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1、Global Trends in R&D 2023ACTIVITY,PRODUCTIVITY,AND ENABLERSFEBRUARY202 3As the global healthcare system re-equilibrates post-pandemic,the biopharmaceutical industry has resumed pre-COVID-19 levels of investment,pipeline activity,and launch of novel medicines following record breaking levels of each
2、in 2020 and 2021.Process and technology innovations that were accelerated by extreme circumstances during the pandemic are being integrated across the global pipeline and implemented as operational and organizational changes that are enabling ongoing productivity gains.This report assesses the trend
3、s in new drug approvals and launches,overall pipeline activity in terms of actively researched medicines,and the number of initiated clinical trials.It also profiles the state of R&D funding and the activity of companies of different types,and the results of research are compared to the input effort
4、 in a Clinical Development Productivity Index.This set of analyses reveals important shifts in therapeutic and geographic investments and ongoing prioritization of novel mechanisms of action,innovative development methods and accelerated regulatory pathways to optimize new therapy development and de
5、livery to patients.This work also examines changes in the Productivity Index driven by shifting pipeline complexity and probability of success.The research included in this report was undertaken independently by the IQVIA Institute for Human Data Science as a public service,without industry or gover
6、nment funding.The analytics in this report are based on proprietary IQVIA databases and/or third-party information and are not derived from proprietary sponsor trial information.The contributions to this report from Mohit Agarwal,Chris Bamford,David Cameron,Lucy Haggerty,Julia Kern,Bhagyashree Nawar
7、,Urvashi Porwal,Abhinandan Sarmah,Priya Srivastava,Tanushree Thakur,Terri Wallace and dozens of others at IQVIA are gratefully acknowledged.Find Out MoreIf you wish to receive future reports from the IQVIA Institute for Human Data Science or join our mailing list,visit iqviainstitute.org.MURRAY AITK
8、ENExecutive Director IQVIA Institute for Human Data ScienceIntroduction2023 IQVIA and its affiliates.All reproduction rights,quotations,broadcasting,publications reserved.No part of this publication may be reproduced or transmitted in any form or by any means,electronic or mechanical,including photo
9、copy,recording,or any information storage and retrieval system,without express written consent of IQVIA and the IQVIA Institute.Global Trends in R&D 2023:Activity,Productivity,and EnablersTable of ContentsOverview 2R&D funding 4R&D pipeline 12Clinical trial activity 23New drug approvals and launches
10、 33Clinical development productivity 40Productivity enablers 52Notes on Sources 66Methodologies 67References 68About the authors 69About the Institute 71aaaaaaaaaaaaaaaaaazR&D FUNDING The past year saw a restoration of pre-pandemic investment flows to life sciences companies in the U.S.after two yea
11、rs of heightened levels during the pandemic.U.S.focused biopharma investments declined 39%from a 2021 high,but at$42.1 billion,2022 investments remain 25%above the$27.3 billion in 2019.Over the past five years,deal activity has shifted geographically to include more companies headquartered in China
12、and Korea,and fewer Europe-based companies.While North American companies continue to execute the largest number of deals,these declined slightly over the five-year period.R&D funding from the large pharmaceutical sector remained high with a record$138 billion invested in R&D by the 15 largest pharm
13、aceutical companies in 2022.This represents an increase of 43%since 2017.The number of deals between pharma companies dropped by 25%from 2021 to 2022 with an increase in the share of deals involving emerging biopharma with larger companies.R&D PIPELINE The research and development pipeline remained
14、flat in 2022 with 6,147 products in active development from Phase I to regulatory submission,with growth slowing to 2%over the last two years but maintaining an 8.3%CAGR from 20172022.Oncology remains the focus of the pipeline,comprising 38%or 2,331 products and growing at 10.5%CAGR over the last fi
15、ve years with a recent shift to large-population solid tumor development contributing to the growth.Neurology continues to represent 11%of the pipeline,with research focused on Alzheimers and Parkinsons,and increasingly depression and other mental health conditions.Rare disease focus continues with
16、more than 1,800 molecules targeting one of the growing number of rare disorders for which there are often no or very limited therapeutics available.Half of these focus on oncology,and next-generation biotherapeutics account for at least a quarter of the rare-oncology products,with increased activity
17、 in CAR T and NK cell therapies,as well as gene editing and nucleic acid vaccines.Sources of industry scientific innovation continue to evolve with more than 2,800 companies or organizations currently contributing to the R&D pipeline.China-headquartered companies now account for 15%of the pipeline,u
18、p from 4%a decade ago,while Europes and Japans shares have fallen to 23%and 6%,respectively.Emerging biopharma companies(EBPs)are responsible for two-thirds of the molecules in the R&D pipeline,up from 51%in 2017 and one-third in 2002.U.S.and China-headquartered companies account for the largest sha
19、re of the EBP pipeline at 46%and 20%respectively.CLINICAL TRIAL ACTIVITY Clinical trial activity was remarkably resilient even as the pandemic stretched through 2022,with a 2%decline in non-COVID-19 trial starts over 2021 and an increase of 8%over 2019 activity.COVID-19 trials,which surged dramatica
20、lly in 2020,have dropped to less than half the 2020 level as the severity of the pandemic has subsided.2022 saw a continued acceleration of mRNA vaccine trial activity led by continued focus on COVID-19 but expanding to meaningful development in multiple other disease areas.Oncology remains the ther
21、apeutic area with the most clinical trial activity in 2022,accounting for 40%of trial starts.Within oncology,rare disease starts have been variably up and down in the past four years,while non-rare oncology has been consistently growing oncology non-rare represented 44%of the oncology trial starts i
22、n 2022,which is the highest relative level in the past 10 years.Many of the other therapeutic areas showed a slight decrease in clinical trial starts in 2022 versus 2021,but in most cases,remained close to 2019 levels suggesting a re-equilibration to pre-pandemic growth patterns.Exceptions to this i
23、nclude ophthalmology,womens health,and infectious disease where trial starts matched or slightly exceeded 2021 levels.Notably,though neurology dropped slightly,depression trial starts are 68%higher than pre-pandemic with novel mechanisms,including psychedelics,being tested in at least 35%of 2022 tri
24、als.2|Global Trends in R&D 2023:Activity,Productivity,and EnablersOverviewaaaaaaaaaaaaaaaaaazAcross completed clinical trials,Black/African American and Hispanic patient representation has declined over the past decade with Black/African American inclusion dropping 42%in the past two years and remai
25、ns below U.S.demographic levels for many therapeutic areas including cardiovascular,endocrinology,neurology,and oncology even in trials with only U.S.sites.NEW DRUG APPROVALS AND LAUNCHES A total of 64 novel active substances(NAS)launched globally in 2022,a decline from the more than 80 launched in
26、each of the prior two years but representing a return to pre-COVID-19 levels.Declines were driven by fewer COVID-19 vaccines and therapeutics,fewer U.S.accelerated approvals,and fewer NAS launched only in China.A growing share of new launches in 2022 were first-in-class,reflecting the increasing ava
27、ilability of novel science for patients.2022 also saw continued growth in number of specialty medicine launches.As new medicines have increasingly targeted areas of high unmet need,clinical trial designs have used single-arm and open label designs and have been used in the approval trials for 43%of
28、launches over the past 5 years.A total of 353 novel active substances have launched globally in the past 5 years,bringing the 20-year total to 903,with variations in timing of launch and access to these medicines across major geographies.Emerging biopharma companies originated 67%of all new drugs in
29、 2022 and launched 69%of those,indicating more independence on the part of these companies in taking products from innovation to market.CLINICAL DEVELOPMENT PRODUCTIVITY Based on the IQVIA Institute Clinical Development Productivity Index which provides a composite metric of success rates,clinical t
30、rial complexity and trial duration clinical development productivity increased dramatically in 2022 driven by a decrease in complexity as the pipeline moved away from large COVID-19 focused trials.Specifically,the complexity metric returned to its pre-pandemic trend following a significant increase
31、largely driven by very high subject enrollment across COVID-19 trials in 2021.The declining number of sites for rare diseases and oncology trials in 2022 is another key driver of the decrease in overall pipeline complexity.The composite success rate across all therapy areas fell to 6.3%in 2022 while
32、 phase II and III success rates rose 26%.At the same time,trial durations have increased slightly over the past decade,though oncology and rare diseases trial durations have been declining in recent years,attenuating overarching trial duration increases.PRODUCTIVITY ENABLERS As technology and data i
33、nnovations take hold across the pharmaceutical development pipeline,productivity is being impacted by a range of trade-off effects on complexity,timing and probability of success.Scientific complexity continues to increase with first-in-class mechanisms in 62%of the launches spread across nearly all
34、 major therapeutic areas in 2022.Likewise,ongoing regulatory shifts are resulting in a rapidly evolving landscape for innovators.Enablers including novel trial designs and remote,virtual or decentralized trials are playing an increasing role in the recent pipeline.Both advances in trial execution ar
35、e associated with more subjects,sites,countries,and endpoints suggesting more complex execution,but both are expected to yield decreases in clinical program duration over traditional trials.Most new drugs in 2022 received expedited reviews with increases in priority and breakthrough designations whi
36、ch,on average,include relatively fewer patients and therefore lower trial complexity.Additionally,the median time from first patent filing to launch for U.S.NAS remained near the lowest levels for the decade in 2022 at 11.2 years,in line with productivity enablers helping to bring industry developme
37、nt timelines down.Looking forward,less mature enablers are showing increasing potential for impact on clinical development productivity as evidenced by the advance of innovative AI/ML enabled research candidates into the clinical development pipeline.iqviainstitute.org|34|Global Trends in R&D 2023:A
38、ctivity,Productivity,and Enablers Biopharma investment flows and deal activity in life sciences companies in the U.S.were restored to pre-pandemic levels after two years of heightened activity during the pandemic.Venture capital investments into U.S.companies declined 39%in 2022 but remain 25%above
39、2019 levels,while investments into European companies declined 74%in 2022 and are 47%below 2019 levels.U.S.venture capital deal activity and investment flows remain high at$42.1Bn,down from$54.8Bn in 2021 but above the$27.3Bn in 2019.Over the past five years,deal activity has shifted geographically
40、to include more companies headquartered in China and South Korea and fewer Europe-based companies.While North American companies continue to represent the largest number of deals,they declined slightly over the five-year period.Deal activity in 2022 returned to pre-pandemic levels,with a 25%contract
41、ion of R&D collaboration versus 2019.The 15 largest pharmaceutical companies invested a record$138Bn in 2022 in R&D expenditure,an increase of 43%since 2017 and representing 18.8%of their recorded sales.The number of deals between pharma companies dropped by 25%from 2021 to 2022,with an increase in
