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1、Pharma R&D Annual Review 2022 Supplement:New Active Substances Launched During 2021Discover more at: Paper2IntroductionFollowing on from our review of trends in the current pharmaceutical R&D pipeline (download the report for free),this supplement takes a look at the industrys success stories of 202

2、1 the drugs which were launched onto the market for the first time during the year.Our survey focuses exclusively on new active substances(NASs):new chemical or biological entities where the active ingredient had received no prior approval for human use.This would also include vaccines with novel an

3、tigenic components.As such,this list represents a subset of all the first launches which Pharmaprojects reported during 2021,and excludes an additional 75 first drug launches of reformulated or non-NAS moieties,biosimilars,and imaging agents.So,to continue with our travel-based theme this year,these

4、 are drugs which remembered their passports,tickets,and vaccine certificates,boarded the plane for their flight through clinical development,touched down safely,and have now successfully completed their journey and arrived at their chosen destination.Travel was one of the pleasures in life which we

5、had previously taken for granted that was most affected by the COVID-19 pandemic over the past two years.Whereas usually,one could board a plane at the drop of a hat and be in foreign climes by teatime,for much of 2020 and 2021,international travel was completely out of the question.Indeed,during lo

6、ckdowns,in the UK at least,we were only permitted to leave our homes for essential food buying or our once-daily permitted bout of exercise.As our worlds essentially shrank to the size of our living rooms,somehow,drugs continued on their journeys through research and development.In the first part of

7、 this years Pharma R&D Review,we saw how little the pharma industry seems to have been perturbed by arguably the biggest global crisis of modern times.Pipelines continued to grow,new companies sprang up,and,after an initial readjustment,clinical trials continued.At the same time,an unprecedented eff

8、ort was diverted to tackling a completely new disease with extreme urgency.Having responded so quickly to altered circumstances through 2020,it seems to have largely been business as usual for pharma in 2021.But,with a record-breaking and expectation-confounding number of new drugs launched during t

9、he first year of the pandemic,surely the delivery of new medicines onto the market must have taken some kind of hit in 2021?In this report,we will examine in detail the numbers,types,and novelty of the drugs which,in the last calendar year,successfully completed their development journeys,and are no

10、w sitting back and relaxing on their deckchairs,sipping a pia colada and basking in the sunshine of success.Lets start by taking in the view of the full list of NASs which were launched across the year just passed.397 New Active Substance LaunchesPharma defies the pandemic to go supersonicOnce again

11、,the pharma industry has confounded its critics and surpassed expectations.After setting a new record for drug launches in 2020 with 82 NASs,somehow,that record has been smashed yet again.2021 saw 97 NASs across 95 new products(two launches were combination products containing two NASs apiece).So,de

12、spite all the disruption to trials,supply chains,and launch plans;despite all the sudden diversions of resources which the pandemic precipitated;despite everything,pharma landed a record number of its travellers in the new territory.A sound barrier smashing result,to be sure.As Figure 1 shows,rather

13、 than being hampered by COVID,the past two years were by some distance the best ever,with 2021s tally being almost double that seen only two years earlier.Indeed,barring a couple of wobbles,its pretty clear that the overall trend is soaring inexorably upwards.As usual,we must caveat the data by noti

14、ng that segmenting NAS launches by calendar year is a somewhat arbitrary way of counting NAS success,since a few just missing 362929222628263126353637375743344761497484002143111181311637770813102030405060708090100200120022003200420052006200720082009201020112012201320142015201620172018201920202021NUM

15、BER OF NAS LAUNCHESYEARNASVaccineFIGURE 1:Number of NAS launches by year,200121Source:Pharmaprojects,February 20224the end of one year and spilling over into the next might depress the first years figures while boosting the seconds.But that certainly didnt happen from 2020 to 2021.Might we be headin

16、g for pharma breaching the three-figure barrier in annual delivery of new drugs sometime soon?Its undoubtedly the case that COVID has stimulated,rather than hampered,this figure;of the 13 vaccines included in the total this year,11 are against the novel coronavirus.But it is encouraging to see that

17、the non-vaccine number of NASs is also overtaking last years total in the fast lane.Stripping out the vaccine figures,we can take a better look at the overall direction of travel.The mean number of non-vaccine NASs for the past five years(201721)is now 63.0,up from the 53.0 five-year figure reported

18、 last year.Not only is the rolling average creeping up,its also opening up more and more road between it and previous five-year means:41.6 for 201216,30.8 for 200711,and 26.8 for 200206.In other words,the pharma industry has managed to more than double its mean output over the past decade.In travel

19、terms,it really is going supersonic.5The 2021 NAS StatisticsUnpacking this years newcomersWith the pharma plane packed to the rafters with excited newcomers venturing out into the wider world for the first time,lets take a look at the full passenger list.After months of careful curation,we can prese

20、nt to you in Table 1(overleaf)the definitive list of 2021s new active substance launches worldwide.Included in this alphabetical list by INN or equivalent is data on the companies involved,diseases which the drugs are approved for and their mechanisms of action,where the launches first occurred,and

21、indications of novelty and rare disease/orphan drug status.Well go on to analyse our roster of travellers by each of these measures through the rest of this report.As noted already,there are only 95 rows in the table and 95 products,but because two products are combination drugs which contain two NA

22、Ss,our overall NAS count comes in at 97.6GENERIC DRUG NAMETRADE NAMECOMPANYDRUG DISEASEMECHANISM OF ACTIONDRUG COUNTRYMONTH OF LAUNCHFIRST-IN-CLASS?RARE DISEASE?ORPHAN DRUG STATUS?aducanumabAduhelmBiogen/EisaiAlzheimers diseaseBeta amyloid protein antagonistUSAJulyYNNainuovurineAi bang deKainos Medi

23、cine/Jiangsu Aidea PharmaceuticalHIV/AIDS infectionNon-nucleoside reverse transcriptase inhinitorChinaSeptemberNNNallogeneic processed thymus tissue-agdcRethymicEnzyvant Sciences/Sumitomo Danippon PharmaDiGeorge syndromeNot applicableUSANovemberNYYamivantamabRybrevantJanssen(Johnson&Johnson)Non-smal

24、l cell lung cancerEGFR antagonist/MET tyrosine kinase inhibitorUSAJuneNNNanamorelin hydrochlorideAdlumizOno PharmaceuticalAnorexia/cachexiaGrowth hormone secretagogue receptor agonistJapanMarchNNNanifrolumabSaphneloAstraZenecaSystemic lupus erythematosusInterferon(type I)receptor antagonistJapanNove

25、mberYNNasciminibScemblixNovartisChronic myelogenous leukaemiaBcr-Abl inhibitorUSAOctoberNYYatogepantQuliptaAbbVieMigraine prophylaxisCalcitonin receptor-like receptor antagonistUSAOctoberNNNavacopanTavneosChemoCentryxVasculitis/Microscopic polyangiitisC5a inhibitorUSAOctoberYYYavalglucosidase alfaNe

26、xviazymeSanofiPompes diseaseAlpha glucosidase stimulantUSAAugustNYYbelumosudilRezurockKadman HoldingsGraft-versus-host diseaseRho-associated kinase 2 inhibitorUSAAugustNYYbelzutifanWeliregMerck&CoRenal and pancreat-ic neuroendocrine cancers and Hae-mangioblastioma in Von Hippel-Lindau diseaseHypoxia

27、-inducible factor 2 alpha antagonistUSASeptemberYYYbencycloquidium bromideBiLiTingYingu PharmaceuticalAllegric rhinitisMuscarinic M3/M1 antagonistChinaSeptemberNNNbimekizumabBimzelxUCBPlaque psoriasisInterleukin 17A/17F antagonistGermanySeptemberYNNcasimersenAmondys 45Sarepta TherapeuticsDuchennes m

28、uscular dystrophyDystrophin stimulantUSAJuneNYYcetuximab sarotalocanAkaluxRakuten MedicalHead and neck cancerEGFR antagonistJapanFebruaryNNNcilgavimab+tixagevimab*EvusheldAstraZenecaCOVID-19 infection prophylaxisSurface glycoprotein(SARS-CoV-2)antagonistFrance,Singapore,USADecemberNNNciprofolCyclapo

