January 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)An unsteady geopolitical situation in eastern

12、Europe,worldwide inflation and the politicization of drug pricing in the US all made their mark on 2023.Making predictions about the biopharma world is always a tricky endeavor,but looking ahead into 2024 reveals an uptick in deal-making and perhaps the return of larger scale M&A,as big pharma feels

13、 the pressure to fill pipeline gaps at a faster rate.The unprecedented demand for new treatments in obesity has meant a couple of companies have fuller pockets and,in turn,more cash to put to work.The industry is moving closer to a large and extended patent cliff,a period of time from 2025 to the en

14、d of the decade when many of pharmas biggest revenue generating products are facing loss of exclusivity(see Exhibit 1).While the maturation of understanding around diseases such as obesity and long-awaited novel approvals in Alzheimers will start to fill the gap,there is not sufficient pipeline grow

15、th to make up the difference.According to Evaluate Pharma,there is$14.1bn in US sales at risk in 2024.As well as a look at dealmaking in the year ahead,In Vivo has highlighted a number of key development areas to watch in 2024 alongside anticipated clinical trial readouts.Deal-Making In 2024At Novem

16、bers BIO-Europe Fall conference,held in Munich,Ipsens EVP,chief business officer,Philippe Lopes Fernandes highlighted the challenging market in 2023.He told delegates during a panel discussion on Biopharma Embraces New Markets And New TechDecember 2023|In Vivo|5 OUTLOOK4|In Vivo|December 2023 OUTLOO

17、KAn unsteady geopolitical situation in eastern Europe,worldwide inflation and the politicization of drug pricing in the US all made their mark on 2023.Making predictions about the biopharma world is always a tricky endeavor,but looking ahead into 2024 reveals an uptick in deal-making and perhaps the

18、 return of larger scale M&A,as big pharma feels the pressure to fill pipeline gaps at a faster rate.The unprecedented demand for new treatments in obesity has meant a couple of companies have fuller pockets and,in turn,more cash to put to work.The industry is moving closer to a large and extended pa

19、tent cliff,a period of time from 2025 to the end of the decade when many of pharmas biggest revenue generating products are facing loss of exclusivity(see Exhibit 1).While the maturation of understanding around diseases such as obesity and long-awaited novel approvals in Alzheimers will start to fil

20、l the gap,there is not sufficient pipeline growth to make up the difference.According to Evaluate Pharma,there is$14.1bn in US sales at risk in 2024.As well as a look at dealmaking in the year ahead,In Vivo has highlighted a number of key development areas to watch in 2024 alongside anticipated clin

21、ical trial readouts.Deal-Making In 2024At Novembers BIO-Europe Fall conference,held in Munich,Ipsens EVP,chief business officer,Philippe Lopes Fernandes highlighted the challenging market in 2023.He told delegates during a panel discussion on navigating biopharma deal-making,“It has been a challengi

22、ng market,especially for public companies.Thank god for the biotech CEOs they are not all public,and right now it is much better to be a private biotech than a public one.The market is crazy,but the fundamentals are right.”Bradley Hardiman,senior director,Astellas Venture Management,described the si

23、tuation for companies looking for deals and raising funds as“tightly controlled at the moment.”“We hear about dry powder,venture capital funds,but there is still fear in the market and we need to flip that confidence level,”Hardiman said.“Dry powder on its own is pointless,but lets make some firewor

24、ks and do some deals.Pharma is very active but there is pressure on our share price:we are not immune to what is going on in the market.”SVP,head of global business development&alliance management at Merck KGaA,Matthias Mllenbeck,noted that M&A deals had focused on“post-proof of concept”assets in 20

25、23.But he expects more earlier stage deals in 2024.“The number of targets with totally de-risked assets is limited,”he said.“You will need to move into more earlier space,you will need to take more risk,despite having all of these uncertainties in the market.”Mllenbeck was cautious about the deal-ma

26、king environment in 2024.He predicts a slower rebound for the market.“It will be a tough time ahead of us.The financing environment will likely not change dramatically.We will not go back to a money-for-free set-up,which will also drive industry consolidation at all levels.If I talk with our friends

27、 at the law firms,they are pretty busy not with doing stuff for the buy side,but preparing for mergers and reverse mergers at the moment,to get the cash to the assets that people believe should be invested in.”New Growth Markets Obesity and CNS diseases are creating fresh growth areas for big pharma

28、(see Exhibit 2).In the first half of 2023,sales of Novo Nordisks Wegovy increased by 367%to DKK12.08bn($1.70bn)and analysts expect these figures to go through the roof in years to come,especially as Novo Nordisk expands its manufacturing capacity to address the current shortage of the drug.At a Q3 2

29、023 event in Copenhagen,Mads Krogsgaard Thomsen,CEO of the Novo Nordisk Foundation,said Novo Nordisk could be forgiven for not predicting such an impact as Wegovy was the first entrant into“a market that didnt exist,”given that previously the only clinical option for obese people was bariatric surge

30、ry.Other therapeutic options for treating obesity are emerging and the cardiovascular-metabolic(CVM)space has been reinvigorated in recent years.According to recent data presented at the Sachs Biotech in Europe Forum,clinical-stage cardiometabolic assets account for around 7%of the overall industry

31、R&D pipeline.The top five diseases by number of studies under the cardiometabolic R&D umbrella are diabetes,NASH,hypertension,obesity and heart failure,which collectively represent about 50%of the clinical-stage CVM pipeline.Biopharma Embraces New Markets And New Tech BY LUCIE ELLIS-TAITT,EXECUTIVE

32、EDITORNew markets,a patent cliff,an M&A rebound and clinical trial catalysts.How will it all play out for the biopharma sector in 2024?2023 Total Sales924,659-10,269-2,752-36,33610,7486,13593,557985,7422023 Patent Expiry Losses2024 Patent Expiry LossesOther LossesGrowth From 2023 LaunchesGrowth From

33、 2024 LaunchesOther Growth2024 Total SalesExhibit 1:2024 Drivers And BrakesExhibit 2:Therapy Area Growth 181614121086420-2-10-5052019-2023 CAGR2024-2028 CAGR10152025BloodRespiratoryEndocrineImmunomodulatorsGastro-IntestinalCardiovascularMusculoskeletal Genito-UrinaryOncologyCentral Nervous SystemDer

34、matologySystemic Anti-infectivesSensory OrgansSource:Evaluate Pharma Source:Evaluate Pharma By Lucie Ellis-Taitt,Executive EditorExecutive SummaryNew markets,a patent cliff,an M&A rebound and clinical trial catalysts.How will it all play out for the biopharma sector in 2024?5December 2023 Copyright

35、2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)Biopharma Embraces New Markets And New Technavigating biopharma deal-making,“It has been a challenging market,especially for public companies.Thank god for the biotech CEOs they are not all public,and right n

36、ow it is much better to be a private biotech than a public one.The market is crazy,but the fundamentals are right.”Bradley Hardiman,senior director,Astellas Venture Management,described the situation for companies looking for deals and raising funds as“tightly controlled at the moment.”“We hear abou

37、t dry powder,venture capital funds,but there is still fear in the market 18 and we need to flip that confidence level,”Hardiman said.“Dry powder on its own is 16 pointless,but lets make some fireworks and 14 do some deals.Pharma is very active but there is pressure on our share price:we are not 12 i

38、mmune to what is going on in the market.”SVP,head of global business development 10&alliance management at Merck KGaA,Matthias Mllenbeck,noted that M&A deals had focused on“post-proof of concept”assets in 2023.But he expects more earlier stage deals in 2024.“The number of targets with totally de-ris

39、ked assets is limited,”he said.“You will need to move into more earlier space,you will need to take more risk,despite having all of these uncertainties in the market.”Mllenbeck was cautious about the deal-making environment in 2024.He predicts a slower rebound for the market.“It will be a tough time

40、 ahead of us.The financing environment will likely not change dramatically.We will not go back to a money-for-free set-up,which will also drive industry consolidation at all levels.If I talk with our friends at the law firms,they are pretty busy not with doing stuff for the buy side,but preparing fo

41、r mergers and reverse mergers at the moment,to get the cash to the assets that people believe should be invested in.”Exhibit 1:2024 Drivers And BrakesDecember 2023|In Vivo|5 OUTLOOK4|In Vivo|December 2023 OUTLOOKAn unsteady geopolitical situation in eastern Europe,worldwide inflation and the politic

42、ization of drug pricing in the US all made their mark on 2023.Making predictions about the biopharma world is always a tricky endeavor,but looking ahead into 2024 reveals an uptick in deal-making and perhaps the return of larger scale M&A,as big pharma feels the pressure to fill pipeline gaps at a f

43、aster rate.The unprecedented demand for new treatments in obesity has meant a couple of companies have fuller pockets and,in turn,more cash to put to work.The industry is moving closer to a large and extended patent cliff,a period of time from 2025 to the end of the decade when many of pharmas bigge

44、st revenue generating products are facing loss of exclusivity(see Exhibit 1).While the maturation of understanding around diseases such as obesity and long-awaited novel approvals in Alzheimers will start to fill the gap,there is not sufficient pipeline growth to make up the difference.According to

45、Evaluate Pharma,there is$14.1bn in US sales at risk in 2024.As well as a look at dealmaking in the year ahead,In Vivo has highlighted a number of key development areas to watch in 2024 alongside anticipated clinical trial readouts.Deal-Making In 2024At Novembers BIO-Europe Fall conference,held in Mu

46、nich,Ipsens EVP,chief business officer,Philippe Lopes Fernandes highlighted the challenging market in 2023.He told delegates during a panel discussion on navigating biopharma deal-making,“It has been a challenging market,especially for public companies.Thank god for the biotech CEOs they are not all

47、 public,and right now it is much better to be a private biotech than a public one.The market is crazy,but the fundamentals are right.”Bradley Hardiman,senior director,Astellas Venture Management,described the situation for companies looking for deals and raising funds as“tightly controlled at the mo

48、ment.”“We hear about dry powder,venture capital funds,but there is still fear in the market and we need to flip that confidence level,”Hardiman said.“Dry powder on its own is pointless,but lets make some fireworks and do some deals.Pharma is very active but there is pressure on our share price:we ar

49、e not immune to what is going on in the market.”SVP,head of global business development&alliance management at Merck KGaA,Matthias Mllenbeck,noted that M&A deals had focused on“post-proof of concept”assets in 2023.But he expects more earlier stage deals in 2024.“The number of targets with totally de

50、-risked assets is limited,”he said.“You will need to move into more earlier space,you will need to take more risk,despite having all of these uncertainties in the market.”Mllenbeck was cautious about the deal-making environment in 2024.He predicts a slower rebound for the market.“It will be a tough

51、time ahead of us.The financing environment will likely not change dramatically.We will not go back to a money-for-free set-up,which will also drive industry consolidation at all levels.If I talk with our friends at the law firms,they are pretty busy not with doing stuff for the buy side,but preparin

