1、FEBRUARY202 4Global Trends in R&D 2024ACTIVITY,PRODUCTIVITY,AND ENABLERSBiomedical advances are transforming healthcare globally.The multi-stakeholder ecosystem that enables this progress has been buffeted by the global COVID-19 pandemic and is resetting and refocusing on future opportunities to adv

2、ance the understanding of human biology and disease,discover and develop new therapeutics,and provide evidence of the clinical value of these innovations for individual patients,populations,and health systems.By all of the traditional metrics,including funding levels,numbers of trial starts,drug lau

3、nches,R&D success rates,and many others,it is clear that industry and investors continue to see tremendous value in the vast array of ongoing research programs around the world.This report assesses the trends in new drug launches and the overall number of initiated clinical trials.It also profiles t

4、he state of R&D funding and the activity of companies of different types.The results of research are compared to the input effort in a Clinical Development Productivity Index.The notable acceleration and adaptability of the innovation ecosystem is examined in terms of several enablers of R&D product

5、ivity,including the relationship between shortening trial durations and the white space within clinical development timelines that have been reducing for some diseases and increasing for others.The research included in this report was undertaken independently by the IQVIA Institute for Human Data Sc

6、ience as a public service,without industry or government 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,Taskin Ahmed,Chris

7、Bamford,Vaibhav Bhalotia,Tanya Bhardwaj,Lucy Haggerty,Julia Kern,Bhagyashree Nawar,Urvashi Porwal,Tanushree Thakur,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,vis

8、it iqviainstitute.org.MURRAY AITKENExecutive Director IQVIA Institute for Human Data ScienceIntroductionGlobal Trends in R&D 2024:Activity,Productivity,and Enablers2024 IQVIA and its affiliates.All reproduction rights,quotations,broadcasting,publications reserved.No part of this publication may be r

9、eproduced or transmitted in any form or by any means,electronic or mechanical,including photocopy,recording,or any information storage and retrieval system,without express written consent of IQVIA and the IQVIA Institute.REFERENCING THIS REPORTPlease use this format when referencing content from thi

10、s report:Source:IQVIA Institute for Human Data Science.Global Trends in R&D 2024:Activity,Productivity,and Enablers.February 2024.Available from www.iqviainstitute.orgTable of ContentsOverview 2R&D funding 4Clinical trial activity 12New drug approvals and launches 29Clinical development productivity

11、 40Productivity enablers 58Notes on sources 73Methodologies 74 References 75About the authors 76About the Institute 78OverviewR&D FUNDING R&D funding levels have rebounded in 2023 after a steep decline from the peak seen in 2020-21.While the number of deals has fallen,high profile and high value dea

12、ls indicate robust interest from investors and innovators in the next generation of therapies.Biopharma funding levels rebounded to$72Bn in 2023,up from$61Bn in 2022,although still well below the levels in 2020-21.M&A activity jumped to$140Bn from$78Bn in 2022,while median deal value dipped for the

13、second year.The leading deal and M&A activity areas related to antibody drug conjugates accounted for 47%of disclosed M&A deals valued over$2Bn and 85%of large oncology deals.Deals involving China-based companies remained significant and AI deals more than doubled.R&D expenditure reported by large p

14、harma corporations totaled a record$161Bn in 2023,an increase of almost 50%since 2018,and historically high at 23.4%of net sales for those companies.CLINICAL TRIAL ACTIVITY Trial starts have slowed to below pre-pandemic levels,reflecting fewer COVID-19activity and shifting research priorities.Clinic

15、al trial starts declined 15%in 2023 compared to the prior year and were down 22%from 2021 which included the peak of COVID-19-related trial activity.The three main drivers accounting for the slowdown were fewer COVID-19 trial starts,fewer non-COVID-19 starts by larger companies,and fewer by emerging

16、 biopharma companies.Trial starts from China-headquartered companies have risen to 28%of trial starts,up from 3%a decade ago,and an increasing proportion of Chinese companies have had international trial starts contrasted with the domestic-only activity of most firms.The top four diseases in terms o

17、f trial starts oncology,immunology,metabolic/endocrinology,and neurology account for 79%of trial starts and declined less than other diseases.Rare disease trial activity remains high and slowed less than trials focused on larger populations.The disease focus of rare disease research is predominately

18、 in oncology while diseases with larger populations study a wider variety of diseases.Novel oncology mechanisms,especially cell and gene therapies,ADCs and multi-specific antibodies,have risen to 25%of oncology trials.Industry sponsored cell and gene therapy trials have more than tripled over the la