29、folHaisco PharmaceuticalAnaesthesiaGABA A receptor agonistChinaNovemberNNNclascoteroneWinleviCassiopea/Sun Pharmaceutical IndustriesAcneAndrogen receptor antagonistUSANovemberNNNcontezolidYouXiTaiMicuRxSkin and soft tissue infectionsProtein 50S ribosomal subunit inhibitorChinaNovemberNNNCOVID-19 vac

30、cine,Anhui Zhifei Longcom BiopharmaZifivaxAnhui Zhifel Longcom Biopharma/Changqing Zhifei BiologicalCOVID-19 prophylaxisImmunostimulantUzbekistanAprilNNNTABLE 1:New active substance launches,20217COVID-19 vaccine,AstraZenecaCovishieldAstraZeneca/Oxford BiomedicaCOVID-19 prophylaxisImmunostimulantUKJ

31、anuaryNNNCOVID-19 vaccine,Bharat Biotech-1CovaxinBharat BiotechCOVID-19 prophylaxisImmunostimulantIndiaMarchNNNCOVID-19 vaccine,CanSino BiologicsConvideciaCanSino BiologicsCOVID-19 prophylaxisImmunostimulantPakistanMarchNNNCOVID-19 vaccine,CIGB-2AbdalaCIGBCOVID-19 prophylaxisImmunostimulantVietnamSe

32、ptemberNNNCOVID-19 vaccine,Finlay Institute-2Soberana 2Finlay InstituteCOVID-19 prophylaxisImmunostimulantVenezuelaNovemberNNNCOVID-19 vaccine,Johnson&JohnsonJanssen COVID-19 VaccineJohnson&JohnsonCOVID-19 prophylaxisImmunostimulantSouth AfricaFebruaryNNNCOVID-19 vaccine,Medigen Vaccines Biologics C

33、o.MVC COVID-19 VaccineDynavax Technologies/Medigen BiotechnologyCOVID-19 prophylaxisImmunostimulantTaiwanAugustNNNCOVID-19 vaccine,Shifa PharmedCOVIran BarakatShifa PharmedCOVID-19 prophylaxisImmunostimulantIranJuneNNNCOVID-19 vaccine,SinopharmSinovacWuhan Inst of Biological Sciences/Sinopharm/China

34、l National Biotec GroupCOVID-19 prophylaxis and treatmentImmunostimulantChinaJulyNNNCOVID-19 vaccine,VaxineSpikoGenVaxine/CinnaGenCOVID-19 prophylaxis and treatmentImmunostimulantIranNovemberNNNcridanimodNeovirPharmasynthezHBV,HIV and HPV infectionProgesterone receptor agonist;Interferon receptor ag

35、onistRussiaAprilNNNdisitamab vedoti-naideAidexiRemeGen/Rongchang Pharmaceu-ticalsGastrointestinal stomach cancerTubulin inhibitorChinaJulyNYYdocaravimab+miro-mavimab*TwinrabZydus CadilaInfection,rabies prophylaxisImmunostimulantIndiaMarchNNNdostarlimabJemperliGlaxoSmith-KlineEndometrial cancerPD-1 a

36、ntagonistUSAMayNNNenvafolimabEnweida3D MedicinesColorectal and gastronistelinal stomach cancerPD-L1 antagonist/Immune checkpoint inhibitorChinaDecemberNYNetesevimabEli LillyCOVID-19 treatment and prophylaxisSurface glycoprotein(SARS-CoV-2)antagonistItalyJuneNNNevinacumabEvkeezaRegeneronHomozygous fa

37、milial hypercho-lesterolaemiaAngiopoietin-like 3 inhibitorUSAFebruaryYYYfinerenoneKerendiaBayerDiabetic nephropathyAldosterone antagonistUSAJulyNNNfosdenopterinNulibryBridgeBio PharmaMolybdenum cofactor deficiency Molybdenum cofactor stimulantUSAMayYYYfurmonertinibIvesaAllist Pharma-ceuticalsNon-sma

38、ll cell lung cancerEGFR kinase inhibitorChinaMarchNNNfuzuloparibAiruiyiJiangsu Hengrui Pharmaceu-ticalsEpithelial ovarian,fallopian tube and primary peritoneal cancer Poly ADP ribose polymerase 1/2 inhibitorChinaJanuaryNYNhetrombopag olamineHengQuJiangsu Hengrui Pharmaceu-ticalsPrimary immune thromb

39、ocytopeniaThrombopoietin agonistChinaSeptemberNYNGENERIC DRUG NAMETRADE NAMECOMPANYDRUG DISEASEMECHANISM OF ACTIONDRUG COUNTRYMONTH OF LAUNCHFIRST-IN-CLASS?RARE DISEASE?ORPHAN DRUG STATUS?TABLE 1:New active substance launches,2021(Contd)8ibrexafungerpBrexafemmeScynexisVulvovaginal candidiasis1,3-Bet

40、a-glucan synthase inhibitorUSASeptemberNNYidecabtagene vicleucelAbecmaBristol-Myers SquibbMultiple myelomaT cell stimulantUSAMayNYYimegliminTwymeegSumitomo Dain-ppon Pharma/PoxelType 2 diabetesGluconeogenesis inhibitorJapanSeptemberNNNimlifidaseIdefirixHansa BiopharmaKidney transplant rejectionEndop

41、eptidase stimulantFinland,the Netherlands,SwedenSeptemberYNYinclisiranLeqvioNovartisHeterozygous familial hypercho-lesterolaemiaPCSK9 inhibitorThe EUNovemberNYNinfigratinibTruseltiqBridgeBio PharmaBiliary cancerFGF receptor 1/2/3 tyrosine kinase inhibitorUSAJuneNYYinolimomabLeukotacMediolanum Farmac

42、euticiGraft-versus-host diseaseInterleukin 2 receptor antagonistFranceJanuaryNYYlazertinibLeclazaGenosoco/YuHanNon-small cell lung cancerEGFR kinase inhibitorSouth KoreaAuguatNNNlisocabtagene ma-raleucelBreyanziBristol-Myers SquibbDiffuse large B-cell lymphoma/follicular lymphomaT cell stimulantUSAM

43、ayNYYlonafarnibZokinvyEiger BioPhar-maceuticalsProgeriaFarnesyltransferase inhibitor/P glycoprotein inhibitor/MRP inhibitorUSAJanuaryYYYloncastuximab tesirineZynlontaAuven TherapeuticsDiffuse large B-cell lymphomaDNA inhibitorUSAMayNYYmaralixibatLivmarliMirum Phar-maceuticals/LumenaAlagille syndrome

44、Ileal bile acid transporter inhibitor/Sodium/bile acid co-transporter inhibitorUSANovemberNYNmargetuximabMargenzaMacroGenicsBreast cancerErbB-2 antagonistUSAMarchNNNmaribavirLivtencityTakeda/Glax-oSmithKlineCytomegalovirus infectionCytomegalovirus UL97 protein kinase inhibitorUSADecemberYYYmobocerti

45、nibExkivityTakedaNon-small cell lung cancerTyrosine kinase inhibitor/ErbB-2 antagonist/EGFR antagonistUSASeptemberNNYmolidustatMusredoBayerRenal disease-induced anaemiaHIF prolyl hydroxylase inhibitorJapanAprilNNNmolnupiravirLagevrioMerck&Co/Ridgeback TherapeuticsCOVID-19 infectionViral replication

46、inhibitorUSADecemberNNNnaxitamabDanyelzaY-mAbs TherapeuticsNeuroblastomaGanglioside antigen GD2 antagonistUSAMarchNYYnirmatrelvirPaxlovidPfizerCOVID-19 infectionSARS 3 cysteine-like protease inhibitorUSADecemberYNNodevixibatBylvayAlbireo PharmaProgressive familial intrahepatic cholestasisIleal bile

47、acid transport inhibitorUSAAugustNYYolanzapine+sami-dorphan*LybalviAlkermesBipolar disorder/SchizophreniaOpioid delta/kappa/mu receptor agonist/Opioid delta/kappa receptor antagonist/5 Hydroxytryptamine 2A/2C/6 receptor antago-nist/Dopamine D1/D2/D3/D4 receptor antagonistUSAOctoberNNNoliceridineOlin