52、g for mergers and reverse mergers at the moment,to get the cash to the assets that people believe should be invested in.”New Growth Markets Obesity and CNS diseases are creating fresh growth areas for big pharma(see Exhibit 2).In the first half of 2023,sales of Novo Nordisks Wegovy increased by 367%

53、to DKK12.08bn($1.70bn)and analysts expect these figures to go through the roof in years to come,especially as Novo Nordisk expands its manufacturing capacity to address the current shortage of the drug.At a Q3 2023 event in Copenhagen,Mads Krogsgaard Thomsen,CEO of the Novo Nordisk Foundation,said N

54、ovo Nordisk could be forgiven for not predicting such an impact as Wegovy was the first entrant into“a market that didnt exist,”given that previously the only clinical option for obese people was bariatric surgery.Other therapeutic options for treating obesity are emerging and the cardiovascular-met

55、abolic(CVM)space has been reinvigorated in recent years.According to recent data presented at the Sachs Biotech in Europe Forum,clinical-stage cardiometabolic assets account for around 7%of the overall industry R&D pipeline.The top five diseases by number of studies under the cardiometabolic R&D umb

56、rella are diabetes,NASH,hypertension,obesity and heart failure,which collectively represent about 50%of the clinical-stage CVM pipeline.Biopharma Embraces New Markets And New Tech BY LUCIE ELLIS-TAITT,EXECUTIVE EDITORNew markets,a patent cliff,an M&A rebound and clinical trial catalysts.How will it

57、all play out for the biopharma sector in 2024?2023 Total Sales924,659-10,269-2,752-36,33610,7486,13593,557985,7422023 Patent Expiry Losses2024 Patent Expiry LossesOther LossesGrowth From 2023 LaunchesGrowth From 2024 LaunchesOther Growth2024 Total SalesExhibit 1:2024 Drivers And BrakesExhibit 2:Ther

58、apy Area Growth 181614121086420-2-10-5052019-2023 CAGR2024-2028 CAGR10152025BloodRespiratoryEndocrineImmunomodulatorsGastro-IntestinalCardiovascularMusculoskeletal Genito-UrinaryOncologyCentral Nervous SystemDermatologySystemic Anti-infectivesSensory OrgansSource:Evaluate Pharma Source:Evaluate Phar

59、ma 6December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)New Growth Markets Obesity and CNS diseases are creating fresh growth areas for big pharma(see Exhibit 2).In the first half of 2023,sales of Novo Nordisks Wegovy increased by 367%t

60、o DKK12.08bn($1.70bn)and analysts expect these figures to go through the roof in years to come,especially as Novo Nordisk expands its manufacturing capacity to address the current shortage of the drug.At a Q3 2023 event in Copenhagen,Mads Krogsgaard Thomsen,CEO of the Novo Nordisk Foundation,said No

61、vo Nordisk could be forgiven for not predicting such an impact as Wegovy was the first entrant into“a market that didnt exist,”given that previously the only clinical option for obese people was bariatric surgery.Other therapeutic options for treating obesity are emerging and the cardiovascular-meta

62、bolic(CVM)space has been reinvigorated in recent years.According to recent data presented at the Sachs Biotech in Europe Forum,clinical-stage cardiometabolic assets account for around 7%of the overall industry R&D pipeline.The top five diseases by number of studies under the cardiometabolic R&D umbr

63、ella are diabetes,NASH,hypertension,obesity and heart failure,which collectively represent about 50%of the clinical-stage CVM pipeline.Novo Nordisk is also expanding its CVM pipeline.In October 2023,the company announced it was acquiring ocedurenone for uncontrolled hypertension,with potential appli

64、cation in cardiovascular and kidney disease,from KBP Biosciences for up to$1.3bn.Ocedurenone is an orally administered,small molecule,non-steroidal mineralocorticoid receptor antagonist that is being tested in the Phase III CLARION-CKD trial in patients with uncontrolled hypertension and advanced ch

65、ronic kidney disease.Novo Nordisk expects to initiate Phase III trials for ocedurenone in additional cardiovascular and kidney disease indications in the coming years.Biopharma Embraces New Markets And New TechExhibit 2:Therapy Area GrowthDecember 2023|In Vivo|5 OUTLOOK4|In Vivo|December 2023 OUTLOO

66、KAn unsteady geopolitical situation in eastern Europe,worldwide inflation and the politicization of drug pricing in the US all made their mark on 2023.Making predictions about the biopharma world is always a tricky endeavor,but looking ahead into 2024 reveals an uptick in deal-making and perhaps the

67、 return of larger scale M&A,as big pharma feels the pressure to fill pipeline gaps at a faster rate.The unprecedented demand for new treatments in obesity has meant a couple of companies have fuller pockets and,in turn,more cash to put to work.The industry is moving closer to a large and extended pa

68、tent cliff,a period of time from 2025 to the end of the decade when many of pharmas biggest revenue generating products are facing loss of exclusivity(see Exhibit 1).While the maturation of understanding around diseases such as obesity and long-awaited novel approvals in Alzheimers will start to fil

69、l the gap,there is not sufficient pipeline growth to make up the difference.According to Evaluate Pharma,there is$14.1bn in US sales at risk in 2024.As well as a look at dealmaking in the year ahead,In Vivo has highlighted a number of key development areas to watch in 2024 alongside anticipated clin

70、ical trial readouts.Deal-Making In 2024At Novembers BIO-Europe Fall conference,held in Munich,Ipsens EVP,chief business officer,Philippe Lopes Fernandes highlighted the challenging market in 2023.He told delegates during a panel discussion on navigating biopharma deal-making,“It has been a challengi

71、ng market,especially for public companies.Thank god for the biotech CEOs they are not all public,and right now it is much better to be a private biotech than a public one.The market is crazy,but the fundamentals are right.”Bradley Hardiman,senior director,Astellas Venture Management,described the si

72、tuation for companies looking for deals and raising funds as“tightly controlled at the moment.”“We hear about dry powder,venture capital funds,but there is still fear in the market and we need to flip that confidence level,”Hardiman said.“Dry powder on its own is pointless,but lets make some firewor

73、ks and do some deals.Pharma is very active but there is pressure on our share price:we are not immune to what is going on in the market.”SVP,head of global business development&alliance management at Merck KGaA,Matthias Mllenbeck,noted that M&A deals had focused on“post-proof of concept”assets in 20

74、23.But he expects more earlier stage deals in 2024.“The number of targets with totally de-risked assets is limited,”he said.“You will need to move into more earlier space,you will need to take more risk,despite having all of these uncertainties in the market.”Mllenbeck was cautious about the deal-ma

75、king environment in 2024.He predicts a slower rebound for the market.“It will be a tough time ahead of us.The financing environment will likely not change dramatically.We will not go back to a money-for-free set-up,which will also drive industry consolidation at all levels.If I talk with our friends

76、 at the law firms,they are pretty busy not with doing stuff for the buy side,but preparing for mergers and reverse mergers at the moment,to get the cash to the assets that people believe should be invested in.”New Growth Markets Obesity and CNS diseases are creating fresh growth areas for big pharma

77、(see Exhibit 2).In the first half of 2023,sales of Novo Nordisks Wegovy increased by 367%to DKK12.08bn($1.70bn)and analysts expect these figures to go through the roof in years to come,especially as Novo Nordisk expands its manufacturing capacity to address the current shortage of the drug.At a Q3 2

78、023 event in Copenhagen,Mads Krogsgaard Thomsen,CEO of the Novo Nordisk Foundation,said Novo Nordisk could be forgiven for not predicting such an impact as Wegovy was the first entrant into“a market that didnt exist,”given that previously the only clinical option for obese people was bariatric surge

79、ry.Other therapeutic options for treating obesity are emerging and the cardiovascular-metabolic(CVM)space has been reinvigorated in recent years.According to recent data presented at the Sachs Biotech in Europe Forum,clinical-stage cardiometabolic assets account for around 7%of the overall industry

80、R&D pipeline.The top five diseases by number of studies under the cardiometabolic R&D umbrella are diabetes,NASH,hypertension,obesity and heart failure,which collectively represent about 50%of the clinical-stage CVM pipeline.Biopharma Embraces New Markets And New Tech BY LUCIE ELLIS-TAITT,EXECUTIVE

81、EDITORNew markets,a patent cliff,an M&A rebound and clinical trial catalysts.How will it all play out for the biopharma sector in 2024?2023 Total Sales924,659-10,269-2,752-36,33610,7486,13593,557985,7422023 Patent Expiry Losses2024 Patent Expiry LossesOther LossesGrowth From 2023 LaunchesGrowth From

82、 2024 LaunchesOther Growth2024 Total SalesExhibit 1:2024 Drivers And BrakesExhibit 2:Therapy Area Growth 181614121086420-2-10-5052019-2023 CAGR2024-2028 CAGR10152025BloodRespiratoryEndocrineImmunomodulatorsGastro-IntestinalCardiovascularMusculoskeletal Genito-UrinaryOncologyCentral Nervous SystemDer

83、matologySystemic Anti-infectivesSensory OrgansSource:Evaluate Pharma 7December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)In the year ahead,a number of clinical trial readouts are expected for drugs targeting Alzheimers disease(AD).CNS

84、diseases have seen renewed interest following the approval of new treatments for Parkinsons and Alzheimers disease.The unmet need in is huge,as is the market potential for drugs able to demonstrate a slowing of progression in symptoms or those able to tackle underlying causes of CNS conditions.“Dry

85、powder on its own is pointless,lets make some fireworks.”Bradley HardimanThe landmark,yet controversial,US approval of Biogen and Eisais anti-amyloid antibody Aduhelm came despite Phase III clinical trial data resulting in one positive and one negative study.In its announcement of this groundbreakin

86、g approval,the US Food and Drug Administration(FDA)acknowledged there was some uncertainty around the data,but reiterated that the treatment was the first to show a benefit in amyloid plaque reduction,thus targeting the underlying disease pathology rather than masking symptoms.The FDAs accelerated a

87、pproval of Aduhelm based on amyloid reduction rather than cognitive improvement lowered the bar for approval,though market access barriers remain.In July 2023,Eisais Leqembi(lecanemab)became the first anti-amyloid antibody to gain full approval from the FDA,after receiving accelerated approval from

88、the agency in January the same year.Though competitor Eli Lillys donanemab may have a slight efficacy advantage,physicians may favor Leqembis better safety profile.A traditional approval decision for donanemab is expected by the end of 2023.Despite uncertainties around efficacy and barriers to acces

89、s,the high unmet need may ultimately create a lucrative market for anti-amyloid antibodies.If positive,data from subcutaneous formulations of anti-amyloid antibodies may generate excitement about a more desirable formulation coming down the pipeline.Datamonitor Healthcare analyst Pamela Spicer told

90、In Vivo,“Eli Lillys next-generation plaque-removing antibody remternetug targets the same pyroglutamate residue as donanemab but is designed to avoid the level of anti-drug antibodies.”Lilly has initiated the Phase III TRAILRUNNER-ALZ 1 study evaluating a subcutaneous injection and an intravenous in