42、the percentage of deals involving emerging biopharma with larger companies.R&D fundingThe past year saw a restoration of pre-pandemic investment flows to life sciences companies in the U.S.after two years of heightened levels during the pandemic.iqviainstitute.org|5Notes:Biopharma funding is related
43、 to a set of recipient companies globally defined by the Bioworld.IPO means initial public offering;Follow-on refers to a public offering of shares that is not the first one;Public/other financings are when public companies receiving financing in some other way;Private means venture capital investme
44、nts.R&D FUNDINGBiopharma funding levels slowed in 2022 but still exceed the 2019 level Biopharma funding including IPOs,follow-on funding,and venture capital investment slowed in 2022 after two years of heightened levels during the pandemic.The level of activity still exceeds the 2019 level,although
45、 the mix of funding types has shifted,and IPO activity was notably lower.The shifts in deal activity reflect changes in the types of companies being invested in,their therapeutic focus,and where they are located.Start-ups with a focus in COVID-19 had seen funding expand during 2020 and 2021 but slow
46、ed in the most recent months.Companies headquartered in China and Europe have seen deals slow more dramatically than those in the U.S.Exhibit 1:Biopharma funding levels US$Bn,20132022Source:BioWorld,accessed Jan 18,2023.Follow-onsPublic/otherPrivateTotalIPOs200002237
47、66544733271628402222.037.068.437.651.867.057.9134.5118.460.8020406080100120140Values US$Bn 6|Global Trends in R&D 2023:Activity,Productivity,and Enablers For companies receiving funding,those located in the U.S.rose sharply in 2020 and 2021,while dropping
48、as a share of overall deals as a result of rising levels of funding in Europe,China and other countries.U.S.companies saw funding levels drop by 39%in 2022 compared to the prior year,while still being 25%higher than the 2019 level.European companies saw funding more than double in 2020 from the 2019
49、 level but have seen that drop in the two years since.In 2018 and 2019,European companies received an average of$15.2Bn total funding,while the 2022 level is about half that level at$7.8Bn.The three-year average for 20202022 now exceeds$26Bn.Companies based in China saw their share of deals and abso
50、lute value jump in 2020 and 2021 and then drop by 59%in 2022 to a level that is 11%below the 2019 level.It remains to be seen if the 2022 share of deals by geography is a correction to unusual trends during the pandemic or a more sustained shift for these key hubs for innovation.Exhibit 2:Biopharma
51、funding levels by company location,20182022Notes:Biopharma funding is related to a set of recipient companies globally defined by the Bioworld.Company location is based on the recipient headquarters.R&D FUNDINGBiopharma funding has shifted away from China and Europe in 2022Source:BioWorld,accessed J
52、an 18,2023.EuropeChinaOtherUS0%10%20%30%40%50%60%70%80%90%100%200212022Values US$Bn 67.057.9134.5118.460.8iqviainstitute.org|7 Venture capital deal activity and investment flows in the U.S.accelerated in the past three years as interest in life sciences intensified,with more than 2,000 de
53、als and$42Bn of deal value occurring in 2022,down from the level in 2021 but still far above pre-pandemic levels.Life sciences venture capital deals continue to grow,with an uptick in investment in later-stage deals which typically draw more dollars and show a 10%CAGR increase since 2017 compared to
54、 only 5%CAGR for the five years through 2019.The total number of deals peaked at 2,588 in 2021 21%higher than 2020 but dropped 22%in 2022 to 2,009 deals,only slightly above the 1,994 in 2019.Deal value jumped in 2020 and has remained elevated since,with 2022 at$42.1Bn,54%higher than the 2019 level.T
55、he escalation of deal value in 2020 and into 2021 represents a significant shift in trajectory and reverses a flat-to-declining trajectory from 2018 to 2019.The number of angel and seed deals dropped sharply in 2022 to 586 after higher deals of 710 and 799 in the prior two years,far above the previo
56、us trend.Exhibit 3:U.S.life sciences venture capital deal value in US$Bn and number of deals closed by type,20132022Notes:U.S.Life Sciences venture capital funding deals is more inclusive than global biopharma analysis in earlier exhibits by including only U.S.-based companies as well as including l
57、ife sciences companies in adjacent sectors including service providers to involved companies,drug distribution,care delivery,and insurers.VC=Venture Capital.Deals involve companies defined as life sciences which includes a range of biopharma,healthcare delivery and distribution and other types of co
58、mpany.R&D FUNDINGU.S.venture capital deal activity and investment flows remain high as interest in life sciences continuesSource:PitchBook-NVCA Venture Monitor Q4 2022,accessed January 2023.Available from:https:/ deal countAngel&seed deal countLater VC deal countEarly VC deal countVenture growth dea
59、l countTotal deal value($Bn)$11.4$14.3$16.5$15.7$20.6$28.5$27.3$40.7$54.8$42.105001,0001,5002,0002,5003,000002000022Deal countsDeal value US$Bn 8|Global Trends in R&D 2023:Activity,Productivity,and Enablers North America represents the largest global clust
60、er of life sciences entrepreneurship and as a result includes 57%of deals in 2022,dropping from 62%in 2017.Total deals between companies involving the region dropped by 355 or 13%over the five-year period.Since 2017,the level of deal activity has shifted considerably,with rising activity from compan
61、ies headquartered in South Korea and China.There were 387 total deals in China in 2022,up 33%from five years earlier,reflecting a significant increase in the level of interest in the innovations from these companies and many including high profile large pharma collaborations or licensing deals,and t
62、he near-term expectation that some of these medicines will be approved in the U.S.and other major developed markets.The increasing deal volume with South Korean companies is greater than with Chinese companies,growing from 251 five years ago to 490 in 2022,but involving a greater share of licensing
63、and collaborative R&D deals building on the established biologic and biomarker capabilities of key companies along with well placed regional capacity for manufacturing,including biosimilars.Deals involving European companies dropped by 163 or 9%,while share of activity dropped from 41%to 39%as the r
64、ate of activity failed to keep pace with the increases from the more active Asian companies.Exhibit 4:Change in deals involving companies headquartered in various geographies,20172022Notes:Deals by company headquarter location between pharma companies and are not mutually exclusive.Total deals inclu
65、de double-counts of deals where participants are in different regions.Excludes venture capital and funding deals.Funding deals are defined as those which include grants and awards from governments,etc.R&D FUNDINGDeal activity has significantly increased in Korea and China over the past five years wi
66、th US,Europe and Japan decliningSource:IQVIA Pharmadeals,Dec 2022.5,-163-88105,6002017U.S./CanadaSouth KoreaChinaEuropeJapanAll others2022Number of deals6,0005,9005,8005,7005,6005,5005,4005,3005,2005,1005,000iqviainstitute.org|9 Overall,there was a decrease in activity across all deal ty
67、pes in 2022,driven by hesitancy toward dealmaking related to geopolitical tensions,drug pricing and macro-economic issues(fluctuating valuations,inflation).Publicly disclosed life sciences deal activity reveals that the number of agreements signed in 2022,excluding standalone research grants,was app
68、roximately 1.5%above the 2019 level and 16.5%lower than 2021.In 2021 there were 519 COVID-19-related deals,dropping to 286 in 2022 as there were fewer perceived new opportunities in either vaccines or therapeutics.While the rising number of deals was driven by COVID-19 in 2020 through 2022,the 4,339
69、 non-COVID-19 deals in 2021,were 9%higher than 2019,and the 3,770 non-COVID-19 deals in 2022 was 6%lower than 2019,reflecting a return to previous trends.General market volatility and prospect of increased regulatory scrutiny led to a significant cooling of appetite for M&A deals.The M&A process had
70、 initially been reported to be hindered by a lack of face-to face contact,particularly for larger deals,which resulted in delays but did not stop the signing of new deals.Much of the industry had returned to in-person meetings at many conferences in 2022.There were 483 M&A deals announced in 2022,do
71、wn from 615 in 2021(defined here as Mergers,Business Acquisitions and Divestments,signed but not necessarily completed)but matching the number in 2018.Exhibit 5:Number of life sciences deals and share by type,20182022Notes:Life sciences deals disclosed and categorized by type,excluding funding deals
72、.R&D FUNDING2022 deal activity returned to pre-pandemic levels with a 25%contraction of R&D collaboration versus 2019Source:IQVIA Pharmadeals,Dec 2022.LicensingCollaborative R&DCollaborative R&D and licensingOthersM&A0%10%20%30%40%50%60%70%80%90%100%2002120224,1853,9954,9924,8584,05610|Gl
73、obal Trends in R&D 2023:Activity,Productivity,and Enablers The largest pharmaceutical companies together spent more than$138Bn on research and development in 2022,up 1.7%from 2021.Across these companies,R&D dropped to 18.8%of revenue in 2022 after four years above 19%but remains at historically high
74、 levels.Global revenue for these 15 companies totaled$737Bn in 2022,up from$704Bn in 2021,a 4.7%increase in net sales.The reduction in R&D%of revenue in 2022 is attributed to fewer companies having major write-offs from failed R&D programs,and some large companies having a major increase in sales re
75、lated to COVID-19 vaccines or therapeutics while their R&D spending also increased,but at a slower rate.Since 2017,R&D spending for large companies has increased by 43%with a five-year CAGR of 7.4%.R&D expenses can include write-offs of failed R&D programs developed internally or acquired,which can
76、bring year-to-year variability in the level of total spending.Exhibit 6:Large pharma R&D spending and spending as a percentage of sales 20132022*,US$BnNotes:*Based on financial reporting for twelve months ending Sep 30,2022 for all companies except Roche which is based on 12 months ending Jun 30,202
77、2.All other years reflect total R&D for the calendar year indicated.CAGR=Compound annual growth rate.Companies include:AbbVie,Amgen,AstraZeneca,Bristol Myers Squibb,Eli Lilly,Gilead,GlaxoSmithKline,Johnson&Johnson,Merck,Novartis,Novo Nordisk,Pfizer,Roche,Sanofi,and Takeda.These represent the total c
78、ompany view,and some divisions such as consumer health are typically less R&D-intensive than the pharmaceutical division.The total expenditure is as reported by companies in their financial statements.R&D FUNDINGR&D expenditure by large pharma corporations totaled a record$138Bn in 2022*,an increase
79、 of 43%since 2017Source:Company financial statements;IQVIA Institute,Jan 2023.R&D spending as a percentage of salesR&D spending848287869297613816.6%17.2%17.5%18.2%18.7%19.6%19.3%20.4%19.3%18.8%2000022*iqviainstitute.org|11 Emerging biopharma companies-defi
80、ned as those with less than$200Mn in R&D spending and less than$500Mn per year in annual sales have expanded their involvement in deals steadily over the past five years.In 2017,large and-mid-sized companies those with more than$5Bn in global sales were involved in 46%of deals that involved other la
81、rge and mid-sized or emerging companies;while that level of deals has remained steady,as a share of the company deal activity,it has dropped to 42%.The shifts in activity over the past five years have meant that 90%of all deal activity between these types of companies involves an emerging company,up
82、 from 84%five years ago,even as the activity between emerging companies without a larger firm now represent 57%of deals,up from 53%five years ago.The rising independence of emerging biopharma companies in recent years,shifted in 2022 as deals involving larger companies jumped from 27%in 2021 to 33%i
83、n 2022.Even so,novel drugs developed by emerging biopharma are also being launched by them more often,with 69%of the 26 EBP-originated NAS launches in the U.S.in 2022 also being launched by an EBP(Exhibit 31).Notes:Deals in this analysis exclude funding deals.Funding deals are deals that involve res