19、st decade while non-industry have grown 5%.CAR T-cell therapy clinical research is focused on oncology,while other diseases may benefit from other cell and gene modalities.Obesity clinical trials in 2023 were up 68%from 2022 and have nearly doubled when compared to five years ago,including 124 drugs

20、 in active development,40%of which are GIP/GLP glucagon receptor agonists and 46%of which have oral formulations in development.Neurology research is focused on Alzheimers,Parkinsons,and epilepsy,with a range of other often rare diseases.Depression trial starts were 25%lower in 2023 than pre-pandemi

21、c with psychedelics being tested in nearly 40%of the 2023 trial starts.Infectious disease trials slowed to below pre-pandemic levels from both COVID-19 trials and other infection targets,and a significant reduction in trials starts for antibacterials.NEW DRUG APPROVALS AND LAUNCHES A total of 69 nov

22、el active substances(NASs)were launched globally in 2023,up six from the prior year and representing a return to pre-COVID-19 trends.A total of 362 NASs have launched globally in the past five years,bringing the 20-year total to 942.An increasing gap exists between countries such as the U.S.,with 26

23、7 NAS launches in the past five years,and the EU4+UK with 182,and China,which becomes the second largest with 192.While the number of NAS launches in China is rising,an increasing number are not available in other countries,reflecting both a rising domestic industry and a mix of reduced barriers and

24、 rising incentives for multinational NAS launches.Global NAS launches excluding China-only NASs were 52 in 2023,up one from 2022.2|Global Trends in R&D 2024:Activity,Productivity,and EnablersIndustry-wide clinical development productivity rose primarily due to improved success rates,which rose from

25、historic lows to the highest level since 2018.Efforts to manage trial complexity and durations have had more mixed results.There is a rising gap in terms of the drugs launched in the U.S.and those available to patients in the largest European countries,with 113 drugs(42%)launched in the U.S.in the p

26、ast five years that are not in Europe,while there are only 11(6%)European launches not in the U.S.First-in-class NAS launches continue to emerge from research,including six first-in-class cell and gene therapies launched in 2023,along with firsts in menopause,neurology,and oncology.Emerging biopharm

27、a companies originated 56%of all new drugs in 2023 and launched 53%of them,less than in recent years but still more than the first half of the decade.CLINICAL DEVELOPMENT PRODUCTIVITY Industry-wide clinical development productivity rose primarily through better success rates,which rose from historic

28、 lows to the highest level since 2018.Clinical development productivity reached an index level of 17.4 against a baseline of 20 in 2010,and continuing a rebound from the low of 12.8 in 2020.Most of the productivity increase in 2023 was driven by an increase in success rates,which rose to 10.8%in 202

29、3,almost doubling from lows in 2022 of 5.9%.Composite success rates were lifted by increased rates in Phase I,Phase III and regulatory review,and varied across disease areas with significant increases in oncology and rare diseases.Clinical trial complexity increased in 2023,returning to levels seen

30、in 2020 but with variations among the five elements of complexity measured.The declining number of countries and sites for rare diseases and oncology trials was a key driver of the decrease in overall complexity.The average number of countries in trials has been declining,more markedly in Phase II a

31、nd III studies,and including a marked shift to single-country studies even in later phases and rationalization to fewer countries in multi-country studies.Emerging biopharma are running more single country trials than large pharma with China trials driving recent trends.Another key element of produc

32、tivity is duration,and trial durations have declined while the white space before starting a subsequent research phase has increased,resulting in overall increases in development timelines.Nineteen drugs were launched less than five years into their patent terms in the past four years,up from eight

33、in total in the six years from 2014 to 2019.Median overall development duration was two to four years faster when expedited regulatory pathways were used,and is generally shorter for biologics,orphan,and specialty drugs,an important feature as these pathways and drug types have increasing share of n

34、ew drug launches.PRODUCTIVITY ENABLERS Industry sponsors are responding to therapeutic and regulatory shifts and opportunities with a range of strategies and approaches designed to enhance or enable productivity.Regulatory agencies are generally undergoing positive changes across geographies,address

35、ing transparency,flexibility,harmonization,speed,and simplicity,but capacity constraints are delaying implementation of consistent approaches in some geographies.Large pharmaceutical companies generally run trials with more countries and sites,and their country utilization over the decade is evidenc