91、fusion of remternetug.A subcutaneous formulation of Leqembi is also being developed.Spicer highlighted biomarker results presented from a Phase I/IIa study of Biogens BIIB080 in patients with mild AD as“the most exciting data to emerge from 2023.”BIIB080 is an antisense oligonucleotide designed to r

92、educe concentrations of MAPT messenger RNA and thus reduce the production of all tau species within the CNS.During the study,patients on placebo maintained relatively stable levels of CSF tau,whereas patients on BIIB080 demonstrated a dose-dependent reduction in CSF tau over the three-month treatmen

93、t period.In the two highest dose cohorts,CSF tau continued to decrease after treatment was discontinued,though patients on the lower doses saw a rebound in their CSF tau levels once treatment stopped.With regard to the tau PET imaging results,which reflect aggregated forms of tau in the brain,patien

94、ts that received placebo demonstrated a slight increase from baseline in tau across the majority of brain regions assessed.This is consistent with natural disease progression.For treated patients,those on the highest dose showed a slight reduction in tau burden across all brain regions.Although tau

95、tangles,along with beta-amyloid plaques,are considered hallmark pathological features of Alzheimers disease,tau-based strategies remain underrepresented in the late-phase clinical pipeline.Biopharma Embraces New Markets And New Tech8December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citel

96、ine company(Unauthorized photocopying prohibited)Cancer Retakes Top SpotEach year in its Clinical Trials Roundup,Citelines Trialtrove team analyzes the top 10 diseases for clinical trial activity to get a view of where research efforts are taking place.The most recent dataset looks at all trials in

97、the full year of 2022.After a two-year reign,COVID-19 finally gave up its number one spot back to an oncology disease(unspecified solid tumor,566 trials),though it continues to exert its presence in a close second place(563 trials).Looking more broadly at therapeutic areas,oncology continued to be t

98、he top-ranking development area with a clear lead,even though its trial initiations were down by 10%.Within oncology,bladder,prostate and ovarian cancers will potentially gain more attention in 2024.Datamonitor Healthcare analyst Millie Gray told In Vivo that although bladder cancer is a very diffic

99、ult disease to treat,“there has been a hub of research around this indication and the work is finally coming to fruition.”She noted that in 2023,Merck&Co.s Keytruda(pembrolizumab)plus Seagens Padcev(enfortumab)met its primary endpoint in the Phase III EV-302 trial,becoming the first targeted combina

100、tion therapy to show an overall survival benefit over the current first-line standard of care,carboplatin or cisplatin in combination with gemcitabine.“This will become the new standard of care and will change the treatment paradigm,”Gray said.In prostate cancer,there is excitement around Novartis A

101、Gs radioligand therapy Pluvicto(lutetium vipivotide tetraxetan)and its use in wider prostate cancer indications.The product won its first US approval in March 2022 for the treatment of PSMA-positive metastatic castration-resistant prostate cancer(mCRPC)patients who had previously been treated with b

102、oth androgen-receptor pathway inhibitor(ARPI)therapy and taxane-based chemotherapy,based on the VISION study.Data are expected in the first half of 2024 from the Phase III PSMAddition trial,which is looking at Pluvicto in the metastatic hormone-sensitive prostate cancer indication(mHSPC).This lucrat

103、ive setting is mainly comprised of de novo metastatic prostate cancer patients,and is heavily dominated by hormonal therapies such as Xtandi and abiraterone.“Competition here will be fierce but an approval will widen Pluvictos reach in prostate cancer,bringing it a step closer to being ubiquitous ac

104、ross prostate cancer settings,”Gray said.Another key readout from the PSMAfore trial,looking at patients in the pre-chemo setting,will likely lead to a pre-chemo(but post next-gen hormonal therapy)approval sometime in 2024,further expanding Pluvictos reach.Also,a well-established standard of care,Xt

105、andi,is expected to gain approvals in the high-risk biochemically recurrent setting based on data from the Phase III EMBARK trial.Gray noted that a regulatory nod for Xtandi in this setting“could change how a large proportion of prostate cancer patients are treated.”Datamonitor analyst Ellie Davenpo

106、rt also spotlighted the first-line advanced ovarian cancer setting as an area likely to gain prominence in 2024.This indication is expected to see PD-1 and PARP inhibitor combinations gain approvals from 2024.The Phase III DUO-O trial investigating Imfinzi plus Lynparza is the only trial to read out

107、 so far,but more are expected in 2024.Currently,only PARP inhibitors,bevacizumab and chemotherapies are treatment options for untreated advanced ovarian cancer.“The launches of PD-1/PD-L1 inhibitor combinations have the potential to shift the first-line treatment paradigm through the introduction of

108、 new options for patients without a BRCA1/2 mutation or HRD deficiency,”Davenport told In Vivo.(See Table 1 for late-stage cancer trial data expected in 2024.)Biopharma Embraces New Markets And New Tech9December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photo

109、copying prohibited)Biopharma Embraces New Markets And New TechTable 1:Select Oncology Trial Readouts To Watch For6|In Vivo|December 2023December 2023|In Vivo|7 OUTLOOK OUTLOOKNovo Nordisk is also expanding its CVM pipeline.In October 2023,the company announced it was acquiring ocedurenone for uncont

110、rolled hypertension,with potential application in cardiovascular and kidney disease,from KBP Biosciences for up to$1.3bn.Ocedurenone is an orally administered,small molecule,non-steroidal mineralocorticoid receptor antagonist that is being tested in the Phase III CLARION-CKD trial in patients with u

111、ncontrolled hypertension and advanced chronic kidney disease.Novo Nordisk expects to initiate Phase III trials for ocedurenone in additional cardiovascular and kidney disease indications in the coming years.In the year ahead,a number of clinical trial readouts are expected for drugs targeting Alzhei

112、mers disease(AD).CNS diseases have seen renewed interest following the approval of new treatments for Parkinsons and Alzheimers disease.The unmet need in is huge,as is the market potential for drugs able to demonstrate a slowing of progression in symptoms or those able to tackle underlying causes of

113、 CNS conditions.The landmark,yet controversial,US approval of Biogen and Eisais anti-amyloid antibody Aduhelm came despite Phase III clinical trial data resulting in one positive and one negative study.In its announcement of this groundbreaking approval,the US Food and Drug Administration(FDA)acknow

114、ledged there was some uncertainty around the data,but reiterated that the treatment was the first to show a benefit in amyloid plaque reduction,thus targeting the underlying disease pathology rather than masking symptoms.The FDAs accelerated approval of Aduhelm based on amyloid reduction rather than

115、 cognitive improvement lowered the bar for approval,though market access barriers remain.In July 2023,Eisais Leqembi(lecanemab)became the first anti-amyloid antibody to gain full approval from the FDA,after receiving accelerated approval from the agency in January the same year.Though competitor Eli

116、 Lillys donanemab may have a slight efficacy advantage,physicians may favor Leqembis better safety profile.A traditional approval decision for donanemab is expected by the end of 2023.Despite uncertainties around efficacy and barriers to access,the high unmet need may ultimately create a lucrative m

117、arket for anti-amyloid antibodies.If positive,data from subcutaneous formulations of anti-amyloid antibodies may generate excitement about a more desirable formulation coming down the pipeline.Datamonitor Healthcare analyst Pamela Spicer told In Vivo,“Eli Lillys next-generation plaque-removing antib

118、ody remternetug targets the same pyroglutamate residue as donanemab but is designed to avoid the level of anti-drug antibodies.”Lilly has initiated the Phase III TRAILRUNNER-ALZ 1 study evaluating a subcutaneous injection and an intravenous infusion of remternetug.A subcutaneous formulation of Leqem

119、bi is also being developed.Spicer highlighted biomarker results presented from a Phase I/IIa study of Biogens BIIB080 in patients with mild AD as“the most exciting data to emerge from 2023.”BIIB080 is an antisense oligonucleotide designed to reduce concentrations of MAPT messenger RNA and thus reduc

120、e the production of all tau species within the CNS.During the study,patients on placebo maintained relatively stable levels of CSF tau,whereas patients on BIIB080 demonstrated a dose-dependent reduction in CSF tau over the three-month treatment period.In the two highest dose cohorts,CSF tau continue

121、d to decrease after treatment was discontinued,though patients on the lower doses saw a rebound in their CSF tau levels once treatment stopped.With regard to the tau PET imaging results,which reflect aggregated forms of tau in the brain,patients that received placebo demonstrated a slight increase f

122、rom baseline in tau across the majority of brain regions assessed.This is consistent with natural disease progression.For treated patients,those on the highest dose showed a slight reduction in tau burden across all brain regions.Although tau tangles,along with beta-amyloid plaques,are considered ha

123、llmark pathological features of Alzheimers disease,tau-based strategies remain underrepresented in the late-phase clinical pipeline.Cancer Retakes Top SpotEach year in its Clinical Trials Roundup,Citelines Trialtrove team analyzes the top 10 diseases for clinical trial activity to get a view of wher

124、e research efforts are taking place.The most recent dataset looks at all trials in the full year of 2022.After a two-year reign,COVID-19 finally gave up its number one spot back to an oncology disease(unspecified solid tumor,566 trials),though it continues to exert its presence in a close second pla

125、ce(563 trials).Looking more broadly at therapeutic areas,oncology continued to be the top-ranking development area with a clear lead,even though its trial initiations were down by 10%.Within oncology,bladder,prostate and ovarian cancers will potentially gain more attention in 2024.Datamonitor Health

126、care analyst Millie Gray told In Vivo that although bladder cancer is a very difficult disease to treat,“there has been a hub of research around this indication and the work is finally coming to fruition.”She noted that in 2023,Merck&Co.s Keytruda(pembrolizumab)plus Seagens Padcev(enfortumab)met its

127、 primary endpoint in the Phase III EV-302 trial,becoming the first targeted combination therapy to show an overall survival benefit over the current first-line standard of care,carboplatin or cisplatin in combination with gemcitabine.“This will become the new standard of care and will change the tre

128、atment paradigm,”Gray said.In prostate cancer,there is excitement around Novartis AGs radioligand therapy Pluvicto(lutetium vipivotide tetraxetan)and its use in wider prostate cancer indications.The product won its first US approval in March 2022 for the treatment of PSMA-positive metastatic castrat

129、ion-resistant prostate cancer(mCRPC)patients who had previously been treated with both androgen-receptor pathway inhibitor(ARPI)therapy and taxane-based chemotherapy,based on the VISION study.Data are expected in the first half of 2024 from the Phase III PSMAddition trial,which is looking at Pluvict

130、o in the metastatic hormone-sensitive prostate cancer indication(mHSPC).This lucrative setting is mainly comprised of de novo metastatic prostate cancer patients,and is heavily dominated by hormonal therapies such as Xtandi and abiraterone.“Competition here will be fierce but an approval will widen

131、Pluvictos reach in prostate cancer,bringing it a step closer to being ubiquitous across prostate cancer settings,”Gray said.Another key readout from the PSMAfore trial,looking at patients in the pre-chemo setting,will likely lead to a pre-chemo(but post next-gen hormonal therapy)approval sometime in