48、vykTrevenaPost-operative painOpioid mu receptor agonistUSAJanuaryNNNGENERIC DRUG NAMETRADE NAMECOMPANYDRUG DISEASEMECHANISM OF ACTIONDRUG COUNTRYMONTH OF LAUNCHFIRST-IN-CLASS?RARE DISEASE?ORPHAN DRUG STATUS?TABLE 1:New active substance launches,2021(Contd)9olverembatinibNerikeAscentage Phar-ma/Guang

49、zhou Pharmaceuti-cals/Innovent BiologicsChronic myelogenous leukemiaBcr-Abl inhibitor/C-kit inhibitorChinaDecemberNYNorelabrutinibYinuokaiAscentage Phar-ma/Guangzhou Pharmaceuti-cals/Innovent BiologicsChronic lymphocyt-ic leukaemia/Man-tle cell lymphomaBruton tyrosine kinase inhibitorChinaJanuaryNYN

50、pabinafusp alfaIzcargoJCR Pharmaceu-ticalsMucopolysacchari-dosis IIIduronate 2 sulfatase stimulantJapanMayNYYpamiparibPartruvixBeiGeneOvaran cancerPoly ADP ribose polymerase 1/2 inhibitorChinaMayNYNpegcetacoplanEmpaveliApellisParoxysmal nocturnal haemoglobinuriaComplement C3 convertase inhibitorUSAJ

51、ulyYYYpenpulimabAnnikolAkeso BiopharmaHodgkins lymphomaPD-1 antagonistChinaAugustNYNpneumococcal vac-cine,20-valent,PfizerPrevnar20PfizerPneumococcal infection prophylaxisImmunostimulantUSAJulyNNNponesimodPonvoryJohnson&JohnsonRelapsing-remitting multiple sclerosisSphingosine 1-phosphate 1 receptor

52、agonistEU/USAJulyNNNregdanvimabRegkironaCelltrionCOVID-19 prophylaxis and treatmentSurface glycoprotein(SARS-CoV-2)antagonistSouth KoreaNovemberNNNrelmacabtagene autoleucelRelma-celJW TherapeuticsDiffuse large B-cell lymphomaT cell stimulantChinaNovemberNYNsavolitinibOrpathysHutchmed/AstraZenecaNon-

53、small cell lung cancerMET tyrosine kinase inhibitorChinaJulyNNNsetmelanotideImcivreeRhythm Phar-maceuticalsPOMC deficiency/Leptin receptor deficiency obesityMelanocortin MC-4 receptor agonist/Melanocyte stimulating hormone receptor agonistUSASeptemberNYYsomapacitanSogroyaNovo NordiskGrowth hormone d

54、eficiencyGrowth hormone receptor agonistUSAOctoberNNNsotagliflozinZynquistaLexicon Phar-maceuticalsType 1 diabetesSodium/glucose cotransporter 2/1 inhibitorEU/USADecemberYNNsotorasibLumakrasAmgenNon-small cell lung cancerK-Ras inhibitorUSAAugustYNYsotrovimabXevudyGlaxoSmith-KlineCOVID-19 infectionSu

55、rface glycoprotein(SARS-CoV-2)antagonistAustraliaOctoberNNNsurufatinibSulandaHutchmedNeuroendocrine cancerVEGFR-1/2/3 tyrosine kinase inhibitor/FGF receptor 1 tyrosine kinase inhibitor/Colony stimulating factor 1 receptor antagonistChinaJanuaryNNYtelitaciceptTaiAiRemeGen/Rongchang Pharmaceu-ticalsSy

56、stemic lupus erythrematosus B-cell activating factor inhibitor/APRIL inhibitorChinaAugustYNNteserpaturevDelytactDaiichi SankyoBrain cancer/GliomaImmuno-oncology therapyJapanNovemberNYYtirbanibulinKlisyrAlmirallActinic keratosisSrc inhibitor/Tubulin polymerization inhibitorUSAFebruaryNNNtisotumab ved

57、otinTivdakGenmab/SeagenCervical cancerTubulin inhibitorUSASeptemberNNNtralokinumabAdbryLeo PharmaAtopic eczemaInterleukin 13 antagonistUSADecemberYNNtrilaciclibCoselaBoehringer Ingelheim/G1 TherapeuticsNon-small cell lung cancerCyclin-dependent kinase 4/6 inhibitorUSAMarchNYNGENERIC DRUG NAMETRADE N

58、AMECOMPANYDRUG DISEASEMECHANISM OF ACTIONDRUG COUNTRYMONTH OF LAUNCHFIRST-IN-CLASS?RARE DISEASE?ORPHAN DRUG STATUS?TABLE 1:New active substance launches,2021(Contd)10umbralisibUkoniqRhizen Phar-maceuticals/TG TherapeuticsB-cell/follicular lymphomaPI3 kinase delta inhibitor/Casein kinase 1 inhibitorU

59、SAAugustYYYupacicalcet sodium hydrateUpasitaEA Pharma/Eisai/Sanwa Kagaku Kenky-ushoSecondary hyper-parathyroidismCalcium-sensing receptor agonistJapanSeptemberNYNvaricella zoster vac-cine,Green CrossSuduvax-IIGC PharmaVaricella zoster infection prophylaxisImmunostimulantSouth KoreaSeptemberNNNverici

60、guatVerquvoBayer/Merck&CoChronic heart failureGuanylate cyclase stimulantJapanSeptemberNNNvoclosporinLupkynisAurina Pharma-ceuticalsLupus nephritisCalcineurin inhibitorUSAJanuaryNYNvosoritideVoxzogoBioMarinAchondroplasiaNatriuretic peptide agonistFrance/GermanySeptemberNYYzimberelimabYuTuoHarbin Glo

61、ria Pharmaceu-ticalsHodgkins lym-phomaPD-1 antagonistChinaSeptemberNYNGENERIC DRUG NAMETRADE NAMECOMPANYDRUG DISEASEMECHANISM OF ACTIONDRUG COUNTRYMONTH OF LAUNCHFIRST-IN-CLASS?RARE DISEASE?ORPHAN DRUG STATUS?Source:Pharmaprojects,February 2022*Both components are NASs*Just this component is a NAS N

62、ovel mechanism of actionTABLE 1:New active substance launches,2021(Contd)11Theres a lot to digest in that jumbo-sized list of new drugs,so lets start to break those new drugs down by a number of different parameters.Table 2 lists all of the companies which launched more than one NAS during the year,

63、and where they fell in our chart of companies by pipeline size,on the basis that the best performance could be considered the most drugs delivered from the smallest pipeline.It also includes for reference the performance of any top 10 pharmas which didnt manage to bring to the market two or more dru

64、gs.Spearheading the charge into new territory last year was UK-headquartered AstraZeneca,the only company to successfully introduce five new active substances.As well as its renowned COVID-19 vaccine,and its combination anti-COVID antibody product Evusheld(both of which,more later),it delivered a no

65、vel NAS for lupus in the shape of Saphnelo(anifrolumab)and,in China,launched a new MET tyrosine kinase inhibitor for use against non-small cell lung cancer,Orpathys(savolitinib).This was more than double what it delivered in 2020,when Gilead and Pfizer tied for pole position with four NASs apiece.Pf

66、izer was back on the leaderboard with two 2021 NASs,but it looks like Gilead ran out of gas.Four companies launched a trio of salvos into NAS land,with Bayer having the best NAS launch to pipeline size ratio,being only fourteenth in terms of size of its overall R&D portfolio.It was joined here by Jo

67、hnson&Johnson,Merck&Co,and GlaxoSmithKline,the latter of which also launched three drugs in 2020,and thus could be said to be the most consistent performer during the pandemic years.There follows a dozen companies with TABLE 2:Top company NAS launch performance,2021COMPANY NO.OF NAS LAUNCHES 2021POS

68、ITION BY PIPELINE SIZEAstraZeneca56Bayer314GlaxoSmithKline311Johnson&Johnson38Merck&Co37Guangzhou Pharmaceuticals24,149RemeGen/Rongchang Pharmaceuticals2457Ascentage2336BridgeBio Pharma2100Hutchmed2212Innovent Biologics254Sumitomo Dainippon225Eisai218Jiangsu Hengrui Pharmaceuticals216Pfizer25Bristol