36、e of ongoing and evolving analytical focus to optimize clinical trial footprints.Declining inclusion of Black/African American and Hispanic patients in the U.S.and global clinical trials over the last three years reflects challenges of a shifting therapeutic and geographic footprint and ongoing need

37、 for integrated trial planning.Clinical program design strategies,including use of predictive biomarkers,real-world evidence,single-arm trials,and combined-phases,can contribute to shorter development durations.Novel trial designs have averaged 18%of trials since 2020,led by oncology,with more than

38、29%novel designs,and these studies can contribute to slower initial development but faster and greater overall program success.Decentralized methodologies remain a stable feature of trial activity,albeit at a lower level after the COVID-19 driven peak in 2020.Clinical development programs resulting

39、from AI utilization in discovery are maturing with an increased number of late-stage programs and examples of new indications for exiting drugs,but are still to deliver a novel active substance to the market.Industry has been focused on minimizing regulatory setbacks in the form of complete response

40、 letters(CRLs),especially for clinical reasons,although overall rates were higher in 2023.Operational or non-clinical reasons for CRLs have been impacting emerging biopharma companies differently than larger firms.iqviainstitute.org|34|Global Trends in R&D 2024:Activity,Productivity,and Enablers Bio

41、pharma funding levels rebounded to$72Bn in 2023,up from$61Bn in 2022,although still well below the levels in 2020/21.M&A activity has jumped to$140Bn from$78Bn in 2022 while median deal value dipped for the second year.Deals between pharma companies dropped by 14%from 2022 to 2023,mostly from deals

42、involving EBP companies.High profile deals involving Chinese companies included multiple antibody drug conjugates and both inward and outward deals.The leading deals in 2023 included 11 deals over$5Bn and focused on cancer,neurology and cardiovascular.There were six deals related to antibody drug co

43、njugates(ADCs)totaling$90Bn in deal value,representing 45%of the overall$200Bn related to the 31 deals valued above$2Bn each.More than$12Bn in life sciences deals with AI,machine learning,or advanced analytics were announced in 2023,more than double the level in the prior two years with the value pe

44、r deal jumping to$98Mn from an average of$27Mn in the prior three years.R&D expenditure by large pharma corporations totaled a record$161Bn in 2023,an increase of almost 50%since 2018 and historically high at 23.4%of companies net sales.R&D fundingR&D funding levels have rebounded in 2023 after a st

45、eep decline from the peak of the pandemic.While the number of deals has been falling,high profile and high value deals indicate robust interest from investors and innovators in the next generation of therapies.iqviainstitute.org|5 Biopharma funding,including IPOs,follow-on funding,and venture capita

46、l investment,rebounded in 2023 after a sharp slowdown in 2022 from the heightened levels during the pandemic.The level of activity still exceeds the 2019 level,although the mix of funding types has shifted,and IPO activity was notably lower.The shifts in deal activity reflect changes in the types of

47、 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 slowed in the most recent year.In 2023 alone,follow-on funding represented about 38%of biopharma funding,for which 91%was comprised of c

48、ompanies headquartered in the U.S.Companies headquartered in China and Europe have seen deals slow more dramatically than those in the U.S.,decreasing by 59%and 74%,respectively.Exhibit 1:Biopharma funding levels US$Bn,20142023Notes:IPO means initial public offering;Follow-on refers to a public offe

49、ring 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 investments.R&D FUNDINGBiopharma funding levels rebounded in 2023 despite fewer IPOsSource:BioWorld,Jan 2024.Follow-onsPublic/otherPrivateTot

50、alIPOs202320002020292224548906402225820406080100120140Values US$Bn 6|Global Trends in R&D 2024:Activity,Productivity,and Enablers M&A deal values rebounded to$140Bn in 2023 from a low in 2022 but have

51、not yet reached the levels seen in 2019 and 2020.Similarly,the number of M&A deals have slowly decreased since 2019,with an uptick to 136 deals in 2023.Although the median disclosed deal value in 2023 of$175Mn was 42%below the$301Mn in 2021,the aggregate deal value increased driven by some very high

52、 value deals.High profile M&A deals were led by Pfizer and Seagen for$43Bn focused on oncology antibody drug conjugates(ADCs).Another landmark M&A deal in 2023 was between AbbVie and Immunogen for$10.1Bn,which also led to the acquisition for a first-in-class antibody drug conjugate(ADC)in oncology.I