132、 2024,further expanding Pluvictos reach.Also,a well-established standard of care,Xtandi,is expected to gain approvals in the high-risk biochemically recurrent setting based on data from the Phase III EMBARK trial.Gray noted that a regulatory nod for Xtandi in this setting“could change how a large pr

133、oportion of prostate cancer patients are treated.”Datamonitor analyst Ellie Davenport also spotlighted the first-line advanced ovarian cancer setting as an area likely to gain prominence in 2024.This indication is expected to see PD-1 and PARP inhibitor combinations gain approvals from 2024.The Phas

134、e III DUO-O trial investigating Imfinzi plus Lynparza is the only trial to read out so far,but more are expected in 2024.Currently,only PARP inhibitors,bevacizumab and chemotherapies are treatment options for untreated advanced ovarian cancer.“The launches of PD-1/PD-L1 inhibitor combinations have t

135、he potential to shift the first-line treatment paradigm through the introduction of new options for patients without a BRCA1/2 mutation or HRD deficiency,”Davenport told In Vivo.(See Table 1 for late-stage cancer trial data expected in 2024.)Drug/DeveloperClinical Trial Analysts Comments Enhertu/Dai

136、ichi SankyoPhase III DESTINY-Breast06HR+/HER2-low breast cancer patients who have progressed on endocrine therapy in the metastatic setting.Positive data will cement its use as the leading ADC for HR+/HER2-low breast cancer,where it already has an approval based on the Phase III DESTINY-Breast04 tri

137、al.Crohns disease$6.2bnImfinzi/AstraZenecaPhase III NILEImfinzi in combination with standard of care chemotherapy and Imfinzi in combination with tremelimumab and standard of care chemotherapy versus standard of care chemotherapy alone in patients with unresectable locally advanced or metastatic bla

138、dder cancer.Keytruda is currently leading ICI in this setting.Psoriasis$3.9bnKrazati/Mirati Phase III KRYSTAL-12Krazati and JDQ443 are being tested in patients with previously treated KRASp.G12C-mutated NSCLC.Patients with KRAS-positive NSCLC were previously deemed undruggable and responded poorly t

139、o immunotherapy treatments.If either Krazati or JDQ443 can demonstrate a survival benefit in a Phase III trial,they will likely become the treatment of choice.Ulcerative colitis$1.2bnJDQ443/NovartisPhase III KontRASt-02See aboveJemperli combinations/GSKPhase II/III COSTARGSK is testing a triplet of

140、cobolimab in combination with Jemperli and docetaxel,as well as a doublet of Jemperli plus docetaxel,against docetaxel alone in the Phase III COSTAR Lung trial in patients with advanced NSCLC whose disease has progressed on previous PD-1/PD-L1 inhibitor treatment.The post-immunotherapy setting is a

141、setting of high unmet need and represents a large commercial opportunity as there is currently no standard of care,and often patients are treated with chemotherapy.“Dry powder on its own is pointless,lets make some fireworks.”Bradley Hardiman Table 1:Select Oncology Trial Readouts To Watch For 8|In

142、Vivo|December 2023December 2023|In Vivo|9 OUTLOOK OUTLOOKDrug/DeveloperClinical Trial Analysts Comments patritumab deruxtecan/Daiichi SankyoPhase III HERTHENA-Lung02The HER3-directed ADC patritumab deruxtecan is the first anti-HER3 monoclonal antibody in development for the treatment of NSCLC.Daiich

143、i Sankyo is investigating patritumab deruxtecan in the Phase III HERTHENA-Lung02 trial in patients with EGFR-mutated advanced or metastatic NSCLC whose disease has progressed following treatment with a third-generation EGFR inhibitor.Tagrisso,a third-generation EGFR inhibitor,is estimated to capture

144、 6070%of the first-line advanced or metastatic EGFR-positive NSCLC market,and a standard of care treatment following disease progression is yet to be determined.Typically,patients are not retreated with EGFR inhibitor monotherapy,meaning chemotherapy is often the choice of treatment and these patien

145、ts are lacking an active and tolerable targeted treatment.Opdivo/BMSPhase III CheckMate 9DXTesting Opdivo in the adjuvant setting for the treatment of early-stage HCC.Currently,early-stage HCC patients are primarily treated with liver transplants or surgical resection,or with locoregional therapies

146、if they are not candidates for surgery.Imfinzi/AstraZenecaPhase III EMERALD-2Testing Imfinzi with or without bevacizumab as an adjuvant therapy in patients with HCC who are at high risk of recurrence after curative hepatic resection or ablation.As with Opdivo,there is an unmet need for an efficaciou

147、s but tolerable therapy for these early-stage HCC patients.Closing The Door On COVID?For many people,the pandemic is being placed firmly in the past as new worries take precedent the challenging economic climate,upcoming election years and tougher regulation,as a few examples.However,winter of 2023

148、will be a key test for countries that have seen declining levels of COVID-19 following successful vaccine programs.The biopharma sector is demonstrating a mixed response,with some companies investing in advanced vaccine options while others step away from COVID R&D.With the Omicron variant now the d

149、ominant strain globally,accounting for 99%of new cases in the US and Europe,efficacy against this strain is paramount to long-term commercial potential.So far,Pfizer/BioNTechs Comirnaty and Modernas Spikevax have shown the most robust efficacy data against the Omicron variant,with vaccine efficacy o

150、f 90%against hospitalization and death after a third booster dose,though protection wanes considerably after four months.Inactivated vaccines have played a crucial role in primary vaccination series in China,India,Russia,and other emerging markets.However,as domestically produced vectored,protein su

151、bunit and recently mRNA vaccines reach emerging markets,inactivated vaccines are expected to progressively lose market share.Many pharma companies appear to be moving away from COVID R&D.Assessing the clinical trial landscape for industry-sponsored trials shows that in 2022 the number of trial initi

152、ations decreased by 7%overall.However,when excluding COVID-19 trials from this analysis,this reduces to a 4%decline,reflecting the industrys survival mode since 2021.“We have been seeing significant pipeline attrition as minor players have reallocated resources to other,more profitable indications f

153、rom approximately 2021 onwards,”noted Datamonitor Healthcare analysts Natasha Boliter and Charlotte Holmes.“This phenomenon is particularly encouraged by the speed of COVID-19 mutation,demanding annual,variant-specific vaccines,and the excellent efficacy results(exceeding 90%)of currently marketed a

154、ssets.However,we are also seeing pipeline discontinuations from larger vaccine manufacturers.This was heralded by Sanofi in 2021,which suspended development of its own mRNA vaccine,despite reporting positive Phase I/II results,stating that the program was no longer commercially viable given the domi

155、nance of the other mRNA vaccines.”(see Exhibit 3).There is uncertainty even for giants in the COVID-19 vaccine industry.Pfizer,for example,is encountering constraints in the COVID-19 market,with predicted revenues for 2023 less than 60%of the preceding year.“In light of this,Pfizer has announced an

156、enterprise-wide cost realignment program in response to the unpredictable demand caused by the transition from the government-sponsored pandemic phase to the privately or individually funded endemic phase,”Boliter and Holmes highlighted.“Currently,it is uncertain what this will mean for its pan-resp

157、iratory programs or its future seasonal,variant-specific vaccines.”There is still R&D interest in COVID,but the pipeline today consists of mainly next-generation mAbs,variant-specific adaptations of currently marketed vaccines and the pan-respiratory combination vaccines.Looking ahead into the first

158、 half of 2024,AstraZeneca is expected to announce efficacy data from the Phase I/III SUPERNOVA study for its next-generation mAb AZD3152.Similarly,Invivyd is expecting primary endpoint data from the Phase III CANOPY trial of its next-generation mAb VYD222 by early 2024.Generative AIArtificial intell

159、igence was a buzzword in almost all panel discussions at the November 2023 BIO-Europe conference.There is a lot of promise,but also a lot of confusion about best uses.The speed of technology development in AI is outpacing biopharma.Generative AI,building upon advances in deep learning,is both a prom

160、ising and a concerning technology.“If harnessed securely and ethically,leveraging multi-modal data,such as text,images,and videos,generative AI can help pharmaceutical companies identify unmet clinical needs and expedite clinical planning and execution strategies,”said Luca Parisi,Citelines director

161、 of clinical analytics and data science.In both drug discovery and repurposing,generative AI can play a role in respectively devising novel molecules and elucidating relationships that may inform drug repositioning.“Generative AI-powered drug repurposing efforts may include both approved drugs in ce

162、rtain indications and help in capitalizing on those drugs that did not make it through Phase II studies in some indications but could be better suited for treating other indications,”Parisi said.He also highlighted the potential of leveraging real-world data,especially electronic health records and

163、medical images.Here,generative AI“can help to titrate treatments on a subject-specific basis,accelerating the transformational paradigm of personalized medicine and the impact it can bring to providing subject-specific,lifesaving or life-enhancing treatments faster.”Despite the potential uses and cl

164、ear excitement around generative AI tools,there are challenges for using the technology in a health care setting.“It is crucial to ensure HIPAA,GDPR(where applicable),and GxP compliance by design,thus leveraging appropriate infrastructure and technologies to guarantee that data security and confiden

165、tiality,and patient privacy are adhered to,”Parisi warned.“Furthermore,considering the scale of the data required to train such large generative AI models,appropriate analyses to detect and minimize biases and ensure representativeness in the underlying data are of paramount importance to provide cl

166、inically relevant,accurate and reliable recommendations to design more recruitable,diverse,inclusive clinical trials,and inform operational workflows throughout the clinical trial lifecycle objectively.”The key challenges ahead towards a fruitful,sustainable adoption of generative AI tools are:1.dat

167、a quality,given the scale of the data required;2.achieving a seamless integration of such advanced technologies in clinical workflows;3.tackling ethical considerations by design;4.ensuring replicability and reproducibility at all stages;5.clinical validation of the outputs derived from these technol

168、ogies.The main expectation for the biopharma sector is to accelerate the continuum of the drug development pipeline and clinical trial lifecycle,increasing both time and cost savings.A Health Care Metamorphosis Biopharma is on the edge of a new era driven by the need to replenish pipelines and the e

169、volution of technology.In 2024,the sector will see 70 key launches from around 65 drug brands.A notable proportion of these launches have the potential to shift treatment practices.AstraZenecas Imfinzi is just one example,with five label expansions expected in the coming year.After a period of easy

170、fund raising and busy deal-making in 2020-2021,tough times have hit the sector.But there is positivity for the volume of M&A deals to rise again,even if the financial markets do not bounce back as quickly as some might hope in the coming 12 months.Regulatory changes will have an impact from 2024 int

171、o the coming few years,in the form of both intentional and unintended consequences.Astellass Hardiman summarized the state of the sector:“We have seen a myriad of challenges over the course of time.As a testament to our industry,we always overcome these I am confident and optimistic that we can agai