69、 Myers Squibb24Takeda23Novartis21Eli Lilly110Sanofi19Roche02Source:Pharmaprojects,February 202212a pair of agents in the arrivals lounge.These include five companies outside of the top 25 by pipeline size,four of which are Chinese,with Guangzhou Pharmaceuticals being the company with the biggest NAS

70、 launch to pipeline size ratio.They are joined by BridgeBio Pharma in the US,which launched two drugs for rare diseases there:Nulibry(fosdenopterin)and Truseltiq(infigratinib)for molybdenum cofactor deficiency and biliary cancer,respectively.A further seven of the dual drug deliverers are top 25 com

71、panies,including one of the first Chinese-headquartered firms to enter the upper echelons of our chart,Jiangsu Hengrui Pharmaceuticals.Like last year,only three top 10 pharmas missed out on providing more than one new drug,with Roche finding itself unable to get anything over the line during calenda

72、r 2021.But it did launch three new drugs in 2020.Overall,the biggest 10 pharma companies,which are now just developing 4.6%of all drugs,were involved in launching 18 of the 97 NASs,or 18.6%,suggesting that the might of Big Pharma still has the muscle to get its drugs all the way to the finish line.B

73、ut this is only part of the story.Revisit Table 1 and look at how many companies last year delivered NASs without any involvement from a sizeable partner.There are plenty of names there which you might not even have heard of,never mind them not being household names.In many ways,2021 was a year when

74、 the pharma minnows came good.Moving on to carve up the NAS continent into its various different therapeutic area habitats,cancer has reasserted itself at the summit,with the largest number of novel introductions:30.This is quite an uptick from the 22 launched during 2020,and,given the pre-eminent s

75、tate of cancer drugs in the overall pipeline,sees order being restored after it was temporarily overthrown last time.But the COVID bounce for anti-infectives is clearly far from over.It comes in second with 27 NASs,but even though it was forced into second place,it is still an enhanced total,compara

76、ble to the 28 it launched in 2020,and way beyond recent historic levels(2019s number was just 5).Between them,these two therapeutic areas accounted for 59%of all new active substances,even more than the 58%reported twelve months prior.Elsewhere,the alimentary/metabolic group hit double-digits,easily

77、 surpassing the three delivered in 2020,to become 2021s third most successful therapeutic area.It pushed neurologicals down to fourth with 7,followed by immunological agents with 6.There were slim pickings for the remainder of the therapeutic groups.132021 was a particularly successful year for biot

78、echnology-based drugs,with 44(45%)of the NASs falling into this class.This far surpassed the 33%seen last year,and is also just a little higher than the proportion of drugs in the overall pipeline of this type.Nineteen of these were monoclonal antibodies(spread across 17 products,as two are dual MAb

79、 combos),plus an additional two bispecific antibodies.There were eight recombinant vaccines,four gene therapies,four antibody-drug conjugates,three chimeric antigen receptor T-cell(CAR-T)therapeutics,and three fusion proteins.It was a relatively quiet year for RNA-based therapeutics,with just a sing

80、le antisense therapy(BioMarin and Sarepta Therapeutics muscular dystrophy drug Amondys 45 casimersen)and a sole RNA interference agent(Alnylam and Novartiss Leqvio inclisiran).FIGURE 2:2021 NAS launches by therapeutic group30%4%2%27%7%1%11%6%2%4%3%2Alimentary/MetabolicAnti-infectiveAnticancerBlood&C

81、lottingCardiovascularDermatologicalHormonalImmunologicalMusculoskeletalNeurologicalRespiratory Source:Pharmaprojects,February 202214In a survey from 2016 on the leading reasons why people chose a particular location for their vacation,the top answer was to experience the culture.Next came financial

82、considerations(the accommodation had a good price;the flight had a good price).Bottom of the list was it was off the beaten track.For pharma,the choice of first country to launch a NAS is seemingly a mixture of cultural and financial grounds:where the company is based and the size of the market.None

83、theless,as Figure 3 shows,some drugs still made their debuts in some of the more off-the-grid markets note that some drugs have more than one country/market as their first.307111USAChinaJapanEUFranceSouth KoreaGermanyIndiaIranAustraliaFinlandNetherlandsSwedenSingaporeItalyPakistanRussiaSouth AfricaT

84、aiwanUKUzbekistanVenezuelaVietnam45%19%9%3%3%3%3%2%2%1%1%FIGURE 3:2021 NAS launches by country/regionNot surprisingly,the US retains its stranglehold on this metric,with 46%of the NAS launches occurring there first.However,this is an erosion of its 2020 figure of 54%.But really,the developing story

85、of new active substance launches belongs to China.In 2020,it was the debut market for just seven of the 82 drugs;last year,this was up to 19,or around one fifth.With the exception of AstraZenecas Orpathys,all of these were locally originated drugs,developed by Chinese companies.Like elsewhere,cancer

86、 has become Chinas main focus,with 12 of the Chinese NASs having an oncological focus.China zoomed past Japan in terms of being the pre-eminent Asian country for first launches,Source:Pharmaprojects,February 202215with the latter booking just nine last year.Europe is languishing well behind China no

87、w,with just 11 of the NASs being first rolled-out there.The righthand-most columns of Table 1 give an indication of whether our NASs were launched for rare diseases,and whether these developments were encouraged by concomitant orphan drug designations.A rare disease is defined as one with a prevalen

88、ce lower than one in every 2,000 people in the EU,or affecting fewer than 200,000 people in the US(equivalent to around one in every 1,600 people).Last year,39 of the 97 NASs were developed for rare diseases,which represented both an increase in the overall number from 2020,which reported 28,and a r

89、ise in the percentage(40.2%vs 34.1%).However,the percentage which had orphan drug status granted for the disease they got approved for fell back,to just 30.9%.Why is that?It could simply be a function of the increased number of NASs which debuted in countries which dont have an orphan drug status sc

90、heme,such as China.As Table 1 showed,generally,in the West,rare diseases and ODS still go mostly hand-in-hand.So,our guidebook of the demographics and culture draws to a close,and its time to delve into the unique must-see places of interest in our 2021 NAS country tour.27.527.136.152.23735.236.840.

91、835.630.901020304050602012201320142015201620172018201920202021%OF NASS WITH ODSYEARFIGURE 4:Percentage of NAS launches with an orphan drug designation,201221 Source:Pharmaprojects,February 2022NOTE:201621 figures refer only to drugs with orphan drug status for their marketed indication in their mark

92、eted country.16The Novel NASs of 2021:New vistas open up in cancer and inflammation,as pharma plants its flag across multiple new territoriesTravel,like pharma R&D,begins with discovering something new.Even in our interconnected 21st century world,there are still parts of our planet which are,to all

93、 extents and purposes,unexplored and unknown to most of the human race.These range from mountains in Bhutan which have never been climbed,down to what paradoxically is the biggest mountain range on the planet,the mid-ocean ridge,the extent of which has only recently been fully mapped,due to the fact

94、 that it is entirely at the bottom of the ocean.Then there is the southern Namib desert in Namibia,thought to be largely unexplored,mainly because of the fact that there isnt really much there to explore anyway.At the other end of the scale,there are areas of dense jungle in the Amazon rainforest wh

95、ich remain unmapped and still throw up unknown tribes of indigenous people,seemingly completely cut off from the outside world.Then there are numerous tiny islands sprinkled around the globe about which little is known,such as the enigmatic North Sentinel Island a tiny dot on the map,ostensibly owne

96、d by India,but actually protected by a three-mile exclusion zone as the native islanders remain hostile to outsiders.Despite these pockets of wonder yet to be delved into,our world is now pretty well charted,with the Google Earth project taking things to the next level this century.In comparison,our

97、 understanding of diseases and the development of drugs to treat them is probably only in the Middle Ages,with the completion of the Human Genome Project and the associated biotech revolution probably being akin to the discovery of the New World.In other words,weve made some great leaps forward,but

98、there are still entire continents of pathology of which we only have the scantest maps as yet.There is much to explore,much to learn,much to discover.The good news is that,every year,the pharmaceutical industry brings to market a set of drugs which open up brand new vistas of never-before-seen ways

99、to treat diseases,by bringing not just new drugs,but new kinds of drugs,to the market the novel NASs.Our strict definition of novelty here is that a drug is novel if its the first to reach the market with a particular mechanism of action,and thats what well focus on here in this section of the repor