53、n the same year,BMS acquired RayzeBio for$4.1Bn(Exhibit 5).Deal value is the disclosed value of the deal when announced;for 2023 alone,the number of disclosed deals represent 65%of total M&A deals.For the past five years,the number of non-disclosed M&A deals represent 43%of total M&A deals,which if

54、valued at the median deal value in the year they occurred,would add$81Bn(14%)to the disclosed$743Bn for an estimated total value of$851Bn over five years(not shown).Exhibit 2:Biopharma M&A Activity US$Mn,20142023Notes:M&A is involving at least one biopharmaceutical company.Deal value is the disclose

55、d value of the deal when announced.R&D FUNDINGM&A activity has rebounded overall with deal value and deal counts rising,while median deal value dipped for the second yearSource:BioWorld,Jan 2024.479597589779200060050040030020060140120

56、00200Number of M&A dealsM&A value US$BnMedian value US$BnNumber of M&A deals202320002020214 2015 2016 2017 2018 2019 2020 2021 2022Disclosed deal dalue US$MnDisclosed deal value US$BnM&A value and numberMedian M&A Value and Number(with Disclosed

57、 details)Number of M&A dealsNumber of M&A dealsiqviainstitute.org|7 Emerging biopharma companies(EBPs)defined as those with less than$200Mn in R&D spending and less than$500Mn per year in annual revenue have expanded their involvement in deals steadily over the past five years,with a slight dip in 2

58、023.In 2019,large and-mid-sized companies those with more than$5Bn in global revenue were involved in 44%of deals that involved other large and mid-sized or emerging companies;while that share of the company deal activity has remained steady,as a level of deals of the company,it has dropped to 406.T

59、he shifts in activity over the past five years have meant that 74%of all deal activity between these types of companies involves an emerging company,even as the activity between emerging companies without a larger firm now represent 66%of deals.The rising independence of emerging biopharma companies

60、 in recent years started to shift in 2021 as the share of deals involving larger companies jumped from 30%in 2021 to 35%in 2023.Novel drugs developed by emerging biopharma are also being launched by them less than in recent years,with 53%of the 26 EBP-originated NAS launches in the U.S.in 2023 also

61、being launched by an EBP(Exhibit 31).Exhibit 3:Number and share of deals by company segment,20192023Notes:Deals in this analysis are excluding non-funding deals.Funding deals are deals that involve research grants or funding from govt institutions,govt bodies,universities or other academic instituti

62、ons.Excluding VC and Funding Grants from Non-Commercial.Excludes deals where one side is not a pharmaceutical company.Emerging biopharma(EBP)are defined as companies with$500Mn of prescription pharmaceutical sales and$2Bn in 2023 by therapeutic areaNotes:ADCs are defined as antibody drug conjugates.

63、Source:IQVIA Pharmadeals,Dec 2023.AcquisitionAlliance/collaborationN=31 deals$2Bn,Total$200BnOthers(9 deals/$39Bn)Cardio Metabolic(6 deals/$16.8Bn)Neurology(4 deals/$34Bn)Merck+Prometheus 10.8Roche+Telavant 7.3Astellas+Iveric 5.9Novartis+Chinook 3.5Proxygen+Merck&Co 2.6Bausch&Lomb+Novartis(asset acq

64、)2.5Lilly+DICE 2.4Quell+AstraZEneca 2.1Belharra+Genentech 2.1Pfizer+Seagen(ADCs)43.0Daiichi+Merck(ADCs)22.0AbbVie+Immunogen(ADCs)10.1Systimmune+BMS(ADCs)8.4BMS+Mirati 5.8BMS+Razebio 4.1Nurix+Seagen(ADCs)3.5C4+Merck&Co(ADCs)3.1AbbVie+Immunonome 2.8Nanobiotix+J&J 2.8Monte Rosa+Roche 2.1Orionis+Genente

65、ch 2.0Alnylam+Roche 3.1Roche+Carmot 3.1Sanofi+Provention Bio 2.9Valo Health+Novo Nrdisk 2.8Aspect Biosystems+Novo Nordisk 2.7Avidity Bioscience+BMS 2.3BMS+Karuna 14.0Abbvie+Cerevel 8.7Biogen+Reata 7.3Neurocrine+Voyager 4.455%17%8%20%Oncology(12 deals/$109.6Bn)R&D FUNDINGThe leading deals in 2023 inc