172、n.”20204.46396.38105.24239.25530.43226.76324.06722.71722.02720212022202320242025202620272028Exhibit 3:Worldwide Sales For COVID-19 Treatments And ProphylaxisSource:Evaluate Pharma 10December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)Cl

173、osing The Door On COVID?For many people,the pandemic is being placed firmly in the past as new worries take precedent the challenging economic climate,upcoming election years and tougher regulation,as a few examples.However,winter of 2023 will be a key test for countries that have seen declining lev

174、els of COVID-19 following successful vaccine programs.The biopharma sector is demonstrating a mixed response,with some companies investing in advanced vaccine options while others step away from COVID R&D.With the Omicron variant now the dominant strain globally,accounting for 99%of new cases in the

175、 US and Europe,efficacy against this strain is paramount to long-term commercial potential.So far,Pfizer/BioNTechs Comirnaty and Modernas Spikevax have shown the most robust efficacy data against the Omicron variant,with vaccine efficacy of 90%against hospitalization and death after a third booster

176、dose,though protection wanes considerably after four months.Inactivated vaccines have played a crucial role in primary vaccination series in China,India,Russia,and other emerging markets.However,as domestically produced vectored,protein subunit and recently mRNA vaccines reach emerging markets,inact

177、ivated vaccines are expected to progressively lose market share.Many pharma companies appear to be moving away from COVID R&D.Assessing the clinical trial landscape for industry-sponsored trials shows that in 2022 the number of trial initiations decreased by 7%overall.However,when excluding COVID-19

178、 trials from this analysis,this reduces to a 4%decline,reflecting the industrys survival mode since 2021.“We have been seeing significant pipeline attrition as minor players have reallocated resources to other,more profitable indications from approximately 2021 onwards,”noted Datamonitor Healthcare

179、analysts Natasha Boliter and Charlotte Holmes.“This phenomenon is particularly encouraged by the speed of COVID-19 mutation,demanding annual,variant-specific vaccines,and the excellent efficacy results(exceeding 90%)of currently marketed assets.However,we are also seeing pipeline discontinuations fr

180、om larger vaccine manufacturers.This was heralded by Sanofi in 2021,which suspended development of its own mRNA vaccine,despite reporting positive Phase I/II results,stating that the program was no longer commercially viable given the dominance of the other mRNA vaccines.”(see Exhibit 3).There is un

181、certainty even for giants in the COVID-19 vaccine industry.Pfizer,for example,is encountering constraints in the COVID-19 market,with predicted revenues for 2023 less than 60%of the preceding year.“In light of this,Pfizer has announced an enterprise-wide cost realignment program in response to the u

182、npredictable demand caused by the transition from the government-sponsored pandemic phase to the privately or individually funded endemic phase,”Boliter and Holmes highlighted.“Currently,it is uncertain what this will mean for its pan-respiratory programs or its future seasonal,variant-specific vacc

183、ines.”There is still R&D interest in COVID,but the pipeline today consists of mainly next-generation mAbs,variant-specific adaptations of currently marketed vaccines and the pan-respiratory combination vaccines.Looking ahead into the first half of 2024,AstraZeneca is expected to announce efficacy da

184、ta from the Phase I/III SUPERNOVA study for its next-generation mAb AZD3152.Similarly,Invivyd is expecting primary endpoint data from the Phase III CANOPY trial of its next-generation mAb VYD222 by early 2024.Biopharma Embraces New Markets And New Tech11December 2023 Copyright 2023 Pharma Intelligen

185、ce UK Limited,a Citeline company(Unauthorized photocopying prohibited)Generative AIArtificial intelligence was a buzzword in almost all panel discussions at the November 2023 BIO-Europe conference.There is a lot of promise,but also a lot of confusion about best uses.The speed of technology developme

186、nt in AI is outpacing biopharma.Generative AI,building upon advances in deep learning,is both a promising and a concerning technology.“If harnessed securely and ethically,leveraging multi-modal data,such as text,images,and videos,generative AI can help pharmaceutical companies identify unmet clinica

187、l needs and expedite clinical planning and execution strategies,”said Luca Parisi,Citelines director of clinical analytics and data science.In both drug discovery and repurposing,generative AI can play a role in respectively devising novel molecules and elucidating relationships that may inform drug

188、 repositioning.“Generative AI-powered drug repurposing efforts may include both approved drugs in certain indications and help in capitalizing on those drugs that did not make it through Phase II studies in some indications but could be better suited for treating other indications,”Parisi said.He al

189、so highlighted the potential of leveraging real-world data,especially electronic health records and medical images.Here,generative AI“can help to titrate treatments on a subject-specific basis,accelerating the transformational paradigm of personalized medicine and the impact it can bring to providin

190、g subject-specific,lifesaving or life-enhancing treatments faster.”Despite the potential uses and clear excitement around generative AI tools,there are challenges for using the technology in a health care setting.“It is crucial to ensure HIPAA,GDPR(where applicable),and GxP compliance by design,thus

191、 leveraging appropriate infrastructure and technologies to guarantee that data security and confidentiality,and patient privacy are adhered to,”Parisi warned.“Furthermore,considering the scale of the data required to train such large generative AI models,Biopharma Embraces New Markets And New TechEx

192、hibit 3:Worldwide Sales For COVID-19 Treatments And Prophylaxis8|In Vivo|December 2023December 2023|In Vivo|9 OUTLOOK OUTLOOKDrug/DeveloperClinical Trial Analysts Comments patritumab deruxtecan/Daiichi SankyoPhase III HERTHENA-Lung02The HER3-directed ADC patritumab deruxtecan is the first anti-HER3

193、monoclonal antibody in development for the treatment of NSCLC.Daiichi Sankyo is investigating patritumab deruxtecan in the Phase III HERTHENA-Lung02 trial in patients with EGFR-mutated advanced or metastatic NSCLC whose disease has progressed following treatment with a third-generation EGFR inhibito

194、r.Tagrisso,a third-generation EGFR inhibitor,is estimated to capture 6070%of the first-line advanced or metastatic EGFR-positive NSCLC market,and a standard of care treatment following disease progression is yet to be determined.Typically,patients are not retreated with EGFR inhibitor monotherapy,me

195、aning chemotherapy is often the choice of treatment and these patients are lacking an active and tolerable targeted treatment.Opdivo/BMSPhase III CheckMate 9DXTesting Opdivo in the adjuvant setting for the treatment of early-stage HCC.Currently,early-stage HCC patients are primarily treated with liv

196、er transplants or surgical resection,or with locoregional therapies if they are not candidates for surgery.Imfinzi/AstraZenecaPhase III EMERALD-2Testing Imfinzi with or without bevacizumab as an adjuvant therapy in patients with HCC who are at high risk of recurrence after curative hepatic resection

197、 or ablation.As with Opdivo,there is an unmet need for an efficacious but tolerable therapy for these early-stage HCC patients.Closing The Door On COVID?For many people,the pandemic is being placed firmly in the past as new worries take precedent the challenging economic climate,upcoming election ye

198、ars and tougher regulation,as a few examples.However,winter of 2023 will be a key test for countries that have seen declining levels of COVID-19 following successful vaccine programs.The biopharma sector is demonstrating a mixed response,with some companies investing in advanced vaccine options whil

199、e others step away from COVID R&D.With the Omicron variant now the dominant strain globally,accounting for 99%of new cases in the US and Europe,efficacy against this strain is paramount to long-term commercial potential.So far,Pfizer/BioNTechs Comirnaty and Modernas Spikevax have shown the most robu

200、st efficacy data against the Omicron variant,with vaccine efficacy of 90%against hospitalization and death after a third booster dose,though protection wanes considerably after four months.Inactivated vaccines have played a crucial role in primary vaccination series in China,India,Russia,and other e

201、merging markets.However,as domestically produced vectored,protein subunit and recently mRNA vaccines reach emerging markets,inactivated vaccines are expected to progressively lose market share.Many pharma companies appear to be moving away from COVID R&D.Assessing the clinical trial landscape for in

202、dustry-sponsored trials shows that in 2022 the number of trial initiations decreased by 7%overall.However,when excluding COVID-19 trials from this analysis,this reduces to a 4%decline,reflecting the industrys survival mode since 2021.“We have been seeing significant pipeline attrition as minor playe

203、rs have reallocated resources to other,more profitable indications from approximately 2021 onwards,”noted Datamonitor Healthcare analysts Natasha Boliter and Charlotte Holmes.“This phenomenon is particularly encouraged by the speed of COVID-19 mutation,demanding annual,variant-specific vaccines,and

204、the excellent efficacy results(exceeding 90%)of currently marketed assets.However,we are also seeing pipeline discontinuations from larger vaccine manufacturers.This was heralded by Sanofi in 2021,which suspended development of its own mRNA vaccine,despite reporting positive Phase I/II results,stati

205、ng that the program was no longer commercially viable given the dominance of the other mRNA vaccines.”(see Exhibit 3).There is uncertainty even for giants in the COVID-19 vaccine industry.Pfizer,for example,is encountering constraints in the COVID-19 market,with predicted revenues for 2023 less than

206、 60%of the preceding year.“In light of this,Pfizer has announced an enterprise-wide cost realignment program in response to the unpredictable demand caused by the transition from the government-sponsored pandemic phase to the privately or individually funded endemic phase,”Boliter and Holmes highlig

207、hted.“Currently,it is uncertain what this will mean for its pan-respiratory programs or its future seasonal,variant-specific vaccines.”There is still R&D interest in COVID,but the pipeline today consists of mainly next-generation mAbs,variant-specific adaptations of currently marketed vaccines and t

208、he pan-respiratory combination vaccines.Looking ahead into the first half of 2024,AstraZeneca is expected to announce efficacy data from the Phase I/III SUPERNOVA study for its next-generation mAb AZD3152.Similarly,Invivyd is expecting primary endpoint data from the Phase III CANOPY trial of its nex

209、t-generation mAb VYD222 by early 2024.Generative AIArtificial intelligence was a buzzword in almost all panel discussions at the November 2023 BIO-Europe conference.There is a lot of promise,but also a lot of confusion about best uses.The speed of technology development in AI is outpacing biopharma.