84、earch grants or funding from government institutions,government bodies,universities or other academic institutions.Excludes VC and funding grants from non-commercial.Exhibit 7:Number and share of deals by company segment,20172022R&D FUNDINGDeals between pharma companies dropped by 25%from 2021 to 20
85、22,mostly in EBP-only deal activitySource:IQVIA Pharmadeals,Dec 2022.Total selectedcompany-to-company dealsLarge/mid companies with EBPLarge/mid companies with another large/midEBP-EBP9411,0901,1181,4031,4961,13205001,0001,500200202021202253%52%56%59%64%57%31%32%30%29%27%33%15%16%14%12%10
86、%9%12|Global Trends in R&D 2023:Activity,Productivity,and Enablers The research and development pipeline remained flat in 2022,with 6,147 products in active development from Phase I to regulatory submission,growing 2%over the last two years,but 49%since 2017.The clinical development pipeline for non
87、-rare cancers grew 7%in 2022,however development for rare cancers has plateaued or declined slightly since 2020,which may reflect the beginning of a shift away from rare cancers by pharmaceutical companies.Oncology development is focused more on solid tumors,with 5%growth over the last year,while de
88、velopment of drugs for hematological cancers declined 4%in 2022.Neurology research is focused on Alzheimers and Parkinsons,with depression and other mental health conditions becoming increasingly more important.The focus on rare diseases beyond rare cancers is reflected in the R&D pipeline,which inc
89、ludes more than 900 molecules targeting one of the growing number of rare disorders for which there are often no or very limited therapeutics available.More than 900 next-generation biotherapeutics are now in the R&D pipeline,with increased activity in CAR T and NK cell therapies as well as gene edi
90、ting and nucleic acid vaccines.More than 40%of next-generation biotherapeutics in development in 2022 were for oncology,bringing great promise for cancer treatment.More than 2,800 companies or organizations currently contribute to the R&D pipeline.China-headquartered companies now account for 15%of
91、the pipeline,up from 4%a decade ago,while Europe and Japans shares have fallen to 23%and 6%,respectively.Emerging biopharma companies(EBPs)defined as those with R&D spending less than$200Mn per year and less than$500Mn in annual sales are responsible for two-thirds of the molecules in the R&D pipeli
92、ne,up from 51%in 2017 and one-third in 2002.Emerging biopharma drug development is rising rapidly,particularly in China-headquartered companies,whose share now exceeds that of Europe.U.S.-headquartered companies represent nearly half of EBP development,while Europe and Japan have seen declining shar
93、es of the EBP pipeline over the last decade.R&D pipelineThe research and development pipeline remained flat in 2022 with ongoing oncology focus and continued share gain in rare,next-generation,Chinese and EBP segments of the pipeline.iqviainstitute.org|13Notes:Includes drugs with an active research
94、program,with phase determined by the highest phase of research regardless of indication.Oncology includes supportive care.Neurology includes central nervous system disorder treatments and mental health treatments but does not include pain management or anesthesia.R&D PIPELINEGrowth in the clinical p
95、ipeline has remained flat since 2020,although 49%above 2017 levels The research and development pipeline remained flat in 2022,with 6,147 products in active development from Phase I to regulatory submission,growing 2%over the last two years and 49%since 2017.This slowing growth since the pandemic be
96、gan is likely due to delays in development activity as COVID-19 and new variants have caused a series of disruptions to society since 2020.Oncology remains the focus of the pipeline,comprising 38%or 2,331 products and growing at 10.5%CAGR over the last five years.Neurology continues to represent 11%
97、of the pipeline,with growth in the number of products in development to 699 following a modest decline in 2021.The therapy area with the highest CAGR since 2017 is eye and ear conditions(20.7%),which is predominantly focused on ocular anti-neovascularization products and treatments for rare eye cond
98、itions.Vaccines have the second-highest CAGR since 2017(14.1%),with a heavy focus on COVID-19 vaccines and influenza in recent years.Products in development for gastrointestinal disorders account for 7%of the pipeline,growing 9.9%CAGR over the last five years.There has been an increased focus on rar
99、e gastrointestinal conditions and liver disease.Exhibit 8:Number of pipeline products Phase I to regulatory submission by therapeutic drug class,20122022Source:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.8405001,0001,5002,0002,5003,0003,5004,0004,5005,0005,5006,0006,500201220132014
100、2000212022GastrointestinalCardiovascularDermatologicsImmunology/AllergyVaccinesEye/EarOncologyInfectious diseaseNeurologyHematologicsGenitourinary/Womens healthRespiratoryEndocrinologyPainAll others14|Global Trends in R&D 2023:Activity,Productivity,and Enablers The clinical dev
101、elopment pipeline for non-rare cancers grew 7%in 2022,however development for rare cancers has plateaued or declined slightly since 2020,which may reflect the beginning of a shift away from rare cancers by pharmaceutical companies.In 2022,39%of the oncology pipeline was under development for rare ca
102、ncers,down from 41%in 2021 and 46%five years ago.Targeted small molecule and biotech therapies continue to grow in development for non-rare cancers but have seen limited growth and even declines in rare cancers.These include many of the new immuno-oncology treatments,checkpoint inhibitors,and kinase
103、 inhibitors.Although next-generation biotherapeutics represent a smaller share of the total oncology pipeline,these cell,gene,and RNA therapies provide promising tools for more precision in cancer treatment,particularly in rare cancers where one-quarter of products under development are next-generat
104、ion.As many of these targeted or next-generation treatments relate to genetic mutations or other biomarkers,the use of companion diagnostics is likely to become more prevalent to provide more precise and effective treatment in cancer patients.Exhibit 9:Number of Phase I to regulatory submission onco
105、logy pipeline products by type,20122022Notes:Analysis includes medicines in active research with a focus on cancer therapeutics including supportive care.Medicines are considered targeted if their mechanism of action uses a specific biomarker to target treatment within the body.Many cancer drugs hav
106、e multiple tumors in research,and drugs which have any trials focused on rare cancers have been included as rare.Drugs which have no rare tumor targets are considered non-rare.All other includes a range of cytotoxic,hormonal,and radiotherapeutic mechanisms without a targeting mechanism.R&D PIPELINET
107、he clinical pipeline for large population cancers continued to grow in 2022,while rare cancers peaked in 2020Source:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.02004006008001,0001,2001,400200001820202022Rare cancersNon-rare cancers Targeted small mo
108、leculesNext-generation biotherapeuticsTargeted biotechAll othersiqviainstitute.org|15 Oncology research and development has seen an increasing focus on targeted drugs,with innovative mechanisms of action for treatment of cancers over the last decade.While development of drugs for hematological cance
109、rs declined 4%in 2022,clinical development for solid tumor cancers grew 5%following a slight contraction in the pipeline in 2021.Next-generation biotherapeutics are increasingly under investigation for hematological cancers,with the number of products currently in active research more than four time
110、s what it was in 2017 and accounting for 28%of the hematological-oncology pipeline.Immuno-oncologics,which saw significant growth over the last decade,have begun to taper off in recent years,with declines in hematological cancers beginning in 2018 and in 2019 for solid tumors,potentially indicating
111、a switch to even newer targeted molecules.Despite being first developed in the 1960s,bispecific antibody development for cancer treatment was minimal a decade ago and has grown significantly,now representing 7%of both the hematological-oncology and solid tumor pipelines,indicating an increasing focu
112、s on the ability of these molecules to act on multiple targets or through different mechanisms of action.Many new antibody-drug conjugates have been under development in oncology in the last decade,allowing for targeting cytotoxic agents directly to cancer cells,improving on the non-specificity of o
113、lder oncology products.Exhibit 10:Oncology R&D pipeline Phase I to regulatory submission by type,20122022Notes:Other includes non-targeted mechanisms within categories of cytotoxics,hormonal,and radiotherapeutics.Products being investigated for more than one type of cancer may be included in both he
114、matological and solid tumor cancers.R&D PIPELINEOncology development is focused on solid tumors,with next-generation biotherapeutics growing across all cancersSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.8402004006008001,0001,2001,4001,6001,8002,0002001820202022 20
115、01820202022Hematological cancersSolid tumor cancersProtein kinase inhibitorsAntibody-drug conjugatesBispecific antibodiesImmuno-oncologicsNext-generationbiotherapeuticsOther biologicsOther targeted small moleculesAll others16|Global Trends in R&D 2023:Activity,Productivity,and Enablers Th
116、ere are currently 699 products under investigation in the neurology pipeline,including products to treat neurodegenerative,neuromuscular,and psychiatric disorders.Much of the ongoing research is focused on Alzheimers and Parkinsons diseases,with 127 and 96 products under investigation,respectively.C
117、urrent marketed products for Alzheimers disease are focused on symptom management,with recent exceptions including aducanumab and lecanemab;however,most of the products under clinical development are disease modifying.Depression and other mental health conditions have become more prevalent and recog
118、nized,particularly during the pandemic1,and account for an increasing amount of the neurology pipeline,with 84 products under development for depression and 31 for anxiety.Other rare neurological diseases,such as amyotrophic lateral sclerosis(ALS)and Duchenne muscular dystrophy,continue to receive a
119、ttention in the pipeline,with promising therapies in development.Currently,72%of the neurology pipeline consists of small molecule products,indicating their continued utility in a rapidly evolving space.Next-generation biotherapeutics,such as cell and gene therapies,are increasingly being investigat
120、ed for neurologic conditions,comprising 11%of the pipeline.These products could show the most promise for treating some of these debilitating diseases.Exhibit 11:Number of products in neurology Phase I to regulatory submission pipeline in 2022 by disease and therapy typeNotes:Analysis includes produ
121、cts in active research with a focus on neurology therapies.Products being investigated for more than one indication may be included in more than one disease area.Therapy types are non-overlapping and macromolecules(biologics)are those biologic products that are not otherwise noted.Percentages may no
122、t sum to 100%due to rounding.R&D PIPELINENeurology research is focused on Alzheimers,Parkinsons and depression,with a range of other often rare diseasesSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.0204060800Smallmolecule72%Biologic16%4%,Cell therapy4%,Gene therapy3
123、%,RNA therapy1%,Other NGBn=699Select disease areas Therapy typeAlzheimersParkinsonsDepressionMultiple sclerosisALSSchizophreniaDrug addictionEpilepsyAnxietyOther neuromuscularSleep disorderMigraineHuntington diseaseAutismDuchenne muscular dystrophyiqviainstitute.org|17 Currently,there are 1,824 prod
124、ucts(30%of pipeline)under development for rare diseases,with half of these for diseases outside of oncology.Phase II makes up a significant portion of the pipeline,reflective of significant numbers of hybrid Phase I/II trials underway with difficult to identify patients,extending their trial duratio