66、luded 11 deals over$5Bn and focused on cancer,neurology and cardiovascular10|Global Trends in R&D 2024:Activity,Productivity,and Enablers More than$12Bn in life sciences deals with AI,machine learning or advanced analytics were announced in 2023,more than double the level in the prior two years,with

67、 the value per deal jumping to$98Mn from an average$27Mn in the prior three years.In 2023 alone,the worth of deals is about nine times higher than what it was in 2019 and almost four times higher than what it was in 2022;there are likely many more deals,collaborations,or uses of technology which wer

68、e not disclosed.The largest deal disclosed in this area was between Exscientia and Sanofi to discover an artificial intelligence-driven drug for oncology and immunology for$5.2Mn;other deals include Moderna and Immatics for$1.8Mn for oncology therapeutics and Shape Therapeutics and Roche to develop

69、gene therapies for neurodegenerative diseases(Alzheimers,Parkinsons,dementia)for$3Mn.Oncology represents about 43%of AI deals in 2023 and a total of 35%of deals for the last five years.Advances in artificial intelligence(AI),machine learning,and other advanced analytics are increasingly being applie

70、d to the life sciences with deals announced focusing on drug discovery and patient cohort identification,among others.According to the FDA,in 2021,more than 100 drug and biologic application submissions used these technologies;this led to the release in May 2023 of an FDA paper for stakeholders to d

71、iscuss the use of AI/ML in drugs and biological products development.2Exhibit 6:Number and value of deals with artificial intelligence,machine learning,informatics,20192023Notes:The deals in this analysis include deals which referred to key search terms of artificial intelligence(AI),machine learnin

72、g,informatics or advanced analytics capabilities.Not all deals of this nature have been disclosed.Source:IQVIA Pharmadeals,Dec 2023.Deal value US$BnDeal value US$BnNumber of dealsNumber of deals25020002220230.93.05.95.312.8R&D FUNDINGOver$12Bn in life sciences deals

73、with AI,machine learning or advanced analytics were announced in 2023iqviainstitute.org|11 The largest pharmaceutical companies together spent more than$161Bn on research and development in 2023,up$53Bn or 49%from the level five years ago(2018).R&D spending rose to 23.4%in aggregate across these 15

74、companies,a sharp increase over 2022,due in part to lower sales by this cohort as COVID-19 vaccines and therapeutics sales declined,and the accounting for acquired R&D as an expense by some companies.R&D expenditure and sales are as reported in company financial statements.R&D expenses can include w

75、rite-offs of failed R&D programs developed internally or acquired,which can bring year-to-year variability in the level of total spending.These represent the total company view and some divisions,such as consumer health,are typically less R&D-intensive than the pharmaceutical division.Exhibit 7:Larg

76、e pharma R&D spending as a percentage of sales 20142023*,US$BnNotes:Based on financial reporting for twelve months ending Dec 31,2023 for all companies except Amgen,Astra Zeneca,Gilead,and Eli Lilly which are based on 12 months ending Sept 30,2023.All other years reflect total R&D for the calendar y

77、ear indicated.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 company view,and some divisions such as consumer health are typically less R&D-intensive

78、 than the pharmaceutical division.The total expenditure is as reported by companies in their financial statements.Source:Company financial statements,IQVIA Institute,Nov 2023.R&D spendingR&D spending as a percentage of sales2000202020119.3%19.6%

79、18.7%18.2%17.5%17.2%20.4%19.3%18.8%23.4%R&D FUNDINGR&D expenditure by large pharma corporations totaled a record$161Bn in 2023,an increase of almost 50%since 201812|Global Trends in R&D 2024:Activity,Productivity,and Enablers Clinical trial starts declined 15%in 2023 compared to the prior year and w

80、ere down 22%from 2021,which included the peak of COVID-19 related trial activity.Emerging biopharma companies started 416 fewer non-COVID-19 trials in 2023 than they did in 2021,while larger companies started 524 fewer.Trial starts from China-headquartered companies have risen to 28%of trial starts,

81、up from 3%a decade ago.In the past three years,more than one-quarter of Chinese companies have had international trial starts,up from 21%over the prior seven years.The top four diseases in terms of trial starts oncology,immunology,metabolic/endocrinology,and neurology account for 79%of trial starts

82、and declined less than other diseases.Rare disease trial activity remains high and slowed less than trials focused on larger populations;the disease focus of rare disease research is predominately focused in oncology,while diseases with larger populations study a wider variety of diseases.Novel onco