210、Generative AI,building upon advances in deep learning,is both a promising and a concerning technology.“If harnessed securely and ethically,leveraging multi-modal data,such as text,images,and videos,generative AI can help pharmaceutical companies identify unmet clinical needs and expedite clinical pl

211、anning and execution strategies,”said Luca Parisi,Citelines director of clinical analytics and data science.In both drug discovery and repurposing,generative AI can play a role in respectively devising novel molecules and elucidating relationships that may inform drug repositioning.“Generative AI-po

212、wered drug repurposing efforts may include both approved drugs in certain indications and help in capitalizing on those drugs that did not make it through Phase II studies in some indications but could be better suited for treating other indications,”Parisi said.He also highlighted the potential of

213、leveraging real-world data,especially electronic health records and medical images.Here,generative AI“can help to titrate treatments on a subject-specific basis,accelerating the transformational paradigm of personalized medicine and the impact it can bring to providing subject-specific,lifesaving or

214、 life-enhancing treatments faster.”Despite the potential uses and clear excitement around generative AI tools,there are challenges for using the technology in a health care setting.“It is crucial to ensure HIPAA,GDPR(where applicable),and GxP compliance by design,thus leveraging appropriate infrastr

215、ucture and technologies to guarantee that data security and confidentiality,and patient privacy are adhered to,”Parisi warned.“Furthermore,considering the scale of the data required to train such large generative AI models,appropriate analyses to detect and minimize biases and ensure representativen

216、ess in the underlying data are of paramount importance to provide clinically relevant,accurate and reliable recommendations to design more recruitable,diverse,inclusive clinical trials,and inform operational workflows throughout the clinical trial lifecycle objectively.”The key challenges ahead towa

217、rds a fruitful,sustainable adoption of generative AI tools are:1.data quality,given the scale of the data required;2.achieving a seamless integration of such advanced technologies in clinical workflows;3.tackling ethical considerations by design;4.ensuring replicability and reproducibility at all st

218、ages;5.clinical validation of the outputs derived from these technologies.The main expectation for the biopharma sector is to accelerate the continuum of the drug development pipeline and clinical trial lifecycle,increasing both time and cost savings.A Health Care Metamorphosis Biopharma is on the e

219、dge of a new era driven by the need to replenish pipelines and the evolution of technology.In 2024,the sector will see 70 key launches from around 65 drug brands.A notable proportion of these launches have the potential to shift treatment practices.AstraZenecas Imfinzi is just one example,with five

220、label expansions expected in the coming year.After a period of easy fund raising and busy deal-making in 2020-2021,tough times have hit the sector.But there is positivity for the volume of M&A deals to rise again,even if the financial markets do not bounce back as quickly as some might hope in the c

221、oming 12 months.Regulatory changes will have an impact from 2024 into the coming few years,in the form of both intentional and unintended consequences.Astellass Hardiman summarized the state of the sector:“We have seen a myriad of challenges over the course of time.As a testament to our industry,we

222、always overcome these I am confident and optimistic that we can again.”20204.46396.38105.24239.25530.43226.76324.06722.71722.02720212022202320242025202620272028Exhibit 3:Worldwide Sales For COVID-19 Treatments And ProphylaxisSource:Evaluate Pharma 12December 2023 Copyright 2023 Pharma Intelligence U

223、K Limited,a Citeline company(Unauthorized photocopying prohibited)appropriate analyses to detect and minimize biases and ensure representativeness in the underlying data are of paramount importance to provide clinically relevant,accurate and reliable recommendations to design more recruitable,divers

224、e,inclusive clinical trials,and inform operational workflows 2020 2021 throughout the clinical trial lifecycle objectively.”The key challenges ahead towards a fruitful,sustainable adoption of generative AI tools are:1.data quality,given the scale of the data required;2.achieving a seamless integrati

225、on of such advanced technologies in clinical workflows;3.tackling ethical considerations by design;4.ensuring replicability and reproducibility at all stages;5.clinical validation of the outputs derived from these technologies.The main expectation for the biopharma sector is to accelerate the contin

226、uum of the drug development pipeline and clinical trial lifecycle,increasing both time and cost savings.A Health Care Metamorphosis Biopharma is on the edge of a new era driven by the need to replenish pipelines and the evolution of technology.In 2024,the sector will see 70 key launches from around

227、65 drug brands.A notable proportion of these launches have the potential to shift treatment practices.AstraZenecas Imfinzi is just one example,with five label expansions expected in the coming year.After a period of easy fund raising and busy deal-making in 2020-2021,tough times have hit the sector.

228、But there is positivity for the volume of M&A deals to rise again,even if the financial markets do not bounce back as quickly as some might hope in the coming 12 months.Regulatory changes will have an impact from 2024 into the coming few years,in the form of both intentional and unintended consequen

229、ces.Astellass Hardiman summarized the state of the sector:“We have seen a myriad of challenges over the course of time.As a testament to our industry,we always overcome these I am confident and optimistic that we can again.”Biopharma Embraces New Markets And New Tech13January 2023 Copyright 2023 Pha

230、rma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)As 2023 began,biopharmaceutical industry observers predicted an increase in both merger-and-acquisition activity as well as the return of some larger transactions similar to the occasional mega-mergers seen before th

231、e COVID-19 pandemic.During the first quarter,this expectation was realized as Pfizer sought to bolster its cancer biologics portfolio with the$43bn acquisition of the antibody-drug conjugate specialist Seagen.However,an ensuing wave of larger M&A deals did not arrive and M&A activity slowed down dur

232、ing the second and third quarters in terms of aggregate value.But in recent years the fourth quarter has seen some of the biggest M&As,such as Amgens$27.8bn acquisition of Horizon in December 2022 and CSLs$12.2bn takeout of Vifor Pharma in December 2021,each the years largest M&A deal by dollar valu

233、e.So far,two of 2023s five largest M&A deals based on upfront US dollar value have occurred since 1 October,with the Bristol Myers Squibb/Mirati and Roche/Televant transactions.Still,the$10.8bn buyout by Merck&Co.of Prometheus in April is the only deal other than Pfizer/Seagen in the double-digit bi

234、llions 2023 to date has seen a continuance of the biopharma sectors preference for bolt-on deal-making.With 18 biopharma M&A transactions with upfront values of$1bn or more as of early The Biggest M&A Announcements Of 2023 Show Deals Are Getting BiggerBy Joseph Haas,Senior WriterExecutive SummaryM&A

235、 activity in 2023 began with Marchs$43bn mega-deal for Seagen,but only one eight-figure takeout has occurred since.Still,the values are higher overall than seen in 2022 and might indicate a gradual return to larger deals.14December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline compan

236、y(Unauthorized photocopying prohibited)The Biggest M&A Announcements Of 2023 Show Deals Are Getting BiggerNovember,2023 tops the 16 recorded in 2020 and 17 seen in 2022,and is on pace to surpass the 19 such deals seen in both 2021 and also 2019.That year just before the pandemic,however,saw two mega

237、-mergers on a scale greater than any deals seen since:the$74bn BMS/Celgene takeout and the$63bn AbbVie/Allergan combination.But that was a rarity:2019 was the only the year in which two deals valued at$30bn or more were completed since 2009,when the sector produced three such transactions Pfizer/Wye

238、th,Merck/Schering Plough and Roche acquiring the remainder of Genentech.Deal size is trending upward,however.The five biggest deals of 2023 so far are mammoth in proportion to 2022s activity,in which there were two eight-digit expenditures(see Exhibit 1).Cancer remains a perennial driver of deal-mak

239、ing for biopharma,while gastrointestinal disease is an area of high competition among numerous companies and mechanisms of action.Meanwhile,outside the five largest buyouts,2023 has seen growing competition in another burgeoning space obesity/weight-loss Eli Lilly and Novo Nordisk engaged in deal-ma

240、king as leverage against one another and to solidify their positions as the two major players in that arena.1.Pfizer/Seagen($43bn)Facing a significant patent cliff,Pfizer acquired both revenue-generating products and new R&D capabilities with its proposed acquisition of Seagen in a deal slated to cl

241、ose by the end of 2023.Seagens four approved drugs the ADCs Adcetris(brentuximab vedotin)for hematological malignancies,Tivdak(tisotumab vedotin)for cervical cancer and Padcev(enfortumab vedotin)for bladder cancer along with the breast cancer drug Tukysa(tucatinib)are projected to bring Pfizer$10bn

242、in revenue by 2030.If those projections prove accurate,the proceeds will get Pfizer a significant part of the way to the$25bn in new product revenue it said it hoped to bring in to offset the impact of patent expirations of products like the breast cancer drug Ibrance(palbociclib)and a prostate canc

243、er therapy partnered with Astellas,Xtandi(enzalutamide).During an investor Exhibit 1:Five Biggest M&A Deals Of 2023&2022 BUSINESS26|In Vivo|December 2023December 2023|In Vivo|27BY JOSEPH HAAS,SENIOR WRITERAs 2023 began,biopharmaceutical industry observers predicted an increase in both merger-and-acq

244、uisition activity as well as the return of some larger transactions similar to the occasional mega-mergers seen before the COVID-19 pandemic.During the first quarter,this expectation was realized as Pfizer sought to bolster its cancer biologics portfolio with the$43bn acquisition of the antibody-dru

245、g conjugate specialist Seagen.However,an ensuing wave of larger M&A deals did not arrive and M&A activity slowed down during the second and third quarters in terms of aggregate value.But in recent years the fourth quarter has seen some of the biggest M&As,such as Amgens$27.8bn acquisition of Horizon

246、 in December 2022 and CSLs$12.2bn takeout of Vifor Pharma in December 2021,each the years largest M&A deal by dollar value.So far,two of 2023s five largest M&A deals based on upfront US dollar value have occurred since 1 October,with the Bristol Myers Squibb/Mirati and Roche/Televant transactions.St

247、ill,the$10.8bn buyout by Merck&Co.of Prometheus in April is the only deal other than Pfizer/Seagen in the double-digit billions 2023 to date has seen a continuance of the biopharma sectors preference for bolt-on deal-making.With 18 biopharma M&A transactions with upfront values of$1bn or more as of

248、early November,2023 tops the 16 recorded in 2020 and 17 seen in 2022,and is on pace to surpass the 19 such deals seen in both 2021 and also 2019.That year just before the pandemic,however,saw two mega-mergers on a scale greater than any deals seen since:the$74bn BMS/Celgene takeout and the$63bn AbbV

249、ie/Allergan combination.But that was a rarity:2019 was the only the year in which two deals valued at$30bn or more were completed since 2009,when the sector produced three such transactions Pfizer/Wyeth,Merck/Schering Plough and Roche acquiring the remainder of Genentech.Deal size is trending upward

250、,however.The five biggest deals of 2023 so far are mammoth in proportion to 2022s activity,in which there were two eight-digit expenditures(see Exhibit 1).Cancer remains a perennial driver of deal-making for biopharma,while gastrointestinal disease is an area of high competition among numerous compa

251、nies and mechanisms of action.Meanwhile,outside the five largest buyouts,2023 has seen growing competition in another burgeoning space obesity/weight-loss Eli Lilly and Novo Nordisk engaged in deal-making as leverage against one another and to solidify their positions as the two major players in tha

252、t arena.1.Pfizer/Seagen($43bn)Facing a significant patent cliff,Pfizer acquired both revenue-generating products and new R&D capabilities with its proposed acquisition of Seagen in a deal slated to close by the end of 2023.Seagens four approved drugs the ADCs Adcetris(brentuximab vedotin)for hematol

253、ogical malignancies,Tivdak(tisotumab vedotin)for cervical cancer and Padcev(enfortumab vedotin)for bladder cancer along with the breast cancer drug Tukysa(tucatinib)are projected to bring Pfizer$10bn in revenue by 2030.If those projections prove accurate,the proceeds will get Pfizer a significant pa