125、ns and contributing to potentially different clinical development journeys for these products.Products in development for rare neurological disorders represent the largest share of the rare disease pipeline after rare oncology,accounting for 22%;however,this share declines in later phases and has re
126、mained stable over time,indicating difficulties in achieving success in earlier phases for these products.Across phases,drug development for rare gastrointestinal conditions has been increasing now accounting for 16%of rare drug development.Nearly half of the rare gastrointestinal pipeline is for tr
127、eating inherited rare disorders such as lysosomal storage disorders,mucopolysaccharidosis,and Pompe disease,with a high number of gene therapies and other next-generation biotherapeutics to address the underlying genetic modifications for these disorders.Exhibit 12:Rare disease pipeline excluding on
128、cology,by phase and therapeutic drug classNotes:Includes drugs with an active research program,with phase determined by the highest phase of research regardless of indication.Many drugs have ongoing research for multiple indications,and drugs which have any trials focused on rare diseases have been
129、included as rare.Analysis excludes oncology.R&D PIPELINE38%of development for rare diseases outside of oncology is focused on gastrointestinal and neurologic diseasesSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.Phase lPhase llPhase lllPre/Registration0%10%20%30%40%50%60%70%80
130、%90%100%200022Share of products by yearP h e sa IP h e saI I P h e saI I I e R/e rPa r ts i go i t nPhase IPhase IIPhase IIIPre/Registrationn=209n=419n=226n=51CardiovascularInfectious diseaseEye/EarImmunology/AllergyHematologicsNeurologyRespiratoryGastrointestinalVaccinesAll ot
131、hersDermatologicsGenitourinary/Womens healthPain18|Global Trends in R&D 2023:Activity,Productivity,and Enablers In 2022,960 next-generation biotherapeutics were in development from Phase I through filing with a regulatory agency.The next-generation biotherapeutic pipeline has grown significantly in
132、recent years,with a 20%CAGR since 2017.Cell therapies represent the largest share of the next-generation biotherapeutic pipeline with 40%of these being investigated for a range of cancers,predominantly non-rare solid tumor malignancies.Gene therapies,including gene editing technologies such as CRISP
133、R,have had moderate growth in recent years following a period of deceleration in the early-2010s.26%of these are focused on gastrointestinal conditions and eye and ear conditions representing another 16%.Even though they were not in development prior to 2012,there are now 217 chimeric antigen recept
134、or T-cell(CAR T-cell)and natural killer(NK)cell therapies in development,representing the second highest share of the next-generation biotherapeutic pipeline,with nearly all in development for cancer.RNA-based therapeutics,including RNA interference(RNAi)the inhibition of expression of certain genes
135、 by mRNA continue to represent a small share of the next-generation biotherapeutic pipeline.RNA and DNA vaccines have become increasingly investigated since the COVID-19 pandemic across a range of cancers and infectious diseases(Exhibit 21).Exhibit 13:Next-generation biotherapeutics Phase I to regul
136、atory submission pipeline by mechanism,20122022Notes:Includes drugs with an active research program,with phase determined by the highest phase of research regardless of indication.Other includes oligonucleotides and other less common next-generation biotherapeutics.R&D PIPELINEThe next-generation bi
137、otherapeutic pipeline is focused on gene editing,CAR T-cell and other cell therapiesSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.20000212022RNA therapeuticsRNA/DNA vaccineGene editing&gene therapyCAR T-cell&NK cell therapyCell therapy020040060
138、08001,0001,200Otheriqviainstitute.org|19 More than 85%of the next-generation biotherapeutic pipeline is in Phase I or II,with smaller portions in Phase III and submitted for regulatory review,highlighting the challenges of getting these products to the market.Next-generation are defined as cell ther
139、apies,gene therapies,gene editing,nucleotide and RNA interference,mRNA therapies and RNA or DNA vaccines.Oncology continues to comprise the bulk of next-generation biotherapeutic development(42%),however other disease areas,such as gastrointestinal conditions and neurological disorders,continue to s
140、ee increasing activity.Next-generation vaccines have seen a substantial increase in the last two years,driven by the pandemics acceleration of mRNA and DNA vaccine technology development.Although COVID-19 remains the focus of these nucleic acid vaccines,these are now being tested for other diseases(
141、Exhibit 21).Exhibit 14:Next-generation biotherapeutic products pipeline by phase and therapeutic drug class Notes:Includes drugs with an active research program,with phase determined by the highest phase of research regardless of indication.R&D PIPELINEMore than 40%of next-generation biotherapeutics
142、 in development in 2022 were for oncology and in earlier stagesSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.Phase lPhase llPhase lllPre/Registration0%10%20%30%40%50%60%70%80%90%100%200022Share of products by yearPhase IPhase IIPhase IIIPre/Registrationn=
143、392n=449n=91n=27PainCardiovascularInfectious diseaseEye/EarImmunology/AllergyHematologicsNeurologyRespiratoryGastrointestinalOncologyEndocrinologyVaccinesAll othersDermatologicsGenitourinary/Womens health20|Global Trends in R&D 2023:Activity,Productivity,and Enablers Currently,more than 2,700 compan
144、ies and more than 100 academic or research groups around the world are involved in the R&D pipeline.The U.S.share of the global R&D pipeline has remained relatively stable,at above 40%over the past 15 years.Europes share has declined from 31%to 23%over the past 15 years,while the absolute number of
145、active programs grew by 25%from 1,327 to 1,655.Companies headquartered in Japan have seen a declining share of the pipeline,dropping to 6%in 2022,down from 10%five years ago,and a 26%drop in absolute number of active programs since 2017.Products from China-headquartered companies now represent 15%of
146、 the R&D pipeline,up from 6%five years ago and 2%in 2007.The active pipeline from China-headquartered companies has more than tripled in the last five years,reflecting recent significant investments made in the life sciences there.South Koreas share of the pipeline has remained relatively stable des
147、pite 92%growth in the absolute number of active programs over the last five years.Exhibit 15:Number of drugs over time and country share of pipeline Phase I to regulatory submission based on company headquarters location,20072022Notes:Includes drugs with an active research program,with phase determi
148、ned by the highest phase of research in each year regardless of indication.Each company involved in a drugs development is counted individually,so products with more than one company involved are counted more than once and may be included in more than one region.Europe is defined as any country in c
149、ontinental Europe.R&D PIPELINEDrugs from China-headquartered companies have risen to 15%of the pipeline from 4%a decade agoSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.EuropeJapanChinaSouth KoreaU.S.All others01,0002,0003,0004,0005,0006,0007,0008,0002007200%42%44%4
150、4%31%30%27%23%11%12%10%6%2%4%6%15%3%3%3%5%0%5%10%15%20%25%30%35%40%45%50%2007201220172022iqviainstitute.org|21 The contribution of emerging biopharma companies those with less than$500Mn in annual sales and R&D spending less than$200Mn per year continues to increase,while large pharma companies thos
151、e with greater than$10Bn in annual sales represent an increasingly smaller share of the R&D pipeline.While emerging biopharma companies were responsible for only one-third of innovation in 2002,they now are responsible for two-thirds of the R&D pipeline,highlighting the increasing importance of inno
152、vation from these smaller companies.While the number of larger companies actively involved in the R&D pipeline has remained stable since 2017,the number of emerging biopharma companies has grown 26%.Large pharma companies now represent just 23%of pipeline activity,down from 48%in 2002,while the abso
153、lute number of actively researched drugs rose from 956 to 1,090 for companies of this size.Although a small contributor to the clinical pipeline(1%),academic and research groups play an important role in the R&D pipeline,particularly in advancing work in discovery and pre-clinical phases prior to cl
154、inical investigation.Exhibit 16:Share of Phase I to regulatory submission pipeline by company segment,20022022Notes:Includes drugs with an active research program,with phase determined by the highest phase of research regardless of indication.Company segment when two or more companies are involved i
155、s determined by the larger sales segment.R&D PIPELINEEmerging biopharma companies are responsible for two-thirds of the R&D pipeline,with their share continuing to growSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.SmallLargeMidAcademicEBP0%10%20%30%40%50%60%70%80%90%100%200220
156、042006200820002222|Global Trends in R&D 2023:Activity,Productivity,and Enablers Emerging biopharma company R&D activity is spread out across major geographies,with more than 4,500 products under development by emerging biopharma companies.The emerging biopharma pipeline grew 7%
157、in 2022,following a slight plateau in 2021 due to the pandemic,bringing total growth since 2017 to 82%.China-headquartered companies now represent 20%of the global emerging biopharma pipeline,up from 9%just five years ago and higher than Chinas share of the overall pipeline.Growth in the emerging bi
158、opharma pipeline was strongest in China compared to other geographies,with 19%growth in the past year.The U.S.continues to represent nearly half of the emerging biopharma pipeline,although this share has declined slightly in recent years from a peak of 50%in 2016 to 46%in 2022.Europe and Japan repre
159、sent smaller shares of the emerging biopharma pipeline than they do the overall pipeline,with shares declining since 2012 as innovation has increased in China and South Korea.Europe and Japan saw declines of 5%and 20%,respectively,in the emerging biopharma pipeline over the last year.Exhibit 17:Numb
160、er of drugs and country share of emerging biopharma pipeline Phase I to regulatory submission based on company headquarter location,20072022Notes:Includes drugs with an active research program,with phase determined by the highest phase of research in each year regardless of indication.Company segmen
161、t when two or more companies are involved is determined by the larger sales segment.Each company involved in a drugs development is counted individually,so products with more than one company involved are counted more than once and may be included in more than one region.Europe is defined as any cou
162、ntry in continental Europe.R&D PIPELINEEmerging biopharma drug development is rising rapidly,particularly in China,whose share now exceeds that of EuropeSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.EuropeJapanChinaSouth KoreaU.S.All others200720007205001
163、,0001,5002,0002,5003,0003,5004,0004,5005,00044%48%49%46%24%24%22%17%3%2%4%5%9%20%3%4%4%6%0%10%20%30%40%50%60%iqviainstitute.org|23 Clinical trial activity was remarkably resilient even as the pandemic stretched through 2022,with a 2%decline in non-COVID trial activity over 2021,but a restoration of
164、pre-pandemic growth rates with an 8%increase over 2019.COVID-19 trials drove recent growth in infectious disease trials,with non-COVID-19 activity focused on a variety of other diseases.The total number of clinical trial subjects dropped to 1.8 million in 2022 due to a decline in COVID-19 enrollment
165、.The development of mRNA vaccines has accelerated in the last two years and expanded to multiple disease areas beyond COVID-19.Oncology trial starts reached historically high levels in 2022,up 22%from 2018 and primarily focused on rare cancer indications.Clinical trial starts in other important dise
166、ase areas returned to pre-pandemic level in 2022.Depression trial starts are 68%higher than pre-pandemic,with psychedelics being tested in nearly 25%of 2022 trial starts.Black/African American and Hispanic patient clinical trial representation has dropped over the past decade even as it varies widel