83、logy mechanisms,especially cell and gene therapies,ADCs and multi-specific antibodies have risen to 25%of oncology trials.Industry sponsored cell and gene therapy trials have more than tripled over the last decade,while non-industry have grown 5%.CAR T-cell therapy clinical research is focused on on

84、cology,while other diseases may benefit from other cell and gene modalities.Obesity clinical trials in 2023 were up 68%from 2022 and have nearly doubled when compared to five years ago,including 124 drugs in active development,40%of which are GIP/GLP glucagon receptor agonists and 46%of which have o

85、ral formulations in development.Neurology research is focused on Alzheimers,Parkinsons and epilepsy,with a range of other often rare diseases.Depression trial starts were 25%lower in 2023 than pre-pandemic,with psychedelics being tested in nearly 40%of the 2023 trial starts.Infectious disease trials

86、 slowed to below pre-pandemic levels from both COVID-19 trials and other infection targets,including a significant reduction in trials starts for antibacterials.Clinical trial activityTrial starts have slowed to below pre-pandemic levels with some of the decline explained by less COVID-19 activity,w

87、hile the remainder highlights shifting research priorities.iqviainstitute.org|13 Clinical trial starts slowed in 2023,with a 15%decline compared to 2022 and down 22%when compared to 2021,with 32%of the decline driven by COVID-19 trials,which have declined 69%compared to 2021(Exhibit 9).Without these

88、 COVID-19 trials,trial starts have slowed to below the pre-pandemic level.Phase I had the most declines,with 19%fewer than 2022;Phase II activity decreased by 11%and Phase III had a 15%decline in planned or actual trial starts,matching the overall trend.With COVID-19 trials no longer driving trends,

89、the reduction in starts is more driven by companies reduced study starts with multiple and interactive drivers,including companies from key geographies such as China,with patterns visible in emerging biopharma as well as larger company segments.While COVID-19 disruptions have largely faded,the impac

90、t of historic delays in starts or completions will have continuing effects on companies subsequent activities,especially for those who are more dependent on funding flows.It is notable that trial starts include both planned and actual starts,and not all planned trials reported here will have started

91、 by the end of the year 2023 and,accordingly,trial start trends in recent years should be interpreted with caution.Exhibit 8:Total number of clinical trial starts by phase,20142023Notes:Phase II includes Phases I/II,II,IIa,IIb.Phase III includes Phase II/III and III.Terminated trials are included to

92、 track the activity still involved with their initiation,partial execution and termination.Trials were industry sponsored,interventional trials and device trials were excluded.CLINICAL TRIAL ACTIVITYTotal clinical trial starts decreased by 15%in 2023,dipping below pre-pandemic level as COVID-19 tria

93、l starts slowedSource:Citeline Trialtrove,Jan 2024.1,5501,4371,4561,6411,7952,1561,1502,4162,3551,9001,5381,6181,6351,8611,8521,9752,1532,5012,2271,9721,0111,0829579521,0141,0681,1591,3331,1721,001Phase IIPhase ITotal all trialsPhase III2000202021202220235,1994,6614,4544,0484,1

94、374,0995,4626,2505,7544,87314|Global Trends in R&D 2024:Activity,Productivity,and Enablers Clinical trial starts declined 22%or 1,377 from 2021 to 2023,with three key drivers associated with COVID-19,emerging biopharma and larger companies.Emerging biopharma companies have had an overall larger impa

95、ct on the slowdown as they had started more COVID-19 trials than larger companies,and their COVID-19 decline(289)was greater than the reduction by larger companies(148).EBP COVID-19 trial starts were down 66%to 152 in 2023,whereas larger companies are down 80%and started only 37 trials in this area

96、in 2023.Emerging companies non-COVID-19 trials were down 416 or 13%,with most of the decline in earlier phases.Outside COVID-19,larger companies had a larger decline,reflecting 524 or 22%fewer trial starts in 2023 than in 2021,the same as the overall market decline.Over half of the decline in trial

97、starts sponsored by larger companies are associated with a decrease in multi-study clinical programs,particularly on molecules which first entered the clinic more than 10 years ago.Larger companies are also licensing assets later,or not at all,to manage investment risk,as seen with the larger number

98、 of EBP originated launches without a larger-company partner(Exhibit 31).Exhibit 9:Change in industry interventional trials between 2021 and 2023Notes:Industry interventional studies phases I,II,III.Company segment when two or more companies are involved is determined by the larger sales segment.Lar