100、t.Of course,there are other forms of innovation,and other reasons why drugs might be considered significant,and well come to those later.During 2021,using this definition,17 were first-in-class.Thats actually exactly the same number we saw in 2020,but given the overall NAS total is higher,it means t

101、hat the percentage of 2021 NASs classed as novel has fallen:from 21.5%down to 17.5%.It would though be churlish to suggest that 2021 the year which saw the pharma industry become the conquistadors of COVID was not a big year for innovation.Its been an anomalous period of time in so many ways,with th

102、e virus diverting the gaze of many.Lets instead here celebrate the new territories which pharma conquered,despite everything thrown in its path.Weve already seen how cancer is leading the way in the total number of R&D drugs,share of pipeline,and,in this report,new active substances launches.And its

103、 also near the front of the queue for speedy boarding onto the plane in terms of delivering novelty,with three NASs classed as novel by our definition.This is a slight improvement on 2020,which,despite the enormous oncology pipeline,only saw two innovative anticancers cross the finish line.Even so,i

104、t might to some feel like arriving at a hotel which doesnt live up to the brochure pictures.We saw in the main Pharma R&D Report that one of the drug mechanisms of action which experienced the biggest increase in popularity was K-Ras inhibition,and 2021 saw the first drug of this type reach the mark

105、et.This was 17Amgens Lumakras(sotorasib),which gained the green light for non-small cell lung cancer in the US initially,followed by a slew of subsequent approvals elsewhere.As such,it beat no fewer than 77 drugs in active development to the finish line,in the most crowded field for any of last year

106、s new mechanisms.Closest behind in the rear-view mirror is Mirati Therapeutics adagrasib,which is currently awaiting approval,also for NSCLC in the US.Meanwhile,Amgen is looking to expand its agent into a number of other tumour types,with colorectal being the most advanced,in Phase III.Merck&Co was

107、also on the tour bus with its Welireg(belzutifan),the worlds first hypoxia-inducible factor 2 alpha antagonist.HIF-2 is involved in von Hippel-Lindau disease,a syndrome characterised by visceral cysts and benign tumours which often undergo subsequent malignant transformation.The full indication for

108、which this new drug has been approved is for use in patients with von Hippel-Lindau disease who require therapy for associated renal cell carcinoma,central nervous system haemangioblastomas,or pancreatic neuroendocrine tumours.Unsurprisingly,the drug received orphan drug status in the US for this ni

109、che condition,and has received the same leg-up in Australia.The drug came into Mercks orbit following its 2019 acquisition of Peloton Therapeutics.The final anticancer novel NAS for 2021 was developed away from Big Pharma,under a collaboration between Rhizen Pharmaceuticals and TG Therapeutics.Their

110、 Ukoniq(umbralisib)is a PI3 kinase delta inhibitor with the additional,novel pharmacology of casein kinase 1 inhibition.Completing a clean sweep for novel oncological introductions in the US,this drug is available for use in adult patients with relapsed or refractory marginal zone lymphoma after at

111、least one prior anti-CD20 based regimen and adult patients with relapsed or refractory follicular lymphoma after at least three prior lines of systemic therapy.The review process here was expedited by both priority review and breakthrough designation in the US,and follow-on indications include chron

112、ic lymphocytic lymphoma(for which it has been filed)and diffuse large B-cell lymphoma.It was an unusually good year for the autoimmune and inflammation area,which under its broadest definition actually delivered the most innovation,with six drugs with previously undeveloped mechanisms reaching their

113、 destinations.Two of these were for systemic lupus erythematosus.AstraZenecas Saphnelo became the first interferon(type I)receptor antagonist when it was launched in Japan in November.Earlier in the year,and completing the pair of the only two drugs to launch first in countries outside the US and EU

114、,was the first APRIL inhibitor,Taiai(telitacicept).This is notable as its a still(as yet)rare example of a completely novel mechanism to come out of China.It was developed there by RemeGen,part of Rongchang Pharmaceuticals,and is a fusion protein which jointly targets BLyS and the aforementioned nov

115、el target APRIL.APRIL,or CD256,is a proliferation-inducing ligand which is important in B-cell development.Its another landmark on Chinas long march from being just a generics-developing country,via me-too drugs,to producing new agents of genuine novelty.The complement system is a complex cascade in

116、volved in clotting as well as inflammatory processes,and is the target for two more of our 2021 novel NASs,one of which falls in the latter bucket.Tavneos/Vynpenta(avacopan)has been developed by ChemoCentryx for use in severe active anti-neutrophil cytoplasmic autoantibody-associated vasculitis,spec

117、ifically granulomatosis with polyangiitis and microscopic polyangiitis syndromes whereby blood vessels are destroyed by inflammation.The drug,a small molecule,is the first to target complement C5a receptor 1.Potential follow-on indications include haemolytic uraemic syndrome,G3 glomerulopathy,and hi

118、dradenitis suppurativa.18Kidney transplant rejection is the focus of our only enzyme-based novel NAS of the year.Hansa Biopharmas Idefirix(imlifidase)has been launched in the US;its the first drug classified as an endopeptidase stimulant,and is actually a proteolytic enzyme derived from the bacteriu

119、m Streptococcus pyogenes.It has a high affinity for IgG antibodies,hence its use in the treatment of organ transplant rejection.It also has potential use in Guillain-Barr syndrome.In the dermatological inflammation arena,we have two new novel agents,both based around interleukin antagonism.Adbry(tra

120、lokinumab)is a new monoclonal from Leo Pharma for the treatment of atopic eczema,which just squeaked its launch in at the end of the year.It is the first interleukin-13 antagonist to successfully complete its voyage to the market,docking ahead of similar monoclonals from AbbVie/Bristol Myers Squibb

121、and Almirall/Eli Lilly in the shapes of cendakimab and lebrikizumab,respectively,both of which are still far out to sea in Phase III trials.We also saw the introduction of UCBs Bimzelx(bimekizumab),which is a dual interleukin-17A and-17F antagonist,and its the latter of these two pharmacologies whic

122、h hasnt been seen in a launched drug before.This agent debuted in Germany in September for use in moderate-to-severe plaque psoriasis,and other launches in Sweden,the UK and then the Netherlands swiftly followed.Judging by the number of times the drug is mentioned in UCBs annual report,the company c

123、learly feels that,with prevailing winds,this product could become head of its fleet.The travel industry has undoubtedly suffered heavily during the past two pandemic years.Overseas trips were,from many countries,completely forbidden at many points.Almost as bad,in the UK at least,we faced periods wh

124、ere the rules would change at very short notice.I myself experienced this when trying to go on holiday in September 2020.With international travel from Great Britain having restarted,and having booked a vacation to Ibiza in Spain,two weeks before departure,Spain went on the UKs red list,making a hol

125、iday there untenable.I quickly cancelled everything and rebooked a trip to Croatia only to find that country fall to the red list a week later,at which point,I gave up and decided to holiday in Yorkshire instead!This on-again,off-again uncertainty would sound familiar to the developers of the years

126、most controversial drug launch,Aduhelm(aducanumab).This novel NAS is the first beta-amyloid protein antagonist to reach the market,but neither its journey to get there,nor its fate after its arrival,have exactly followed straightforward trajectories.Many drugs attempting to use the beta-amyloid hypo

127、thesis to voyage to find the Golden Fleece of a treatment for Alzheimers disease found themselves shipwrecked and all at sea at Phase III development.Notable casualties finding their hopes dashed on the rocks in recent years included Pfizer and Johnson&Johnsons bapineuzumab,and Eli Lillys solanezuma

128、b.Aduhelms developers,Biogen and Eisai,have found themselves manning the lifeboats too previously:this drug began Phase III trials as far back as 2015,and the first two trials ran aground in 2019 after a negative futility analysis.But after a spell on a desert island,the companies built a raft for t

129、he monoclonal antibody and refloated its Phase III effort,crunching the data differently to show a much-debated efficacy signal in one of the trials.Emboldened,the companies filed an NDA,but the FDAs Advisory Committee wasnt impressed and decided that the cognitive benefit wasnt yet proven,voting 10