167、y across therapeutic areas.Clinical trial activityClinical trial activity was remarkably resilient even as the pandemic stretched through 2022,with a 2%decline in non-COVID trial activity over 2021,but a restoration of pre-pandemic growth rates with an 8%increase over 2019.24|Global Trends in R&D 20
168、23:Activity,Productivity,and Enablers Clinical trial activity was remarkably resilient even as the pandemic stretched through 2022,with a 2%decline in non-COVID trial activity over 2021,but a restoration of pre-pandemic growth rates with an 8%increase over 2019.COVID-19 trial starts accounted for 10
169、%and 6%of the total in 2021 and 2022 respectively.Planned non-COVID-19 Phase II and III trials declined by 2%from 2021,and Phase I declined by 1%while still exceeding pre-pandemic levels of trial starts.The double digit increases in planned trial starts in 2021 were related to 2020 trial delays driv
170、en by COVID-19 disruptions,and while activity has returned to a more normal trend,not all planned trials reported for 2021 will have started by the end of the year and,accordingly,trial start trends in recent years should be interpreted with caution.Exhibit 18:Total number of clinical trial starts b
171、y phase,20122022Notes:Phase II includes Phases I/II,II,IIa,IIb.Phase III includes Phase II/III and III.Terminated trials are included to track the activity still involved with their initiation,partial execution and termination.Trials were industry sponsored,interventional trials and device trials we
172、re excluded.CLINICAL TRIAL ACTIVITYTotal non-COVID-19 clinical trial starts decreased by 2%in 2022,while still 8%above the 2019 levelSource:Citeline Trialtrove,Jan 2023.735 586 369 Phase llPhase lllTotal all trials/Total excluding COVID-19 trialsCOVID-19Phase l1,2321,2691,5261,4031,4291,6011,7492,05
173、91,9552,1692,1621,5031,4181,5091,5971,6051,7791,8091,9211,7152,1852,1491,0401,0339961,0589419169771,0209101,1021,0763,775 3,720 4,031 4,058 3,977 4,298 4,538 5,008 4,5805,4565,3875,315 6,042 5,756 20000212022iqviainstitute.org|25 Infectious disease trials showed a di
174、p in non-COVID-19 starts in early 2020,concurrent with the appearance of the first COVID-19 trials.By mid-2020,a surge in trial starts had COVID-19-related trials nearly tripling those of infectious disease trial starts.New COVID-19 trials have dropped to less than half the level in 2020 as fewer ne
175、w targets have een identified.Overall,non-COVID-19 infectious disease trial activity has focused on therapeutics to a greater degree than vaccines.While there has been some overlap in the areas of focus,the relative priority for vaccines has remained on flu and pneumococcal trials,while therapeutics
176、 have focused on bacterial infections,HIV and hepatitis.Bacterial infections represent 21%of infectious disease trial starts in the last year,notable considering the continued lack of novel mechanisms and targets and the growing risks of antimicrobial resistance.Exhibit 19:Infectious disease clinica
177、l trial starts by diseaseNotes:Includes Phase I,Phase II(Phases I/II,II,IIa,IIb)and Phase III(Phase II/III and III).Terminated trials are included to track the activity still involved with their initiation,partial execution and termination.Trials were industry sponsored,interventional trials.CLINICA
178、L TRIAL ACTIVITYCOVID-19 trials drove recent growth in infectious disease trials,with non-COVID-19 activity focused on a variety of other diseasesSource:Citeline Trialtrove,IQVIA Institute,Jan 2023.Trial startsOther ID therapeuticsCOVID-19 therapeuticsCOVID-19 vaccinesOther ID vaccines02004006008001
179、,0001,2001,40020020201926%16%9%8%8%7%5%7%2%12%Other ID vaccines,2022,n=1477%1%3%13%29%21%7%19%Other ID therapeutics,2022,n=268 HIVViral hepatitisInfluenzaVector-borne diseasesHerpesPneumococcal diseaseRSVHPVUTIOtherBacterial infection26|Global Trends in R&D 2023:Activity,Productivity,and
180、Enablers The last four years have seen record-breaking numbers of subjects planned or enrolled in clinical trials,with the number approaching 4 million in 2021,and still an exceptional 1.9 million in 2022.The largest area of increase in study subjects has been infectious diseases,and even excluding
181、COVID-19 and Ebola,other infectious diseases had nearly 600,000 subjects in 2022 compared to 125,000 in 2018.In addition to the 1 million COVID-19 subjects in 2020,studies enrolled another 2.4 million in 2021 and more than 330,000 in 2022.Oncology trials accounted for 16%of the industrys clinical tr
182、ial subjects in 2022,with 289,000 subjects,down by 9,000 subjects but up from 8%of all trial subjects in 2021.As the COVID-19 vaccine trial surge recedes,the industry has an opportunity to keep the large set of recent trial subjects engaged for participation in ongoing and future clinical research.T
183、he number of subjects in trials is generally trending down as more trials focus on niche populations,although this has been reversed with some large population trials for infectious diseases,as well as cardiovascular and other metabolic trials(Exhibit 39).Exhibit 20:Clinical trial subjects,all phase
184、s,all diseases,20122022Notes:Subjects are the reported target or actual patients reported for trials with planned or actual start dates in each year.CLINICAL TRIAL ACTIVITYThe total number of clinical trial subjects dropped to 1.8 million in 2022 due to decline in COVID-19 enrollmentSource:Citeline
185、Trialtrove,IQVIA Institute,Jan 2023.EbolaOther infectious diseasesOncologyRare diseasesAll othersCOVID-190500,0001,000,0001,500,0002,000,0002,500,0003,000,0003,500,0004,000,0004,500,00020000212022iqviainstitute.org|27 Clinical testing of mRNA vaccines has dramaticall
186、y increased since 2016 with a more than 30-fold increase in the number of candidates by 2022.Starting in 2020,COVID-19 mRNA vaccines accounted for a significant portion of this growth and increased from 5 candidates beginning in 2020 to 26 in 2022.The increased focus on mRNA vaccines as a result of
187、COVID-19 vaccine development seems to have boosted other development with non-COVID-19 mRNA candidate development increasing 12-fold in the last five years.mRNA vaccine development for flu and respiratory infections was the highest non-COVID-19 segment in 2022,representing 35%of the development acti
188、vity.Despite making up the largest proportion of the pre-COVID-19 mRNA pipeline,oncology focused mRNA vaccines have not drastically increased and make up 8%of the pipeline in 2022.Exhibit 21:mRNA vaccine pipeline by therapy area,20162022Notes:Chart shows number of mRNA vaccine candidates under clini
189、cal development arranged based on the earliest trial start date.CLINICAL TRIAL ACTIVITYThe development of mRNA vaccines has accelerated in the last two years and expanded to multiple disease areasSource:IQVIA Institute,Jan 2023.Flu and respiratory infections(28)Oncology(27)Other infectious disease(1
190、5)Cardiometabolic(4)COVID-19(44)5538327303040506070200022Number of candidatesTrial initiationCytomegalovirus Epstein-BarrHerpes ZosterHerpes SimplexHIVMalariaNipahRabiesTuberculosisZika Total mRNA vaccine pipeline(118)28|Global Trends in R&D 2023:Activity,
191、Productivity,and Enablers Oncology and rare disease remain the two most active,though overlapping,therapeutic areas for trial starts in 2022,making up 40%and 33%of trial starts respectively in 2022.Though both areas have shown steady increases in trial starts for most of the past decade,rare disease
192、 and oncology rare both show a dip in 2022 as a function of their heavy overlap.Within oncology,rare disease starts have been variably up and down in the past four years,while non-rare oncology has been consistently growing-oncology non-rare represented 44%of the oncology trial starts in 2022,which
193、is the highest relative level in at least the past 10 years.The number of solid tumor trial starts has been growing steeply across the decade,although they remained stable in 2022;hematological trial starts have grown more slowly over the past 10 years.Predictive biomarker use has been increasing st
194、eadily over the past 10 years as well,and now includes at least three-quarters of the oncology pipeline,and much like the rest of the oncology pipeline,saw no growth in 2022.Exhibit 22:Clinical trial starts by year,20122022Notes:Phase II includes Phases I/II,II,IIa,IIb.Phase III includes Phase II/II
195、I and III.Terminated trials are included to track the activity still involved withtheir initiation,partial execution and termination.Trials were industry sponsored,interventional trials and device trials were excluded.Oncology has beensegmented into hematological or solid tumor in two charts,and int
196、o those with predictive biomarker and without biomarkers in two charts.Each pair ofcharts totals overall oncology.CLINICAL TRIAL ACTIVITYOncology trial starts remained at historically high levels in 2022,up 22%from 2018 and primarily focused on rare cancer indicationsSource:Citeline Trialtrove,IQVIA
197、 Institute,Jan 2023.Phase llPhase lllPhase l05001,0001,5002,0002,500205001,0001,5002,0002,50020000001220172022 2001220172022OncologyOncology non-rareOncology rareRare non-oncology HematologicalmalignanciesSolid tumorsOncolo
198、gy withpredictive biomarkerOncology withoutpredictive biomarkerRare diseasesiqviainstitute.org|29 Many of the key non-oncology therapeutic areas showed a very slight decrease in clinical trial starts in 2022 versus 2019,but in many cases,still remained above 2020 levels,suggesting a return to pre-pa
199、ndemic growth patterns.Exceptions to this include ophthalmology,infectious disease and womens health,where trial starts matched or slightly exceeded 2021 levels.Both NASH and respiratory show a slightly steeper decline,with respiratory continuing a decline started in 2020,and NASH total trial starts
200、 dropping by 37%between 2021 and 2022.Exhibit 23:Industry sponsored interventional trials by start date,20122022Notes:Phase II includes Phases I/II,II,IIa,IIb.Phase III includes Phase II/III and III.Terminated trials are included to track the activity still involved with theirinitiation,partial exec
201、ution and termination.Trials were industry sponsored,interventional trials and device trials were excluded.CLINICAL TRIAL ACTIVITYClinical trial starts in other important disease areas returned to pre-pandemic levels in 2022Source:Citeline Trialtrove,IQVIA Institute,Jan 2023.Phase llPhase lllPhase l
202、0204060800020406080100120140OphthalmologyWomens&sexual health007080GI/NASH00500600Infectious diseasesexcl COVID-19 00500600700800Immunology20500300350400Cardiovascular202004006008001000Dermatology20050
203、0Respiratory200500600700Metabolic/endocrinology 2000500600700800Neurology200000|Global Trends in R&D 2023:Activity,Productivity,and Enablers Overall depression trial starts have increased by 35%in the
204、past five years and have seen a particularly sharp rise since 2020.Major depressive disorder remains the most active segment,with more than 90%of 2022 trial starts.Activity around other key depression segments include minor increases in the last three years,but these still account for a small portio
205、n of the trial starts in 2022,with treatment resistant depression a focus in 23%,postpartum depression in 3%,and pediatric and adolescent depression in 3%of trial starts.In addition to top line segments,depression trials are focused on patients with a broad variety of co-morbidities and depression t
206、ypes(not shown).Notably,despite significant publicity,COVID-19 associated depression starts only accounted for 2%of the trial pipeline in 2022.As researchers and clinicians navigate a complex matrix of depression phenotypes across patients,the focus on mechanisms of action is becoming more targeted
207、and hypothesis-driven.2 Analysis of depression drug mechanisms of action paints a very complex picture with a variety of emerging novel mechanisms entering clinical testing,including novel serotonin reuptake inhibitors,neurotropic steroids,serotonergic psychedelics and NMDA psychedelics,which togeth
208、er account for 36%of the 2022 trial pipeline.Despite psychedelics now representing 24%of the trial starts in 2022,their potential role is evolving as sponsors and regulators will need to negotiate highly intensive regulatory and administration burden and unique uncertainties related to these control