99、ger and EBP segments exclude COVID-19.Larger companies includes segments large,mid and small.Large companies are those with with global prescription sales exceeding$10 billion in the calendar year.Mid-size companies have global prescription sales between$5 and$10 billion in the calendar year.Small c

100、ompanies have global prescription sales between$500 million to$5 billion in the calendar year.Emerging biopharma(EBP)companies are defined as those with either R&D spend$200 million or prescription sales up to$500 million.Multi-study clinical programs defined as 10 or more studies for the primary te

101、sted drug since 2000.CLINICAL TRIAL ACTIVITYTrial starts declined 22%since 2021 impacting emerging biopharma more than larger companiesSource:Citeline Trialtrove,Jan 2024.Phase IIPhase ITrialsCOVID-19Phase III2023Larger companiesEBPCOVID-192021-524-22%-416-13%-437-69%6,2504,873Overall trials:-22%iqv

102、iainstitute.org|15 The contribution of emerging biopharma companies those with less than$500Mn in annual sales and R&D spending less than$200Mn per year remains the largest,while large pharma companies those with greater than$10Bn in annual sales represent a smaller share of the trial activity.Large

103、 pharma companies now represent 27%of trial starts,up 3%from 2022 but down from 50%in 2014.Mid-sized and small companies,with revenues between$500Mn and$10Bn in annual sales,represent 11.3%,down from 12.9%in 2022 and 13%from 2014.EBP companies sponsored 66%of Phase I trial starts in 2023,nearly thre

104、e times the 23%from large companies.In Phase II,EBP started 62%of studies compared to the 54%of Phase III they sponsored;in 2014,EBP companies were a smaller share of starts with 44%of Phase II and 27%of Phase III.Large companies started 27%in Phase II in 2023 and 33%in Phase III,both down from 48%a

105、nd 54%,respectively,in 2014.Emerging biopharma companies have increased their share of early phase trials in the past decade;while the historic pattern for research assets to be acquired or licensed by larger companies persists,it appears that the acquisitions were happening at earlier development p

106、hases a decade ago than today.Exhibit 10:Share of clinical trial starts by phase and company segment,20142023Notes:Industry interventional studies phases I,II,III.Company segment when two or more companies are involved is determined by the larger sales segment.Large companies are those with global p

107、rescription sales exceeding$10 billion in the calendar year.Mid-size companies have global prescription sales between$5 and$10 billion in the calendar year.Small companies have global prescription sales between$500 million to$5 billion in the calendar year.Emerging biopharma(EBP)companies are define

108、d as those with either R&D spend$200 million or prescription sales up to$500 million.CLINICAL TRIAL ACTIVITYEmerging biopharma companies are responsible for two-thirds of trial starts,but declined the most since the peak in 2021Source:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.3,0002,5002

109、,0001,5001,0005000MidSmallEBPLarge2000202021202220233,0002,5002,0001,5001,00050002000202021202220231,4001,2001,0008006004002000200020202120222023Phase IPhase IIPhase III16|Global Trends in R&D 2024:Activity,Productivity,and Enablers T

110、rial starts are sponsored by companies from across major geographies,with 2,357 companies sponsoring trial starts in 2023,up from 993 in 2008 and reflecting a halving in the average number of trials per company from four in 2008 to two in 2023(data not shown).The rising participation of companies he

111、adquartered in China is the most dramatic change over the period,with their share of starts rising to 28%from 3%in 2013 and 1%in 2008.The share of starts from companies headquartered in Europe has declined from 38%in 2013 to 23%in 2023,and these companies now start about two-thirds as many trials as

112、 U.S.headquartered companies,whereas in 2013 and earlier years,European HQ companies started more trials than U.S.companies.Japanese companies share of trial starts has declined to 4%from 11%in 2013 and are consistent with the decline in starts from 501 to 244 over the same period.South Korea is hom

113、e to a dynamic group of companies including generics and biosimilars,and as their share of trial starts has risen,it reflects the increasing importance of the multiple niches these companies occupy.Exhibit 11:Number of Phase I to III trial starts based on company headquarters location,20082023Notes:

114、Includes interventional,industry sponsored trials which are in Phase I to Phase III.Each company involved in a trial is counted individually,so products with more than one company involved are counted more than once and trials may be included in more than one region to reflect their sponsors headqua

115、rter geography.Europe is defined as any country in continental Europe.Trial sponsors are subject to variations in company naming and industry consolidation may result in multiple companies being counted individually when they are part of a larger corporate parent.CLINICAL TRIAL ACTIVITYTrial starts