254、rt of the way to the$25bn in new product revenue it said it hoped to bring in to offset the impact of patent expirations of products like the breast cancer drug Ibrance(palbociclib)and a prostate cancer therapy partnered with Astellas,Xtandi(enzalutamide).During an investor briefing last December,Pf

255、izer execs said they were attempting to add$25bn in new product revenue through business development by 2030.Pfizer also said it decided to buy Seagen because it wanted to add ADCs to its portfolio both because biosimilar competition might be less likely to emerge and biologics have longer exemption

256、 from Medicare price negotiations under the 2022 Inflation Reduction Act.The mergers closure has been delayed by a review by the US Federal Trade Commission,but the recent settlement between the agency and Amgen has enabled that companys acquisition of Horizon to close,helping to ameliorate doubts a

257、bout whether Pfizer/Seagen might face heightened FTC scrutiny.2.Merck&Co./Prometheus($10.8bn)Merck made 2023s second-largest acquisition as of early November in a diversification play to acquire autoimmune disease-focused Prometheus for$10.8bn on 16 April.The New Jersey pharma agreed to pay$200 per

258、share for Prometheus,an 80%premium to the San Diego-based firms 10-day average trading price,and the transaction closed on 16 June.Merck sought to reduce its reliance on oncology and specifically its blockbuster anti-PD-1 agent Keytruda(pembrolizumab),which generated about 40%of the pharmas 2022 sal

259、es revenue,about five years ahead of expected biosimilar competition.The high price tag partly reflected the near-term earning potential of Prometheuss PRA023(now MK-7240),an anti-TL1A agent nearing Phase III in multiple IBD indications.Prometheuss R&D engine also was expected to enhance Mercks targ

260、et discovery and precision medicine capabilities in autoimmune disease.Mercks buyout of Prometheus may have been driven in part by a failed attempt to acquire Seagen.3.Biogen/Reata($7.3bn)On 28 July,Biogen agreed to pay$172.50 per share,a hefty 58%premium,to acquire Reata and its recently approved F

261、riedreichs ataxia(FA)drug Skyclarys(omaveloxelone),a predicted blockbuster.The transaction closed on 26 September.Dealing with generic competition to Tecfidera(dimethyl fumarate)and the failure of its Alzheimers drug Aduhelm(aducanumab),Biogen picked up a product that would increase its position in

262、rare diseases while adding a revenue-generator that might enable patience for the launch of its second Alzheimers drug partnered with Eisai,Leqembi(lecanemab),and amyotrophic lateral sclerosis drug Qalsody(tofersen).4.Roche/Televant($7.1bn)Roche agreed on 23 October to pay$7.1bn up front for Roivant

263、s subsidiary Televant,due to that companys TL1A antibody therapeutic,RVT-3101(formerly PF-06480605).Sanofi and Teva also have a TL1A inhibitor in development for IBD,creating a three-way competition by deep-pocketed commercial rivals.Roivant had only acquired the candidate months before from Pfizer,

264、in a deal that created the Televant spinout and gave Pfizer a 25%ownership stake.In a Phase IIb study,RVT-3101 has demonstrated better than the 30%remission and 50%response rates achieved by current treatments for ulcerative colitis.5.Bristol Myers Squibb/Mirati($4.8bn)BMS agreed to pay$4.8bn up fro

265、nt on 8 October to acquire San Diego-based Mirati,reportedly prevailing in a competitive bidding process that also included Sanofi.Bristols offer came in at$58 per share,a 52%premium to the biotechs 30-day average share price,and the deal also included a contingent value right worth up to$1bn tied t

266、o potential US Food and Drug Administration approval within seven years of deal closing for PRMT5 inhibitor MRTX1719.But the deals primary driver was Krazati(adagrasib),a KRAS inhibitor launched last December for previously treated KRASG12C-mutated non-small cell lung cancer(NSCLC).BMS said the prod

267、uct inhibitor would diversify its cancer portfolio,including Opdivo(nivolumab)and Yervoy(ipilimumab),while Miratis R&D pipeline would bring in additional anti-KRAS agents.M&A activity in 2023 began with Marchs$43bn mega-deal for Seagen,but only one eight-figure takeout has occurred since.Still,the v

268、alues are higher overall than seen in 2022 and might indicate a gradual return to larger deals.The Biggest M&A Announcements Of 2023 Show Deals Are Getting BiggerSource:Company filingsExhibit 1:Five Biggest M&A Deals Of 2023&2022Biogen/ReataPfizer/Global BloodRoche/TelevantBMS/Turning PointBMS/Mirat

269、iAmgen/Chemocentryx12345Pfizer/SeagenAmgen/HorizonPfizer/BiohavenMerck&Co./Prometheus$43bn$27.8bn$10.8bn$11.6bn$7.3bn$5.2bn$7.1bn$4.1bn$4.8bn$3.7bn2023202215December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)briefing last December,Pfiz

270、er execs said they were attempting to add$25bn in new product revenue through business development by 2030.Pfizer also said it decided to buy Seagen because it wanted to add ADCs to its portfolio both because biosimilar competition might be less likely to emerge and biologics have longer exemption f

271、rom Medicare price negotiations under the 2022 Inflation Reduction Act.The mergers closure has been delayed by a review by the US Federal Trade Commission,but the recent settlement between the agency and Amgen has enabled that companys acquisition of Horizon to close,helping to ameliorate doubts abo

272、ut whether Pfizer/Seagen might face heightened FTC scrutiny.2.Merck&Co./Prometheus($10.8bn)Merck made 2023s second-largest acquisition as of early November in a diversification play to acquire autoimmune disease-focused Prometheus for$10.8bn on 16 April.The New Jersey pharma agreed to pay$200 per sh

273、are for Prometheus,an 80%premium to the San Diego-based firms 10-day average trading price,and the transaction closed on 16 June.Merck sought to reduce its reliance on oncology and specifically its blockbuster anti-PD-1 agent Keytruda(pembrolizumab),which generated about 40%of the pharmas 2022 sales

274、 revenue,about five years ahead of expected biosimilar competition.The high price tag partly reflected the near-term earning potential of Prometheuss PRA023(now MK-7240),an anti-TL1A agent nearing Phase III in multiple IBD indications.Prometheuss R&D engine also was expected to enhance Mercks target

275、 discovery and precision medicine capabilities in autoimmune disease.Mercks buyout of Prometheus may have been driven in part by a failed attempt to acquire Seagen.3.Biogen/Reata($7.3bn)On 28 July,Biogen agreed to pay$172.50 per share,a hefty 58%premium,to acquire Reata and its recently approved Fri

276、edreichs ataxia(FA)drug Skyclarys(omaveloxelone),a predicted blockbuster.The transaction closed on 26 September.Dealing with generic competition to Tecfidera(dimethyl fumarate)and the failure of its Alzheimers drug Aduhelm(aducanumab),Biogen picked up a product that would increase its position in ra

277、re diseases while adding a revenue-generator that might enable patience for the launch of its second Alzheimers drug partnered with Eisai,Leqembi(lecanemab),and amyotrophic lateral sclerosis drug Qalsody(tofersen).4.Roche/Televant($7.1bn)Roche agreed on 23 October to pay$7.1bn up front for Roivants

278、subsidiary Televant,due to that companys TL1A antibody therapeutic,RVT-3101(formerly PF-06480605).Sanofi and Teva also have a TL1A inhibitor in development for IBD,creating a three-way competition by deep-pocketed commercial rivals.Roivant had only acquired the candidate months before from Pfizer,in

279、 a deal that created the Televant spinout and gave Pfizer a 25%ownership stake.In a Phase IIb study,RVT-3101 has demonstrated better than the 30%remission and 50%response rates achieved by current treatments for ulcerative colitis.5.Bristol Myers Squibb/Mirati($4.8bn)BMS agreed to pay$4.8bn up front

280、 on 8 October to acquire San Diego-based Mirati,reportedly prevailing in a competitive bidding process that also included Sanofi.Bristols offer came in at$58 per share,a 52%premium to The Biggest M&A Announcements Of 2023 Show Deals Are Getting Bigger16December 2023 Copyright 2023 Pharma Intelligenc

281、e UK Limited,a Citeline company(Unauthorized photocopying prohibited)the biotechs 30-day average share price,and the deal also included a contingent value right worth up to$1bn tied to potential US Food and Drug Administration approval within seven years of deal closing for PRMT5 inhibitor MRTX1719.

282、But the deals primary driver was Krazati(adagrasib),a KRAS inhibitor launched last December for previously treated KRASG12C-mutated non-small cell lung cancer(NSCLC).BMS said the product inhibitor would diversify its cancer portfolio,including Opdivo(nivolumab)and Yervoy(ipilimumab),while Miratis R&

283、D pipeline would bring in additional anti-KRAS agents.The Biggest M&A Announcements Of 2023 Show Deals Are Getting Bigger17January 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)At the midway point of 2023,dealmaking for big pharma had roar

284、ed back to life following relative austerity in the previous two years,as credit became harder to come by,interest rates spiked,and lenders tightened up in a challenging and volatile market.Huge deals penned by COVID-rich Pfizer(Seagen:$43bn)and Merck&Co(Prometheus Biosciences:$10.8bn)showed that th

285、e worlds biggest companies still had an appetite for dealmaking,and would put up the cash dipping into their reserves,if not going directly to a lender in order to placate investors spooked by patent cliffs.“I know a lot of companies are hurting because of the higher interest rates,”acknowledged Hik

286、mas recently instated CEO,Riad Mishlawi,speaking in November 2023.On the side of the aisle where Hikma mainly operates,perhaps for this very reason,headline-grabbing deals for generic and biosimilars have dipped in 2023,following a fairly fruitful 2022.A colorful prior year included Biocon Biologics

287、 splashing out more than$3bn for longtime partner Viatris biosimilars business;Fresenius Kabis 495m purchase of an initial 55%stake in Insud Pharmas biopharma unit,mAbxience;and Hikma acquiring US sterile injectables specialist Custopharm for up to$425m.Meanwhile,a landmark special purpose acquisiti

288、on company(SPAC)merger delivered Big Pharma Shouts,Generics And Biosimilars Whisper:M&A In 2023By Dean Rudge,Deputy EditorExecutive Summary“A lot of companies are hurting because of the higher interest rates,”one major CEO observed recently,summing up a year which saw little headline-grabbing news o

289、n the M&A front for generic and biosimilar sponsors.18December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)Big Pharma Shouts,Generics And Biosimilars Whisper:M&A In 2023a much-desired public listing for Alvotech;and Novartis looking to t

290、ighten its focus on innovative assets announced that it was separating its Sandoz generics and biosimilars unit into a publicly traded,standalone company.Viatris OffloadsIn a similar vein to Novartis/Sandoz,Viatris clearly-mapped-out desire to turn its attention to a select group of mostly novel ass

291、ets provided for one of the years most significant deals.Viatris in October moved to offload four businesses that it has deemed unfit for the next phase of its strategic roadmap,including its six-facility-strong active pharmaceutical ingredients operations in India,in the process bringing in what it