209、led substances both in later stage clinical trials and in clinical practice.Exhibit 24:Depression clinical trials by segment and mechanism of actionNotes:Trials may focus on more than one segment and depression segment analysis includes some double counting as a result.Additionally,segment assignmen
210、t depends on reporting in the data source,and secondary depression segmentation may be under counted in the data set.CLINICAL TRIAL ACTIVITYDepression trial starts were 68%higher in 2022 than pre-pandemic with psychedelics being tested in nearly 25%of the 2022 trial startsSource:Citeline Trialtrove,
211、IQVIA Institute,Jan 2023.All depression00708090200212022Depression trial starts,20182022Major depressive disorderBipolar depressionTreatment resistant depressionPostpartum depressionPediatric and adolescent depression18%6%8%8%5%4%4%4%4%2%1%2%1%1%1%1%31%2022 depression trialmech
212、anisms of action n=84 Selective serotonin reuptake inhibitors(SSRI)Orexin receptor antagonistAtypical antipsychoticTypical antipsychoticCytokinesSerotonin and norepinephrine re-uptake inhibitors(SNRI)Neuroactive steroids(NASs)NMDA psychedelicSerotonin norepinephrine dopamine reuptake inhibitors(SNDR
213、I)Kappa-OpioidsNovel selective serotonin reuptake inhibitors(SSRI)Serotonergic psychedelicsOther/unidentified NMDA agonist/antagAMPA receptor agonistTRPC4 antagonistiqviainstitute.org|31 Despite increasing sponsor focus on diversity in clinical trials and diversity data reporting,and recent FDA guid
214、ance on diversity data reporting and clinical program diversity planning,Black/African American and Hispanic patient inclusion failed to reach U.S.demographic levels on average across interventional trials,including U.S.sites in the past decade.3,4,5 Black/African American participation has been dec
215、lining over the past decade,with an inclusiveness drop most notable in the past five years,with a 46%decline in U.S.Census indexed inclusion between 2018 and 2022 from 81%of US demographics to 43%.Hispanic inclusiveness has varied over the past decade and does not show as distinct a decline as Black
216、/African American inclusion,but also never reached U.S.demographic levels in the past decade.Hispanic patients were enrolled in trials at 53%of U.S.demographic levels in 2022.Black/African American and Hispanic patients are critically under-represented in trials using U.S.clinical sites and seeking
217、U.S.regulatory approval and are indicative of broader clinical development diversity opportunities to address ongoing healthcare disparities and expected ongoing regulatory and legislative requirements.3,4,5Exhibit 25:Phase II and III racial and ethnic inclusion indexed to U.S.demographics Notes:Inc
218、ludes all interventional Phase II and III trials with industry involvement and any U.S.sites listed on ClinicalTrials.gov starting after 2009 andcompleting between the start of 2012 and the end of 2022.Only trials with racial or ethnic data collected were included in calculation of Black/African Ame
219、rican or Hispanic patient inclusion,respectively.Analysis includes 4,947 trials over the time period.US average Black/African American representation is 13.6%and Hispanic representation is 18.9%.CLINICAL TRIAL ACTIVITYBlack/African American and Hispanic patient clinical trial representation dropped
220、over the past decadeSource:ClinicalTrials.gov,Dec 2022;U.S.Census Bureau QuickFacts,accessed Jan 2023;IQVIA Institute,Jan 2023.HispanicBlack/African American2020 U.S.demographics=100 007080902000202021202232|Global Trends in R&D 2023:Activity,Productivity,
221、and Enablers While Black/African American and Hispanic inclusion varied across therapeutic areas,both were higher across all therapeutic areas in trials which were recruited exclusively in the U.S.,and both saw lowest levels of inclusion in oncology.Specifically,Black/African American inclusion in t
222、herapeutic and geographic subsets ranged from 34%(2.5 times higher than U.S.demographic)of patients in U.S.-site-only psychiatry trials run between 2020 and 2022 to 3%(20%of the U.S.demographic levels)of globally run oncology trials in the same time period.Similarly,Hispanic inclusion ranged from 44
223、%(2.3 times higher than the U.S.Hispanic demographic)in U.S.run hepatology studies to 6%(31%of U.S.demographic)of globally run oncology trials.Notably,even in U.S.-site-only trials,Black/African American and Hispanic inclusion in oncology only reached 51%and 35%of the U.S.demographic levels respecti
224、vely.Given the significant proportion of the industry trial pipeline made up by oncology,averaging 38%over the past five years,the impact of poor inclusivity in oncology trials is driving the industry average inclusivity down across the timeframe.The dramatic inclusivity disparities in the largest c
225、linical development segment mirrors some of the starkest healthcare disparities in the U.S.and provides directed improvement opportunities that can impact the entire pipeline and healthcare outcomes at large.6,7Exhibit 26:Phase II and III Black/African American and Hispanic patient inclusion by ther
226、apeutic area and geography,20202022Notes:Includes all interventional Phase II and III trials with industry involvement and any U.S.sites listed on ClinicalTrials.gov starting after 2009 andcompleting between the start of 2020 and the end of 2022.Only trials with racial or ethnic data collected were
227、included in calculation of Black/African American or Hispanic patient inclusion,respectively.CLINICAL TRIAL ACTIVITYBlack/African American and Hispanic clinical trial participation varies widely across therapeutic areas in U.S.vs.global trialsSource:ClinicalTrials.gov,Dec 2022;U.S.Census Bureau Quic
228、kFacts,accessed Jan 2023;IQVIA Institute,Jan 2023.U.S.onlyGlobalU.S.onlyGlobal0%5%10%15%20%25%30%35%40%Hispanic inclusion in Phase II and IIIclinical trials by therapy area and geography 0%5%10%15%20%25%30%35%40%PsychiatryHematologyInfectious diseaseAllergy/Immunology/RheumatologyAllergy/Immunology/
229、RheumatologyCardiovascularNeurologyRespiratoryEndocrinologyHepatologyOncologyPercent of trial participantsBlack/African American inclusion in Phase II and IIIclinical trials by therapy area and geography 13.6%in2020 U.S.census 18.9%in2020 U.S.census HematologyInfectious diseaseRespiratoryHepatologyE
230、ndocrinologyNeurologyPsychiatryCardiovascularOncologyiqviainstitute.org|33 A total 64 novel active substances(NASs)launched globally in 2022,a decline from the more than 80 launched in each of the prior two years but representing a return to pre-COVID-19 levels of NAS launches.Declines in global NAS
231、 launches in 2022 were driven by fewer COVID-19 vaccines and therapeutics as the pandemics effects on society lessened,there were fewer U.S.accelerated approvals,and fewer NASs were launched only in China.A growing share of new launches in 2022 were first-in-class,reflecting the increasing availabil
232、ity of novel science for patients.Additionally,new launches are increasingly specialty products due to the growing number of complex molecules launched that often require advanced distribution and management systems to deliver them to patients.Since the first next-generation biotherapeutic launched
233、in 1998,42 next-generation biotherapeutics including cell,gene and RNA therapies have launched globally,with 19 occurring in the last three years and six of the 39 U.S.NAS launches in 2022,including two cell therapies,two gene therapies,and two RNAi therapies.Emerging biopharma companies originated
234、67%of all new drugs in 2022 and launched 69%of those,indicating more independence on the part of EBP companies in taking products from innovation to market.A total of 353 novel active substances have launched globally in the past five years,bringing the 20-year total to 903,with variations in timing
235、 of launch and access to these medicines across major geographies.New drug approvals and launchesThe number of global novel actives substances launched dropped by nearly a third in 2022 but still exceeded all pre-COVID-19 years and included a higher percentage of first-in-class drugs driving increas
236、ed availability of novel science for patients.34|Global Trends in R&D 2023:Activity,Productivity,and Enablers A total 64 novel active substances(NASs)launched globally in 2022,a decline from the more than 80 launched in each of the prior two years but representing a return to pre-COVID-19 levels.Onc
237、ology,neurology,and immunology have had rising shares of new launches in the past five years,with 173 of the 353 launches(49%)compared to 95 of 232(41%)from 2013 to 2017.Infectious diseases,including COVID-19 as well as anti-bacterial,anti-viral,anti-fungal and anti-parasitic treatments,have include
238、d novel treatments for HIV,Ebola,and more recently monkeypox,and are 16%of NAS launches over the last decade,with some year-to-year variability.The total 184 oncology launches in the past decade include some of the most groundbreaking new treatments in immuno-oncology as well as next-generation biot
239、herapeutics,and many treatments for rare cancers.Neurology includes 58 drugs in 10 years,and many of the more recent launches are for rare neuromuscular diseases as well as the new CGRP mechanism for migraine treatment,the first new mechanism for migraines in decades.The first next-generation biothe
240、rapeutic,an antisense oligonucleotide to treat cytomegalovirus retinitis,was launched globally in 1998.Since then,42 next-generation biotherapeutics including cell,gene and RNA therapies have launched globally,with 19 occurring in the last three years.Exhibit 27:Global launches of novel active subst
241、ances(NAS)by therapy area,20132022Notes:A novel active substance(NAS)is a new molecular or biologic entity or combination where at least one element is new.Includes NASs launched anywhere in the world by year of first global launch.Launch is determined using IQVIA audits of sales activity as well as
242、 companies public statements.Oncology includes supportive care&diagnostics.COVID-19 includes novel medicines only,and does not include previously approved medicines with new approved uses for COVID-19.NEW DRUG APPROVALS AND LAUNCHESA total of 64 novel active substances(NASs)were launched globally in
243、 2022Source:IQVIA Institute,Jan 2023.Respiratory(12)Dermatologics(18)Antidiabetics(24)Neurology(58)Infectious diseases inc.vaccines(73)COVID-19(20)Immunology(26)Oncology(184)Cardiovascular(24)All others(146)485449364007080902000212022Global NAS
244、launches 20132022Total(585)iqviainstitute.org|35 The 64 NASs launched globally in 2022 was a significant drop from the 93 launched globally in 2021,which was a record year and included a variety of unique launches.A small drop in the number of NASs can be attributed to a decline in the number of nov
245、el COVID-19 therapeutics and vaccines,a result of the declining impact of the pandemic on society and a shift away from COVID-19 pharmaceutical development.Across applications for new drugs and biologics and supplemental applications,the U.S.Food and Drug Administration approved 25 through accelerat
246、ed approvals in 2021 and dropped to less than half that in 2022.Of the global NAS launches between 2021 and 2022,a decline of 8 can be attributed to fewer U.S.accelerated approvals which represents a return to 2019 levels.China has seen an increasing number of NASs launched only domestically and not
247、 in other major markets.The number of NASs launched in China only had remained low in previous years(56)but increased to a peak of 21 in 2021 and fell back to 10 in 2022,more consistent with historic levels.Exhibit 28:Global launches of novel active substances(NASs)by characteristic,20212022Notes:Se
248、gmentations are non-overlapping and all COVID-19 NAS are grouped regardless of other characteristics.China only NAS are those only launched in China and not in other major markets.NEW DRUG APPROVALS AND LAUNCHESGlobal NAS launches declined in 2022,driven by declines in COVID-19,China only,and U.S.ac
249、celerated approval launchesSource:IQVIA Institute,Jan 2023.COVID-19U.S.accelerated approvalChina onlyAll others5043240070809036|Global Trends in R&D 2023:Activity,Productivity,and Enablers Over the past five years,a significant number of first-in-class medicines have
250、 become available,rising to 62%of those launched in 2022 and averaging 46%for the last five years.Over the past five years,143 drugs launched with orphan drug designations,representing 53%of the 268 launches,indicating a significant focus of innovative medicines for rare diseases.Specialty medicines