130、 to 1 against approval.It was to many observers surprise,then,when the FDA gave the drug the thumbs up in June,on the basis of the positive biomarker data alone.But it has been far from plain sailing since.Three Advisory Committee members resigned over the decision,amid a general outcry from many in

131、 the industry and beyond.Nonetheless,Biogen launched the drug in the US in July,promising to complete a confirmatory trial.19However,payers in the US,such as Medicare,have decided that they wont pay for the drug,leaving it in the twilight zone of being approved but largely unavailable,as few are con

132、vinced that it actually works.Thus,sales have barely made it out of port.Despite many continuing to doubt the entire validity of the amyloid hypothesis in Alzheimers,one side effect of this salty saga has been that it has given the kiss of life to several previously beached beta-amyloid protein anta

133、gonists,notably the aforementioned solanezumab.On a different shore,anti-infectives last year yielded just two novel NASs,one of which,unsurprisingly came along with COVID:Pfizers much-lauded Paxlovid(nirmatrelvir,administered with ritonavir to extend its half-life).This may have been the second dir

134、ect anti-SARS-CoV-2 antiviral to make it to market,but clinical trial results demonstrated it to be more effective than Merck&Co/Ridgebacks Lagevrio(molnupiravir),it being found to reduce the risk of hospitalisation or death by 89%,compared to 50%for the latter.It also qualifies as novel,being the f

135、irst SARS 3 cysteine-like protease inhibitor to be launched,with the field for Pfizer looking pretty clear(only Shionogis Phase III candidate S-217622 is currently beyond the preclinical phase).The Merck drugs mechanism is less clear cut:its reported to cause mutations in RNA synthesis by acting as

136、a dummy amino acid,so we have it classified as a general viral replication inhibitor for now,thus rendering it non-novel.Despite the COVID hegemony,other viruses are available.Takeda and GlaxoSmithKline teamed up to deliver Livtencity(maribavir),the worlds first cytomegalovirus UL97 protein kinase i

137、nhibitor,to tackle cytomegalovirus infection.CMV is already endemic,but can be problematic in those with immunosuppressive disorders.It was a serious problem during the height of the AIDS crisis,when it caused a lot of patients to lose their sight via CMV retinitis.Although this threat has largely p

138、assed,its good to have an additional selection available in the therapeutic minibar.The fact that serious CMV infections are relatively rare now is also a reminder of how viral threats can ebb and flow with some rapidity.Talking of rare,if you want something really niche,you might want to embark on

139、a trip to see the sights of BridgeBio Pharmas second product to market,as we move to look at novel new active substances for metabolic diseases.Nulibry is a molybdenum cofactor replacement therapy for molybdenum cofactor deficiency.This is an ultrarare genetic disorder caused by a mutation in the MO

140、CS1 gene,which usually leads to death within months of birth.As is often the case with drugs developed for diseases which only affect a very small number of patients,the life-saving treatment comes with an eye-watering price tag$500,000 per year in this case.With only around 150 patients to treat wo

141、rldwide however,such a high cost was to be expected if Bridge is to recoup its development costs.Another somewhat obscure backwater is progeria.Also known as Hutchinson-Gilford syndrome,progeria,as the name suggests,is a condition whereby patients appear to undergo accelerated aging,leading to death

142、 in the second decade of life.Its extremely rare,being thought to affect one in 18 million people.Riding to the rescue here is Eiger BioPharmaceuticals,which licensed in Zokinvy(lonafarnib)from Merck&Co.The drug has multiple actions,two of which are novel in a launched drug:P-glycoprotein inhibition

143、 and MRP inhibition.Interestingly,this agent also has activity against an infectious pathogen,the hepatitis D virus.Zokinvys price makes Nulibry look like a bargain basement cheap awayday;coming in at surplus to$1m per year,its now the most expensive drug on the books in the US.Somewhat more prosaic

144、 is our third novel NAS under the metabolic sunshade,Lexicon Pharmaceuticals Zynquista(sotagliflozin),which 20is for the far more prevalent condition of type 1 diabetes.While over 20 inhibitors of sodium/glucose cotransporter 2 are already on the market,this is the first drug which combines this mec

145、hanism additionally with sodium/glucose cotransporter 1 inhibition.It is also awaiting approval for use in type 2 diabetes and heart failure.Bridging the lands of metabolic and haematological drug development,Apellis has developed Empaveli(pegcetacoplan),which returns us to the complement cascade th

146、eme park mentioned earlier.Its the first complement C3 convertase inhibitor,and was launched in the US last year for paroxysmal nocturnal haemoglobinuria,another rare disease,but this time one which is acquired rather than inherited.Here,the complement system destroys red blood cells,producing a hae

147、molytic anaemia.Apelliss agent is a pegylated synthetic peptide,which is also being developed for the ophthalmological condition of geographic atrophy.Lastly,we have an innovation in the big tent of cardiovascular therapeutics.Regeneron launched Evkeeza(evinacumab)for the rare lipid disorder homozyg

148、ous familial hypercholesterolaemia.While there has been considerable activity in this disease in recent years with the launch of the PCSK9 inhibitors,this drug takes a different tack,and is the debut of the strategy of angiopoietin-like 3 inhibition onto the market.The target protein inhibits the hy

149、drolysis of HDL phospholipid and thus increases the proportion of the so-called good cholesterol.This is another case of a drug being successfully developed against a condition which is not just rare,but is characterised as ultrarare,with just 1,300 patients suffering from it in the US.It means that

150、 six of the 17 novel NASs of the year were developed for use in rare diseases.In drug R&D,as in travel,a journey off the beaten track can be the most rewarding.21Other Notable NASsConquering COVIDs highest peaksIn the second of what were two extraordinary years,we have to start our review of other n

151、otable NASs which may not be classed as novel by our definition,but are nonetheless significant,with another look at COVID country.No other single disease can ever have dominated drug introductions so much in a single year,with 17 new drugs and vaccines in total(18 individual NASs,as one product is

152、a combination therapy).While no fewer than five vaccines(those from Pfizer/BioNTech,Moderna,Beijing Institute of Biological Products,Sinovac,and Russias Gamaleya Institute)made the list for 2020,and thus were launched within a year of the pandemics emergence,2021 should really be styled as the year

153、of the COVID vaccine.It was last year that the global vaccination roll-out really happened,with most of us having received three doses of the jabs during that calendar year.And COVID vaccines cant be missed in our list of NAS launches,there being 11 of them.2021 began with the launch of the Oxford U

154、niversity and AstraZeneca version,but this vaccine had a bit of a bumpy ride subsequently,perhaps unfairly.Despite the fact that AZ,unlike Pfizer and Moderna,was offering its vaccine as a non-profit option,the discovery of a very rare side-effect of blood clots tarnished its reputation somewhat,and

155、it subsequently became embroiled in post-Brexit political machinations.Elsewhere,aside from the Janssen jab,most of the other coronavirus vaccines to roll out were slightly out of the orbit of Western Big Pharma,and may not have made as much of a contribution.We already covered the second front on w

156、hich COVID is being assaulted with the small molecule antivirals,but there was also progress attacking from a third direction,with new antibody therapeutics.After 2020 had seen the introduction of Regenerons MAb combo REGEN-COV(casirivimab+imdevimab),AbCellera and Lillys bamlanivimab,and Biocads Ils

157、ira(levilimab)for COVID complications,there was further activity last year in what became a fast-moving field.There were a further four products containing five novel NAS MAbs which left the runway during 2021.AstraZeneca was in the game again,with its combination product Evusheld(cilgavimab+tixagev

158、imab)coming towards the end of the year,with subsequent data showing that it retained activity against the then newly discovered Omicron variant,which has since swept the world,visiting more countries than Michael Palin.No such luck for Eli Lilly though.Its 2020 monoclonal bamlanivimab was joined by

159、 etesevimab last year,and a combination product containing both agents was also launched.However,in January 2022,the US FDA withdrew the EUAs for both,along with those for the aforementioned REGEN-COV,as these monoclonals dont appear to be effective against Omicron.Rather than going on the trip of a

160、 lifetime,these drugs had little more than a long weekend away.There was similar bad luck for Celltrions new anti-COVID MAb Regkirona(regdanvimab),which was launched just as Omicron emerged,and is believed to be less effective against that variant too.Celltrion is punching straight back by developin