292、 said was the companys original total target in value terms.The for-sale API business is set to become a part of privately held Indian player IQuest Enterprises,encompassing three manufacturing sites and a R&D lab in Hyderabad,three manufacturing sites in Vizag,and third-party API sales.IQuest is co

293、ntrolled by Nimmagadda Prasad,the Indian industrialist who previously founded Matrix Laboratories.In 2006/07,the former Mylan company closed deals for a majority stake in Matrix,swallowing up the remainder two years later.In the wake of closing the Biocon-biosimilars-deal,Viatris also confirmed defi

294、nitive agreements for its Womens Healthcare business and commercialization rights in certain non-core markets that were acquired as part of Mylans merger with Upjohn.Meanwhile,Viatris received an offer to divest substantially all of its OTC business,under which it will hang on to two of its powerhou

295、se brands,Viagra(sildenafil)and Dymista(azelastine/fluticasone).Including the previous biosimilars sale,Viatris believes it is in line to bag up to$6.94bn in gross proceeds.Bolt-On Deals In a year marked by a paucity of big deals,a small amount of companies have in some cases found the strategic rat

296、ionale to throw their respective lots in together.Meanwhile,other generic and biosimilar players hamstrung by a challenging business environment favoured bolt-on and tuck-in type deals,looking to augment already built-up areas or geographies of their businesses.One of the largest players in the sect

297、or,Dr Reddys Laboratories,did just this,acquiring the US prescription generics portfolio of Australias Mayne Pharma in a deal worth at least$90m.Generating sales of$111m in Maynes 2021/21 financial year,the portfolio included approximately 45 commercial products,four pipeline products and 40 approve

298、d non-marketed products,most notably a hormonal vaginal ring and a birth control pill,as well as a cardiovascular product.Meanwhile,Hikma acquired a selection of assets from bankrupt Akorn in July for as similar purchase price,$98m,including manufacturing equipment and portfolio and pipeline product

299、s that will support the companys businesses in the US.The Future For Stada As 2023 ticks over into 2024,one major deal to keep eyes on is the fate of German generics and biosimilars giant Stada.19December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying

300、 prohibited)Earlier this year,the companys owners,Bain Capital and Cinven,were revealed to be mulling the possibility of selling Stada,the companys CEO Peter Goldschmidt said.Acknowledgment of a potentially major deal came almost exactly six years to the day since the private equity duo took control

301、 of the Germany-based,European generics and biosimilars giant.Goldschmidts comments,made to the German Press Agency,followed reports in Bloomberg that Bain and Cinven were considering a potential sale valuing Stada at around 10bn.Reports included the potential to conduct an initial public offering f

302、or the German firm.Goldschmidt,who recently celebrated five years in his current role,said he did not expect a decision to be made before 2024 and insisted that Stadas“financial investors have no pressure to sell.”However,he added,“What speaks in favour of a sale process is that it is common for fin

303、ancial investors to exit after five to six years,”he reasoned.Big Pharma Shouts,Generics And Biosimilars Whisper:M&A In 202320January 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)One of the more prominent arguments against the Medicare dr

304、ug price negotiation program is that by limiting the number of years that products can be marketed before price caps are imposed,the scheme discourages development of additional indications.New research on the 10 drugs selected for the initial round of negotiation both reinforces and complicates tha

305、t narrative.Research and development spending to date for most of the 10 drugs is well above the often-cited$2.5bn industry benchmark for R&D,according to an analysis conducted by health care research and advisory services firm ATI Advisory.But most of those studies were conducted well before the ni

306、ne-year cutoff on market pricing that the new Medicare program would impose.Spending estimates for six of the drugs were$3.5bn or above and ranged up to$7.8bn for Bayer/Johnson&Johnsons anticoagulant Xarelto.For most of the drugs,the greatest share of R&D spending came after approval,averaging 61%ac

307、ross all products,according to the study.Boehringer Ingelheim/Eli Lillys antidiabetic Jardiance and Novartis heart failure drug Entresto were the only two products in the analysis with spending that was higher in the pre-approval space,but the difference was minimal.The estimates were derived from p

308、ublicly available clinical trial information.The researchers did not estimate R&D spending for Novo Nordisks Novolog insulin and Amgens Medicare Price Setting And The Value Of Post-Approval R&D SpendingBy Cathy Kelly,Senior EditorExecutive SummaryWill scrutiny by the Centers for Medicare and Medicai

309、d Services eventually lead to shifts in investment away from improving older drugs toward developing new products?21December 2023 Copyright 2023 Pharma Intelligence UK Limited,a Citeline company(Unauthorized photocopying prohibited)Medicare Price Setting And The Value Of Post-Approval R&D Spendingan

310、ti-inflammatory Enbrel because their development preceded modern clinical trial reporting standards.The study is meant to shed light on the kind of information that manufacturers of the selected drugs were required to submit to the Centers for Medicare and Medicaid Services in October to facilitate

311、the negotiation process.CMS will look at R&D spending to assess the degree to which developers have recouped their investment.The agency announced the list of 10 drugs in late August.Anna Kaltenboeck,head of ATIs prescription drug reimbursement practice,discussed the findings and how the data might

312、be received by CMS in an interview.“We were struck by how high some of the spending was,it was pretty remarkable.And when we dug deeper we found that it is split in this way,”she said.“Part of the reason we created this report is that the negotiations are going to be behind closed doors but we wante

313、d to create some sort of benchmark to give people a feel for the magnitude of the numbers that CMS might be seeing once they get these submissions,and also to interpret them.”She also pointed out that although R&D spending might look higher than is widely understood,global sales for each of the prod

314、ucts on the list are greater than the expenditures by orders of magnitude.Therefore,there would be no question in CMS mind as to whether companies had recouped their investment,Kaltenboeck said.All But One Drug On The List Added Indications Post-ApprovalKaltenboeck observed there are important diffe

315、rences in the nature of R&D spending pre-and post-approval.“When youre talking about Exhibit 1:A Strong Return On InvestmentDecember 2023|In Vivo|85 POLICY®ULATION84|In Vivo|December 2023 POLICY®ULATIONCMS will look at R&D spending to assess the degree to which developers have recouped their i

316、nvestment.The agency announced the list of 10 drugs in late August.Anna Kaltenboeck,head of ATIs prescription drug reimbursement practice,discussed the findings and how the data might be received by CMS in an interview.“We were struck by how high some of the spending was,it was pretty remarkable.And

317、 when we dug deeper we found that it is split in this way,”she said.“Part of the reason we created this report is that the negotiations are going to be behind closed doors but we wanted to create some sort of benchmark to give people a feel for the magnitude of the numbers that CMS might be seeing o

318、nce they get these submissions,and also to interpret them.”She also pointed out that although R&D spending might look higher than is widely understood,global sales for each of the products on the list are greater than the expenditures by orders of magnitude.Therefore,there would be no question in CM

319、S mind as to whether companies had recouped their investment,Kaltenboeck said.Exhibit 1:A Strong Return On InvestmentGross sales figures do not include rebatesExhibit 2:Medicare Gross Spend Eclipses Sales For Many ProductsGross sales figures do not include rebates$4.3bn$57bn$14.3bn$15.8bn$36.8bn$54.

320、1bn$18.3bn$54.8bn$54.3bn$4.8bn$5.2bn$5.3bn$2.1bn$3.5bn$7.8bn$1.4bnEliquisEntrestoFarxigaImbruvicaJanuviaJardianceStelaraXarelto$5bnEstimateed Total R&D Spend for DrugGlobal Lifetime Sales$10bn$15bn$20bn$25bn$30bn$35bn$40bn$45bn$50bn$55bn$60bn22December 2023 Copyright 2023 Pharma Intelligence UK Limi

321、ted,a Citeline company(Unauthorized photocopying prohibited)the R&D work that you have to do before a drug comes to market,its riskier because theres always the possibility that you end up with zero revenue,”she noted.After approval,there is less risk because developers are already fairly familiar w

322、ith the drug and its target audience.Post-approval R&D work can satisfy postmarket commitments from the US Food and Drug Administration.It also includes market expansion efforts.“Some of this is adding more indications and in a lot of instances,youll see companies doing clinical studies not so much

323、for the FDAs benefit but actually for the benefit of the payers,to ensure they can get coverage on formulary to demonstrate their value.And then you also have studies to support reformulation of the product at later stages of life,so you sell more of the drug,”Kaltenboeck explained.“These tend to be

324、 big studies,which is a major cost driver and thats a lot of where you see those essentially benchmark costs going up in the postapproval phase,”she noted.For example,Bristol Myers Squibbs antidiabetic Farxiga“has added some new indications recently that puts it into the heart failure”space.“Its a s

325、trategic decision theyre making”to either expand their market share or ensure it stays where it is.All but two of the drugs,Mercks antidiabetic Januvia and Novolog,added at least one indication after initial approval.Johnson&Johnsons antiinflammatory Stelara added five indications.And other drugs ha

326、ve additional indications in the works.Boehringer Ingelheim and Lilly announced 22 September that the FDA had approved a major new indication in chronic kidney disease for Jardiance.Exhibit 2:Medicare Gross Spend Eclipses Sales For Many ProductsDecember 2023|In Vivo|85 POLICY®ULATION84|In Vivo|De

327、cember 2023 POLICY®ULATIONCMS will look at R&D spending to assess the degree to which developers have recouped their investment.The agency announced the list of 10 drugs in late August.Anna Kaltenboeck,head of ATIs prescription drug reimbursement practice,discussed the findings and how the data m

328、ight be received by CMS in an interview.“We were struck by how high some of the spending was,it was pretty remarkable.And when we dug deeper we found that it is split in this way,”she said.“Part of the reason we created this report is that the negotiations are going to be behind closed doors but we

329、wanted to create some sort of benchmark to give people a feel for the magnitude of the numbers that CMS might be seeing once they get these submissions,and also to interpret them.”She also pointed out that although R&D spending might look higher than is widely understood,global sales for each of the

330、 products on the list are greater than the expenditures by orders of magnitude.Therefore,there would be no question in CMS mind as to whether companies had recouped their investment,Kaltenboeck said.One of the more prominent arguments against the Medicare drug price negotiation program is that by li

331、miting the number of years that products can be marketed before price caps are imposed,the scheme discourages development of additional indications.New research on the 10 drugs selected for the initial round of negotiation both reinforces and complicates that narrative.Research and development spend

332、ing to date for most of the 10 drugs is well above the often-cited$2.5bn industry benchmark for R&D,according to an analysis conducted by health care research and advisory services firm ATI Advisory.But most of those studies were conducted well before the nine-year cutoff on market pricing that the

333、new Medicare program would impose.Spending estimates for six of the drugs were$3.5bn or above and ranged up to$7.8bn for Bayer/Johnson&Johnsons anticoagulant Xarelto.For most of the drugs,the greatest share of R&D spending came after approval,averaging 61%across all products,according to the study.Boehringer Ingelheim/Eli Lillys antidiabetic Jardiance and Novartis heart failure drug Entresto were