251、 those which treat chronic,complex or rare diseases and which also have complex treatment,distribution or patient management aspects,along with often high costs,made up 85%of the launches in the U.S.in 2022 with only six of the 39 2022 launches being traditional medicines.Unsurprisingly,this increas
252、e in specialty medicines in 2022 coincides with an increase in NAS that are biologics(59%)and a decrease in those that are oral administered(31%),as biologic medications and those provided by injection or infusion frequently result in more complex distribution and patient management as well as highe
253、r costs.As new medicines have increasingly targeted areas of high unmet need,clinical trial designs have used single-arm and open label designs,common in areas where it is less feasible or practical to conduct a more traditional randomized placebo-controlled trial.Open-label trials were used in the
254、approval trials for 43%of launches over the past five years.Exhibit 29:U.S.novel active substances(NASs)by product attributes and characteristics of clinical trials used for approval,20182022Notes:Includes NASs launched in the United States 20182022 regardless of the timing of FDA approval.Orphans i
255、nclude drugs with one or more orphan indications approved by the FDA at product launch.Products are not reclassified as orphan if they subsequently receive an approval for an orphan designated indication.First-in-class is based on FDA classification.Predictive biomarkers and companion diagnostics ba
256、sed on FDA approval information.Open label and single arm are clinical trial attributes determined based on the trial designs of trials noted by FDA as being relevant for the approval.NEW DRUG APPROVALS AND LAUNCHESMore than 60%of new launches in 2022 were first-in-class and more than half were biol
257、ogic,up from 35%five years agoSource:IQVIA Institute,Jan 2023.Companion diagnostic at approvalPredictive biomarker2000202022200000001820202022OralBiologicSpecialtyOrpha
258、nFirst-in-classBiomarkers&diagnosticsOpen labelSingle arm0%20%40%60%80%100%0%20%40%60%80%100%iqviainstitute.org|37Exhibit 30:Novel active substances(NASs)launched in 2022 in the United StatesNotes:Includes NASs launched in the U.S.in 2022.Oncology includes supportive care&diagnostics.Information col
259、lated from FDA and company releases and relevant clinical trial information.First-in-class based on FDA categorization.Any form of expedited review includes priority review,accelerated approval,breakthrough designation,or fast track determined by the FDA.If the time between the first patent filing(o
260、r start of the first clinical trial)and launch in the U.S.is less than or equal to five years this has been noted.NEW DRUG APPROVALS AND LAUNCHESNovel active substances(NASs)launched in 2022 included 33 specialty drugs and 26 EBP originatedSource:IQVIA Institute,Jan 2023.*ATTRIBUTES KEY:q=Oral,w=Bio
261、logic,e=Specialty,r=Next-gen biotherapeutic,t=Orphan,y=First-in-class,u=Expedited review,i=U.S Patent to launch 5 years o=EBP originated,1)=EBP launched THERAPY AREAINDICATIONMOLECULEBRANDATTRIBUTES*123456789 10OncologyAcute myeloid leukemiaolutasidenibRezlidhiaFR positive,platinum-resistant epithel
262、ial ovarian,fallopian tube,or primary peritoneal cancermirvetuximab soravtansineElahereHepatocellular carcinomatremelimumabImjudoMyelofibrosispacritinibVonjoNeutropeniaeflapegrastimRolvedonNon-small cell lung cancer(NSCLC)adagrasibKrazatiProstate-specific membrane antigen(PSMA)-positive metastatic c
263、astration-resistant prostate cancer(mCRPC)lutetium(177lu)vipivotide tetraxetanPluvictoRelapsed or refractory multiple myelomaciltacabtagene autoleucelCarvyktiteclistamabTecvayliUnresectable or metastatic melanomanivolumab+relatlimabOpdualagUnresectable or metastatic uveal melanomatebentafuspKimmtrak
264、NeurologyAmyotrophic lateral sclerosis(ALS)sodium phenylbutyrate+taurursodiolRelyvrioCerebral adrenoleukodystrophyelivaldogene autotemcelSkysonaCyclin-dependent kinase-like 5(CDKL5)deficiency disorder(CDD)ganaxoloneZtalmyInsomniadaridorexantQuviviqMyasthenia gravisefgartigimod alfaVyvgartPolyneuropa
265、thy of hereditary transthyretin-mediated amyloidosisvutrisiran AmvuttraImmunologyAtopic dermatitisabrocitinibCibinqotralokinumabAdbryPlaque psoriasisdeucravacitinibSotyktuPustular psoriasisspesolimabSpevigoSevere asthmatezepelumabTezspireHemat-ologyHemolytic anemiamitapivatPyrukyndHemophilia Betrana
266、cogene dezaparvovecHemgenixCold agglutinin diseasesutimlimabEnjaymo-thalassemiabetibeglogene autotemcelZyntegloInfectious diseasesCOVID-19bebtelovimabDengue feverdengue tetravalent vaccineDengvaxiaRecurrent vulvovaginal candidiasis(RVVC)oteseconazoleVivjoaAnti diabeticStage 3 and Stage 2 type 1 diab
267、etesteplizumabTzieldType 2 diabetes mellitustirzepatideMounjaroCardio vascularHeterozygous familial hypercholesterolemia(HeFH)or atherosclerotic cardiovascular disease(ASCVD)inclisiranLeqvioSymptomatic obstructive hypertrophic cardiomyopathymavacamtenCamzyosDerma-tologyPlaque psoriasistapinarofVtama
268、Pruritus associated with chronic kidney diseasedifelikefalinKorsuvaOthersAcid sphingomyelinase deficiencyolipudase alfaXenpozymeDetection and visualization of lesions with abnormal vascularitygadopiclenolEluciremIrritable bowel syndrome with constipation(IBS-C)tenapanorIbsrelaNeovascular age-related
269、 macular degeneration(nAMD)or diabetic macular edemafaricimabVabysmoTotals12 23 33621 24 30426 19 38|Global Trends in R&D 2023:Activity,Productivity,and EnablersNotes:NAS Launches in the U.S.have been segmented by the originator,which is based on the company which filed the first patent.The segmenta
270、tion laidout in exhibit 1 is applied based on the revenue or R&D spend at the time of the patent filing.Launch company segmentation has been assessed by theFDA filing company,further verified by the status of that company in relation to acquisitions by other companies as often filing company does no
271、t changeretroactively to reflect new ownership.The number of novel active substances(NASs)originated by EBP companies that have launched has doubled in the last five years,with 26 NASs launched in 2022 that originated from an EBP company.Although the share of NASs launched that are EBP originated va
272、ries significantly from year-to-year,EBP companies have originated 62%of U.S.NAS launches over the past five years,up from 49%over the previous five years and indicating increased EBP innovation reaching the market.Products originated by EBPs are increasingly launched by an EBP company,indicating mo
273、re independence on the part of EBP companies in taking products from innovation to market.EBP companies launched 69%of their own products in 2022,with 18 EBP originated and launched NASs.This was the largest share of total NASs that were EBP originated and launched(46%)over the last decade(average=3
274、3%).Exhibit 31:Companies originating and filing FDA regulatory submissions for NASs and percent of launchesby NAS launch yearNEW DRUG APPROVALS AND LAUNCHESEmerging biopharma companies originated 67%of all new drugs in 2022 and launched 69%of them,reflecting rising independenceSource:IQVIA Institute
275、,Jan 2023.EBP originated and launchedNon-EBP originatedEBP originated and another company launchedEBP originated0%10%20%30%40%50%60%70%80%90%100%2013 2014 2015 2016 2017 2018 2019 2020 2021 20222013 2014 2015 2016 2017 2018 2019 2020 2021 2022%of EBP originated NAS007080Number of NASsiqvi
276、ainstitute.org|39Notes:Novel active substance(NASs)is defined as a medicine with at least one novel ingredient and is noted in the year it launches for the first time inthe relevant geography.Fixed-dose combinations are NASs if one of the ingredients is novel but are not if both are previously avail
277、able.Emergency UseAuthorizations(EUAs)are counted as NASs in the year the medicine became available to patients and no exclusion is applied for approval type.COVID-19vaccines are counted as NASs based on the technology used to create them,with those made by mRNA technology counted as one NAS,and tho
278、se made byeach of eight sub-types of COVID-19 vaccines considered one NAS each,five types have launched to date with three more in development.A total of 64 novel active substances have launched for the first time globally in 2022,bringing the five-year total to 353.Based on molecules in the late-st
279、age pipeline,over the next five years an average of 60 NASs are expected to launch annually,expanding the number of NASs launched globally by 300 in the next five years.U.S.launches totaled 39 in 2022,the fewest NAS launches in a single year in the U.S.since 2016,likely reflecting delayed impacts of
280、 the pandemic,however still totaling a high of 268 in the last five years.The four largest EU member countries(France,Germany,Italy,Spain)and the UK saw a similar number of NAS launches to the U.S.in 2022 at 38,below a record number in 2021 of 50 launches;however,the 192 over the past five years lag
281、s 76 behind the U.S.Japan had 31 NAS launches in 2022,the fifth consecutive year with 30 or more launches,and although launching sooner after global launch than earlier in the century,continuing to lag behind the U.S.and other major markets.Chinas 29 confirmed NAS launches brings the five-year total
282、 to 193,with numbers driven by regulatory acceleration mechanisms,such as policies to expedite development and review and reimbursement reforms,all supporting a growing domestic innovation ecosystem and encouraging earlier entry by multi-nationals.Exhibit 32:Number of novel active substances(NASs)la
283、unched globally and in selected countries,20032022NEW DRUG APPROVALS AND LAUNCHESA total of 353 novel active substances have launched globally in the past 5 years,bringing the 20-year total to 903Source:IQVIA Institute,Jan 2023.Total launched 20032022Global(903)U.S.(775)EU4+UK(620)China(572)Japan(57
284、4)050030035040020032007200820018202240|Global Trends in R&D 2023:Activity,Productivity,and Enablers A Clinical Development Productivity Index provides a composite metric of success rates,clinical trial complexity,and trial duration.Clinical development productivity increased dr
285、amatically in 2022 driven by a decrease in complexity.The composite success rate across all therapy areas fell to 6.3%in 2022 while Phase II and III success rates rose 26%.Across disease areas,2022s composite success rate was below the 10-year trend with the exception of vaccines.Probability of succ
286、ess varies considerably across diseases,with infectious diseases and dermatology highest.Clinical trial complexity declined in 2022,following a significant increase in 2021 due to large COVID-19 trials.The declining number of sites for rare diseases and oncology trials is a key driver of the decreas
287、e in overall pipeline complexity.Trial durations have increased slightly over the past decade and Phase III,in particular,has been a driver in recent years.Oncology and rare diseases trial durations have been declining in recent years,attenuating overarching trial duration increases.The composite Cl
288、inical Development Productivity Index saw an increase in 2022 after steadily declining since 2015.Clinical development productivity indices were highest for infectious diseases while oncology extends trend as lowest.Clinical development productivityThe composite Clinical Development Productivity Ind
289、ex saw an increase in 2022 after steadily declining since 2015.iqviainstitute.org|41 The productivity of the clinical development process can be considered as a measure of trial outputs(drugs,innovation,trial success,etc.),compared to a measure of trial inputs or resources dedicated to obtaining tho
290、se outputs(e.g.,aspects of trial complexity,duration,monetary investments,etc.).Such measures of success,complexity,and trial duration were selected for inclusion in the Productivity Index as described above.Increases in success will increase productivity overall as will decreases in complexity or d
291、uration.Conversely,decreases in success will drive down the Productivity Index,as do increases in complexity and duration.To obtain current-state measures of trial complexity(mean number of endpoints,sites,countries,patients,eligibility criteria)as well as data on trial duration,attributes were leve
292、raged from the Citeline Trialtrove clinical trial database.In order to determine the number of eligibility criteria and endpoints from the unstructured or semi-structured text in trial records,natural language processing was used to identify common formatting patterns employed by trial sponsors in d