161、g a combination of its agent with a new Omicron-sensitive MAb,CT-P63.But the final MAb against the coronavirus to be launched,GlaxoSmithKlines Xevudy(sotrovimab),looks like it will fare better,reportedly having less of a drop in antiviral potency than any of the other monoclonal antibodies developed

162、 thus far.In the world of anti-COVID MAbs,things move faster than a bullet train.Away from the seemingly ubiquitous virus,there was also much to celebrate in terms of significant drug launches.Last year saw three more products added to the armoury of CAR-T therapeutics for use against cancer,effecti

163、vely doubling the size of the CAR-T war chest.Two of these came via Bristol Myers Squibb.Abecma(idecabtagene vicleucel)entered the market for the treatment of relapsed or refractory multiple 22myeloma,and encountered BMS country via its acquisition of Celgene.The companys other drug also came via BM

164、Ss shrewd M&A strategy,from its purchase of Juno Therapeutics.This was Breyanzi(lisocabtagene maraleucel),which debuted in the US for relapsed or refractory large B-cell lymphoma,including diffuse large B-cell lymphoma,high-grade B-cell lymphoma,primary mediastinal large B-cell lymphoma,and follicul

165、ar lymphoma grade 3B.Proving that the West doesnt have a monopoly on exploring this exciting new territory,the third CAR-T was from Chinas JW Therapeutics:relma-cel(relmacabtagene autoleucel),which was also launched for large B-cell lymphoma.Away from the twin peaks of COVID and cancer,there were ad

166、ditional interesting NASs for some rare metabolic syndromes,notably some biliary disorders.Both Albireo Pharmas Bylvay(odevixibat)and Mirum Pharmaceuticals Livmarli(maralixibat)are ileal bile acid transport inhibitors,with the former approved for progressive familial intrahepatic cholestasis(PFIC),a

167、nd the latter subsequently joining it on the US market for the related Alagille syndrome.Both are inherited genetic disorders.In PFIC,defects in biliary epithelial transporters cause a build-up of bile in liver cells,ultimately leading to liver failure and frequently death in childhood.In Alagille s

168、yndrome,a genetic defect causes bile duct paucity,which is characterised by narrow and malformed bile ducts.This similarly causes bile to build up in the liver,but also congenital heart problems.Mirum had originally intended to develop Livmarli for PFIC too,but,following Bylvays approval,withdrew it

169、s EU application for PFIC and went for Alagille instead.An example of where the presence of other traffic on your route can cause you to change direction and head for a new destination.Also within the city limits of rare metabolic disorders,we can visit Rhythm Pharmaceuticals Imcivree(setmelanotide)

170、,a melanocortin(MC)-4 receptor agonist and melanocyte-stimulating hormone receptor agonist.This has been approved for a number of genetic disorders which produce reduced activation of the central MC-4 receptor,leading to early-onset severe obesity and pathological hunger.Thus far,the US FDA gave the

171、 go-ahead for prescription in proopiomelanocortin,proprotein convertase subtilisin/kexin type 1 or leptin receptor deficiency confirmed by genetic testing.Further obesity-related genetic disorders are in the pipeline,with a June 2022 PDUFA date scheduled for the additional indications of Bardet-Bied

172、l syndrome and Alstrm syndrome.Rhythm took a leaf out of the oncology playbook in the development of this drug,conducting so-called basket trials,whereby it used the same investigational regimen,but divided into separate subgroups based on different markers,providing a good way to study the differen

173、t genetic variations of these inherited obesity syndromes.Lastly in metabolic land,a riddle:when is a NAS not a NAS?That may sound like a dumb question,but it was one which the EMA and the makers of Nexviazyme(avalglucosidase alfa),Sanofi,certainly struggled to agree on.The drug is a modified versio

174、n of the companys previously launched enzyme replacement therapy for Pompe disease,Myozyme(alglucosidase alfa),and the European agency believed that the newer drug could not be considered to be a new active substance because there was not enough difference between the two effectively treating it lik

175、e a prodrug(we ourselves dont count prodrugs as NASs if the active moiety has already been marketed).But Sanofi has argued that this approach is not appropriate for a biological,telling Pink Sheet“the CHMP NAS process applies a narrow interpretation of the NAS principles which is not appropriate for

176、 biological therapies and does not account for the innovative structural changes to enzyme replacement therapies,such as avalglucosidase alfa.”The distinction is important because under EU legislation,NASs are awarded a 2310-year exclusivity period(eight years of data exclusivity during which a gene

177、ric competitor cannot reference the originators data,plus an additional two-year exclusivity provision protecting against marketing of the generic).We have included the drug in our list of NASs for the year,but it does illustrate that the distinction may not always be as clear cut as you might think

178、.RNA therapeutics,while no longer exactly an undiscovered country,are still sufficiently outlying to merit a mention.As noted earlier,we have two in this batch.Leqvio,from the company with the biggest pipeline,Novartis(via its acquisition of The Medicines Company),is only the fourth RNA interference

179、 therapeutic to be successfully brought to the market.RNAi specialist Alnylam has been involved in all four,adding this drug to its portfolio comprising Onpattro(patisiran),Oxlumo(lumasiran),and Givlaari(givosiran).The new agent silences PCSK9,and is for use in the rare cardiovascular syndrome heter

180、ozygous familial hypercholesterolaemia.Similarly,Sarepta Therapeutics maintains its monopoly on antisense therapeutics using exon-skipping splice switching oligomers,with a third such launch in the form of Amondys 45,again for Duchenne muscular dystrophy.This one is for the exon 45 skipping version,

181、and,like its predecessors Exondys 51(eteplirsen)and Vyondys 53(golodirsen),won accelerated approval from the US FDA based on the belief that an increase in dystrophin production is reasonably likely to predict clinical benefit,such as improved motor function.Confirmatory clinical trials are still un

182、derway.Our final stop on our whistle-stop tour of interesting 2021 NASs by which time we will have covered almost half of the set is Verquvo(vericiguat).This Bayer and Merck&Co collaboration enters the crowded heart failure market in the US,but does have a specific,niche approved indication,namely,t

183、o reduce risk of cardiovascular death and heart failure rehospitalisation in patients with symptomatic chronic heart failure with reduced ejection fraction up to 45%,who have been hospitalised or need intravenous diuretic therapy.With that,we complete our open-top bus tour of NAS city,having seen so

184、me of the most impressive sights which are truly a monument to the pharma industrys renaissance.I think we can all agree that this has been one of our best trips yet.As ever at the end of a holiday,ones thoughts immediately turn to the next one.Where will we go next year?24In a world beset by plague

185、s and invasions,pharma continues to doggedly march to victoryOur globetrotting journey around the pharma R&D landscape and its landmark new active substances is now almost at an end.Weve seen in this report that there were more new places of interest to visit this year than ever before,as the pharma

186、 industry emerges from two of years of a disruptive pandemic,blinking into the sunshine.It seems stronger than ever,having played an enormous role in helping tame the coronavirus and returning the world to some kind of normality.Its sometimes difficult to remember that just a year ago,the vaccine ro

187、ll-out was only really beginning to pick up speed.Twelve months later and most of us have had our three doses,with some moving on to a fourth.In the UK,all coronavirus-related restrictions were removed in February and things are,essentially,back to normal.Here,92%of eligible people have received at

188、least one vaccine dose,85%two doses,and 67%a third.The speed with which the vaccines were developed,manufactured,and administered was nothing short of phenomenal.Of course there remains a significant challenge to deliver these kinds of results globally,with poorer countries still lagging behind,and

189、as Omicron taught us,the world is not really out of the woods until vaccination levels reach these kinds of figures globally.But recent months have seen oral antivirals added to the armoury,so we really can have a fairly high degree of confidence that the pandemic phase of this infection is coming t

190、o an end.And pharma can take a huge amount of credit for this.It really did pull off a fantastic feat.The ability of our species to turn triumph into disaster can never cease to amaze,however.Having just about got through two years of pandemic,which was probably self-inflicted to some extent if the

191、coronavirus did indeed jump species due to illegal animal handling activities at that infamous Wuhan market,as I write in early March,the human race is now embarked on another colossal act of self-destruction,thanks to Russias invasion of Ukraine.This appalling aggression from Putins government has

192、brought war to Europe on a scale not seen since 1945,and is precipitating a humanitarian disaster.This will once again disrupt the global economy,and pharma will not escape unaffected.Also,as Russia becomes a pariah state,a significant market and territory for clinical trials may all but disappear.A

193、t least Western pharma companies are rising to the challenge of supporting Ukraine,with many announcing large financial donations or gifts of free medicines.Let us hope that this madness has ended by the time you read this.I was lucky enough to have a city break in Kyiv only three years ago,and it i

194、s a wonderful city,with a rich cultural landscape.I look forward to the day when it resumes its status as a top tourist destination,not a warzone.25But while Ukraine may be off the holiday list for a while,prevailing conditions elsewhere seem encouraging.Weve seen how China is exploding onto the glo

195、bal scene with a nascent pharmaceutical industry which is growing at such a rate that it is fast becoming a major power,and is now delivering its own homegrown new active substances.Might it single-handedly turbocharge pharma through the twenties and help it to navigate choppy waters elsewhere?I thi

196、nk its fair to say though,that as 2021 led the way in numbers of new NASs by a country mile,2022 might struggle to keep up the pace.But what is just around the corner,and if pharma continues to run a tight ship,might we be in the same boat next year?There are certainly plenty of candidates heading f

197、or the departure lounge to board pharma airways flights this year.My colleague Alex Shimmings,Executive Editor,Commercial R&D for Scrip Intelligence,always gets her crystal ball out for us here,and selects a minibus-full list of drugs waiting in the wings to dazzle us with their beach bodies through

198、 the coming year;these can be seen in Table 3.The brochure includes some novel NASs which we fully expect to grace the pages of this report next year.What became of our list of hotspots from last years report?Well,eight of the nine we highlighted as potential cultural highlights did indeed make it o

199、nto our 2021 NAS list,giving us a much better hit rate than the 50%from the previous year.The only drug to go missing in action is Pfizers atopic dermatitis therapy Cibinqo(abrocitinib),but this drug hasnt gone off the rails,as the company confirmed to us that it was expected to launch in February 2

200、022.The remainder Abecma,Aduhelm,Amondys 45,Bimzelx,Kerendia(finerenone),Lumakras,Nulibry,and Ukoniq have mostly already been covered in this report due to novelty or other features of interest.Whilst predictions are as likely to always come true as the weather is to be good on a UK staycation,plent

201、y of industry commentators seem to be as excited about the coming years for pharma as at any other time in recent history.Top of many peoples must-see attractions are forthcoming developments in oncology,and specifically immuno-oncology.TABLE 3:Selected important approvals/first launches expected in

202、 2022DRUGCOMPANYINDICATIONNOTESfezolinetantAstellasMenopause-related vasomotor symptomsOral neurokinin 3 receptor antagonistlenacapavirGileadHIV/AIDSFirst-in-class;Complete response letter received mosunetuzumabRocheFollicular lymphomaBreakthrough therapy designationoteseconazoleMycovia Pharmaceutic

203、alsVulvovaginal candidiasisFirst agent for the recurrent formsutimlimabSanofiCold agglutinin diseaseApproved Feb 2022tebentafuspImmunocoreUveal melanomaApproved Jan 2022tirzepatideEli LillyType 2 diabetes/obesityFirst glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 co-agonistzolbetuximabAst

204、ellasGastric cancerFirst-in-classSource:Pharmaprojects/Scrip,March 202226Quoted in a recent article in our commercial insights publication,Scrip,Paul Peter Tak,president and CEO of Candel Therapeutics,noted that:“In recent years,we have noticed that it is possible to cure a patient with cancer using

205、 immunological intervention with immune checkpoint inhibitors.This breakthrough provides proof of concept for what may be achieved with immunotherapy.At the same time,most patients still exhibit an inadequate response to treatment.New approaches,such as oncolytic viral immunotherapies,may help to te

206、ach the patients own immune system how to recognize and kill the tumor cells.”Kevin Lee,CEO of Bicycle Therapeutics,struck a similar chord,commenting that:“Most exciting for me are the discoveries uncovering the potential for new agents to act as catalysts for the immune system resetting the immune

207、environment and amplifying the benefit patients can gain from checkpoint inhibitors.Enabling unresponsive patients,or those who are no longer responsive after initial treatment,to become responsive,would mean no cancer patient is left behind.That will be the next significant milestone in our immunot

208、herapy research revolution.”Commentators are also suggesting that this decade could be the one where we crack some of the most perplexing conundrums which remain in neurological diseases.“Increased understanding of the complexity of the brain and its neurocircuitry will enable the industry to focus

209、on novel targets and bring forward much-needed therapeutic options to treat Parkinsons disease,epilepsy,and schizophrenia,”predicted Raymond Sanchez,chief medical officer at Cerevel Therapeutics.Maria Maccecchini,president and CEO of Annovis Bio,concurred,expecting“pivotal transformations to the neu

210、rodegenerative disease landscape”in 2022 and 2023,“including crucial data across the biotech and biopharma industries addressing Alzheimers disease and Parkinsons disease.”Lastly,infectious diseases continued to be at the forefront of many experts minds in the Scrip article,with COVID exerting both

211、positive and negative influences.Some,such as Andy Smith of Equity Development,predicted that the bottom might fall out of the COVID-19 vaccine market,as oral antivirals move to become standard-of-care.Others noted that vaccination may only be part of the solution,with Michael Skynner,Bicycle Therap

212、eutics COO,pointing out that:“We have had SARS,SARS2,MERS,Zika,HIV and Ebola in recent memory and there will be others to come.Being ready and quick to mobilize solutions is the future,and small molecule treatments are going to be part of that toolbox.”But the boost to new technologies which COVID a

213、ccelerated led to sunny forecasts from other experts,with the chief medical officer of Moderna,Paul Burton,pointing out that“the last two years have shown the opportunity that mRNA vaccines represent.”For the full article on industry insiders predictions on therapeutic area advances across the full

214、spectrum of pharma R&D,visit https:/So,despite everything which is going on in the world right now,we are completing our epic journey through pharma R&D country in an optimistic frame of mind.Invigorated by our international safari,we will have plenty of fond memories to cherish,and images to jog ou

215、r memories.Its been an exhausting couple of years for everyone,and 2022 is already throwing up fresh challenges.But a holiday also always makes us appreciate more what we have at home too.Its now time to put away the sun lotion and contemplate a mountain of dirty washing,before climbing up the woode

216、n hill to Bedfordshire to collapse tired but happy into the comfortable familiarity of our own bed.For pharma R&D in 202122 especially,but also for the entire past thirty years,its been quite a trip.Pharmaprojects has enjoyed being your tour guide,and will continue to support your journeys through t

217、he pipeline landscape in the year ahead.So,what do you reckon?Same time next year?27ABOUT THE AUTHORIan LloydSenior Director,Pharmaprojects&Data IntegrationIan Lloyd is the Senior Director of Pharmaprojects and Data Integration,overseeing the content and analyst services for our drug development sol

218、ution.He supports clients in their drug pipeline data requirements and inquiries,providing insight into the best search strategies to answer their drug-related business questions and also identifying and analysing trends in pharma R&D.For the past 30 years,he has authored the“Pharma R&D Annual Revie

219、w”and its new active substances(NAS)launches supplement.This has become a must-have industry report for those seeking to identify the changing fortunes of drug R&D.Ian joined Pharmaprojects in 1987,when it was part of PJB Publications.It was acquired by Informa in 2003.He previously worked in molecu

220、lar biology as a research assistant at the University of Bristol.Optimize your portfolio and licensing strategy with end-to-end intelligence for the global drug development pipelinePharmaprojects and Biomedtracker give you all the intelligence and analysis you need with the granular detail you want

221、to make better strategic decisions about your pipeline and portfolio.Do you need to know:What are the optimal in-and out-licensing opportunities for my business?1Who are my competitors and what are they doing in the market?2How many assets in the pipeline are likely to be approved and why?3What is t

222、he future market potential for drugs in the pipeline?4Together,Pharmaprojects and Biomedtracker form the leading end-to-end intelligence solution designed to help you understand the global drug development pipeline,competitive landscape and the so-what of your competitors drugs and trial milestones.THE SOLUTIONThe Pharma R&D Annual Review is here!SIGN UP TODAYDont miss our R&D Webinar on April 28th