293、etailing these features.Success metrics were calculated from IQVIA Pipeline Intelligence based on medicines progressing to a subsequent research phase or being discontinued,suspended,withdrawn,or becoming inactive for three or more years(see Methodology).Each metric in each phase for each disease is
294、 indexed to the equivalent 2010 value for all diseases.Indices are available for each phase or as an average across phases.An analysis of productivity was conducted across all trials started between 2010 and 2022,with details included for therapy areas:cardiovascular,dermatology,infectious diseases,
295、endocrinology,immunology,neurology,oncology,respiratory,vaccines(separately from infectious diseases),and rare diseases.CLINICAL DEVELOPMENT PRODUCTIVITYA Clinical Development Productivity Index provides a composite metric of success rates,clinical trial complexity,and trial durationExhibit 33:Clini
296、cal Development Productivity IndexSource:IQVIA Institute,Jan 2023.COMPLEXITYSUCCESSPRODUCTIVITYEFFORTNumber of subjectsSuccess rateTrial outputIQVIA ClinicalDevelopmentProductivityIndexTrial inputsDuration of trialEligibility criteriaTrial sites Endpoints Countriesx+ComplexityProductivity=SuccessCom
297、plexity x Duration42|Global Trends in R&D 2023:Activity,Productivity,and Enablers Clinical development productivity a composite metric of success rates,clinical trial complexity,and trial duration rebounded in 2022,reversing a 10-year downward trend.Trial complexity returned to the previous trend af
298、ter an outlier high in 2021,while overall success rates improved slightly.Trial success rates were consistent with the baseline,indexing up slightly from 2021 but well below the highs of the past 10 years.Trial complexity dropped sharply in 2022 after unusually high levels in 2021,which were driven
299、by larger numbers of study subjects.All other components of the complexity indices declined slightly in 2022.Trial durations have remained essentially flat from 2017,reflecting difficulties in recruiting patients for more rare diseases and longer follow-up periods after treatment,even as some trials
300、 have been exceptionally faster than historic norms.Exhibit 34:Clinical Development Productivity Index and elements of productivity indexed to 2010 valuesNotes:Success rates and durations are indexed to the mean value for all diseases in 2010 equal to 1.The five complexity metrics are indexed to all
301、 diseases in 2010 equal to 1,and then summed,equaling 5.CLINICAL DEVELOPMENT PRODUCTIVITYClinical development productivity increased dramatically in 2022 driven by a decrease in complexitySource:IQVIA Pipeline Intelligence,Dec 2022;Citeline Trialtrove,IQVIA Institute,Jan 2023.DurationComplexitySucce
302、ssrateProductivity2000002000222021412101.51.07.05.01.51.0Productivity=SuccessComplexity x Duration5.0 6.06.01.01.31.0 1.2 1.2 1.0 iqviainstitute.org|43 The composite success rate for the pipeline fell
303、to a 10-year low in 2022,but embedded an increase in Phase II and III rates,offsetting declines in Phase I and at regulatory submission.Phase II success rates increased from 35%to 41%in one year,returning to the level last seen in 2017.Phase III rates rose to 54%,still far below the 67%10-year pre-p
304、andemic average.The pandemic has continued to disrupt the trials which are completed,and some trials which were understood to have failed in recent years due to extended inactivity had actually been continuing and have now completed successfully,resulting in retroactive restatement of past years suc
305、cess rates.The overall composite success rate in last years report was 5.2%,compared to the restated 6.9%in the current analysis.Phase I success rates dropped to 39%,a low since 2010 and down 7%from the 2021 rate.Success rates for products filing for regulatory approval also reached a low level,drop
306、ping to 72%in 2022.Exhibit 35:R&D composite success rate and average phase success rates Phase I to filing,20102022Notes:Phase success rates are calculated as the percentage of products reaching a subsequent phase in the year out of the total of products with an outcome including those which are dis
307、continued,suspended or withdrawn as well as those which have been inactive for three years.The date three years after the last update determines which year the drug is considered to have gone inactive and become included in the denominator of the success rate,except when desk research has concluded
308、the drug is still in active research.Products research status is assessed in any geography globally.CLINICAL DEVELOPMENT PRODUCTIVITYThe composite success rate across all therapy areas fell to 6.3%in 2022 while Phase II and III success rates rose 26%Source:IQVIA Pipeline Intelligence,Dec 2022;IQVIA
309、Institute,Jan 2023.Phase II avg 39%Composite success avg 13.2%Phase I avg 56%Phase III avg 67%20102019 regulatory submission avg 89%20000021Phase success%=Composite success%=Phase I x Phase II x Phase III x Regulatory submissionsSuccess(drug reaches any hi
310、gher phase)Total of success and failure54%52%57%56%58%63%57%61%52%48%46%46%39%29%37%38%37%37%52%40%41%39%36%34%35%41%57%65%64%66%75%81%70%71%62%58%55%52%54%87%85%88%88%94%92%87%92%90%89%76%83%72%7.5%10.5%12.2%12.0%15.1%24.5%13.6%16.2%11.6%8.8%6.5%6.9%6.3%44|Global Trends in R&D 2023:Activity,Product
311、ivity,and Enablers 2022s composite success rate of 6.3%was lower than the 10-year trendline in neurology,oncology,respiratory and cardiovascular classes.While most disease areas worsened in 2022,almost all had prior years restated as research previously thought to have become inactive had new progre
312、ss or updated activity.While activity levels remained resilient during the pandemic,oncology and rare diseases the two largest segments of the R&D pipeline all saw substantial decreases in composite success rates in 2022,continuing a trend over recent years.Vaccines,which had seen declining success
313、from 2016 to 2019,saw significant increases in success except in Phase I in 2022,mostly driven by the success of COVID-19 vaccines.Infectious diseases composite success declined slightly in 2022,continuing below the trendline for the observed period,driven by falling Phase I and regulatory submissio
314、n successes.Exhibit 36:R&D phase and composite success rates by therapy area,20102022Notes:Phase success rates are calculated as the percentage of products reaching a subsequent phase in the year out of the total of products with an outcome including those which are discontinued,suspended or withdra
315、wn as well as those which have been inactive for three years.The date three years after the last update determines which year the drug is considered to have gone inactive and become included in the denominator of the success rate,except when desk research has concluded the drug is still in active re
316、search.CLINICAL DEVELOPMENT PRODUCTIVITYAcross disease areas,the 2022 composite success rate was below the 10-year trend except for vaccinesSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.100%80%60%40%20%0%2010 2012 2014 2016 2018 2020 2022 Rare diseasesImmunology100%80%60%40%20
317、%0%2010 2012 2014 2016 2018 2020 2022 2010 2012 2014 2016 2018 2020 2022 2010 2012 2014 2016 2018 2020 2022 2010 2012 2014 2016 2018 2020 2022 Infectious diseasesDermatologyOncologyRespiratoryVaccinesMetabolic/EndocrinologyNeurologyCardiovascularPhase IPhase IIPhase IIIRegulatory submissionComposite
318、 Phase I to regulatory submissioniqviainstitute.org|45 The drop in composite success rate in 2022 overlays a complex set of dynamics across therapeutic segments,which in 2021 ranged from 1%to 19%,and in 2022 showed a narrower range from 1%to 14%.Infectious diseases,dermatology,and non-oncology rare
319、diseases had the highest composite success rates in 2022,the same or slightly lower than their 2021 level.Oncology,the largest segment of the pipeline,is currently seeing composite success rates of 3%,with slight differences between rare cancers(3%)and non-rare cancers(4%).Rare diseases had a compos
320、ite success rate of 7%in 2022,down from 14%in the prior year,reflecting highly dynamic results in these types of drugs.Products for cardiovascular disease saw success in 2021 of 12%,more consistent with long-term trends with 2020 and 2022 both representing unusually low success rates.It remains to b
321、e seen whether these outlier periods will continue.Exhibit 37:R&D composite success rate by therapy area in 2021 and 2022Notes:Phase success rates are calculated as the percentage of products reaching a subsequent phase in the year out of the total of products with an outcome including those which a
322、re discontinued,suspended or withdrawn as well as those which have been inactive for three years.The date three years after the last update determines which year the drug is considered to have gone inactive and become included in the denominator of the success rate,except when desk research has conc
323、luded the drug is still in active research.CLINICAL DEVELOPMENT PRODUCTIVITYProbability of success varies considerably across diseases,with infectious diseases and dermatology highestSource:IQVIA Pipeline Intelligence,Dec 2022;IQVIA Institute,Jan 2023.19%13%13%8%8%14%5%7%1%6%6%4%12%14%13%10%10%8%7%6
324、%6%4%3%3%2%1%Infectious diseases Rare oncology ImmunologyRare diseases Rare non-oncology Dermatology Oncology Respiratory Vaccines All diseases Neurology Oncology non-rare Cardiovascular 2021 success rate2022 success rate20%18%16%14%12%10%8%6%4%2%0%46|Global Trends in R&D 2023:Activity,Productivity,
325、and Enablers Following a period of increasing complexity in the first half of the last decade,trial complexity jumped in 2021 to an index of 136 compared to 2010 before dropping back to 121 in 2022,while still exceeding prior years.The unusually high number of trial subjects in 2021,mainly in COVID-
326、19 trials,is the main driver of lower overall complexity in 2022.The drop in the number of sites and the number of countries across industry trials was another driver of the decline in 2022,with sites 2.5%below 2010 levels and countries returning to the baseline index of 100,and some of the reductio
327、n in these metrics driven by ongoing COVID-19 trial disruptions and the conflict in Ukraine.The number of subjects on average has increased dramatically since 2018,with the 2021 index of 212 and 2022 at 154,both as a result of large-scale COVID-19 vaccine trials.As the COVID-19 pandemic subsides,the
328、 number of clinical trial subjects is likely to return to pre-pandemic levels.These measures,while not definitive in determining the complexity of operating a trial,do provide a useful guide for the ongoing effort associated with trials.Exhibit 38:Elements of complexity indexed to 2010 values,all ph
329、ases 20102022Notes:Terminated and withdrawn trials were excluded from the analysis.Trials were industry sponsored and interventional.Diagnostics,behavioral therapies,supplements,devices,and medical procedures were excluded.Infectious diseases excludes vaccines.CLINICAL DEVELOPMENT PRODUCTIVITYClinic
330、al trial complexity declined in 2022,following a significant increase in 2021 due to large COVID-19 trialsSource:Citeline Trialtrove,IQVIA Institute,Jan 2023.SubjectsEligibility criteriaSitesEndpointsCountries2202000200002020222021All complexity
331、iqviainstitute.org|47 In line with decreases in overall complexity,most of the evaluated therapy areas showed a decline in 2022.Oncology trials,which are among the most complex using the index,saw a drop in complexity in 2022 to its lowest level since 2011.As with the pipeline in general,this drop i
332、s highly correlated with the drop in number of sites and countries,which began in 2015 but was amplified by the pandemic.The number of subjects did increase sharply in 2022,however,perhaps related to a shift away from rare cancers.Rare disease trials have been showing a steady decline in complexity
333、since 2015 due to a declining number of sites and subjects,indicating more focus on smaller patient populations with the exception of large Ebola trials started in 2019.Fewer sites for rare disease trials was a notable inflection in the last three years.In recent years,vaccine trials have become increasingly larger than other trials and vary considerably in the number of subjects by disease target