116、from China-headquartered companies have risen to 28%of trial starts from 3%a decade agoSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.8,0007,0006,0005,0004,0003,0002,0001,000050%45%40%35%30%25%20%15%10%5%0%U.S.EuropeJapanChinaSouth KoreaAll others20232008200082013201837%38%3

117、3%34%38%29%22%23%11%8%5%4%3%14%27%28%4%4%4%4%iqviainstitute.org|17 For industry interventional trials,sponsors with a Chinese headquarters started 657 trials in 2023,down from 800 in 2022,but a consistently high number indicates the growing activity of these companies.Most Chinese companies have onl

118、y had trial starts with sites in China,while 27%of the companies have included non-China sites in trials theyre involved with(which may include non-Chinese partners).Domestic-only companies have between one and two trial starts per company per year,whereas those companies with some international act

119、ivity have averaged four to five trials per company,suggesting this international aspect is related to the growth and maturation of these firms.Chinese companies have a greater focus on earlier phases in their trials than the industry overall,as trials with sites in China are a leading location for

120、these early phase studies globally(Exhibits 42,52).China HQ companies accounted for 28%of trial starts in 2023(Exhibit 11)but have a higher percentage of trial starts in oncology and COVID-19,illustrating the relatively higher focus those diseases have in these companies priorities.Exhibit 12:Indust

121、ry interventional trials Phase I to IIINotes:Includes interventional,industry sponsored trials which are in Phase I to Phase III.Chinese headquartered companies have been analyzed for the countries included in trials they started each year,and the company has been assigned to a segment based on whet

122、her those trials included international countries in any of the trials they started.Not all of a companys trials are China-only or including non-China sties.Disease and therapy areas for trials are mutually exclusive.CLINICAL TRIAL ACTIVITYOver one quarter of Chinese companies are active internation

123、ally;Chinese firms are focused on oncology and COVID-19Source:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.2542445894472373504685544457567275780065738%24%24%17%20%28%41%21%17%China share all trials:28%8007006005004003002001000OncologyImmunologyMet

124、abolic/EndocrinologyNeurologyCardiovascularInfectious diseasesCOVID-19Vaccine infectiousdiseasesAll othersStarts only in ChinaGrand totalStarts including non-China countries20232014 2015 2016 2017 2018 2019 2020 2021 20220%10%20%30%40%50%Number of Chinese HQ companies by trial footprintChina HQ comp

125、any share of trials18|Global Trends in R&D 2024:Activity,Productivity,and Enablers Trial starts declined 15%in 2023 with 4,873 trials started or planned to be started from Phase I to Phase III,reflecting a 52%reduction in COVID-19 trial starts since 2022 and slower declines in all other therapy area

126、s.Oncology remains the focus of the pipeline,comprising 44%or 2,143 trials and down 3%since 2022.Immunology trials accounted for 14%of starts in 2023 and were down 7%.Neurology represented 10%of trials,down 26%in 2023 and including a mix of rare diseases as well as larger population research targets

127、.Cardiovascular trials were 5%of trial activity and down 7%in 2023,slowing less than all therapies except oncology and immunology.Vaccines for infectious diseases saw 131 trial starts,down 14%,and infectious disease research excluding vaccines or COVID-19 declined 34%in the past year,potentially res

128、ulting from above normal starts in prior years.Exhibit 13:Clinical trial starts by therapeutic area,Phases I to III,20142023Notes:Includes drugs with an active research program,with phase determined by the highest phase of research regardless of indication.Includes industry sponsored,interventional

129、trials.Endocrinology includes diabetes,other endocrinology and GI/NASH.All others includes(womens health,other genitourinary excluding womens health,respiratory,hematology,and all others).Immunology includes autoimmune and inflammation.Oncology includes both solid-oncology and hematology oncology.Ne

130、urology is mental health and other CNS.Vaccines are infectious disease vaccines(i.e.,cancer vaccines are not included).Infectious diseases are not including vaccines or COVID-19.COVID-19 include any trials which mention COVID-19 and could include repurposing of existing therapeutics.CLINICAL TRIAL A

131、CTIVITYThe top 4 diseases account for 79%of trial starts and declined less than other diseasesSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.7,0006,0005,0004,0003,0002,0001,0000Infectious diseasesVaccine infectious diseasesCOVID-19OncologyImmunologyNeurologyCardiovascularNetabolic/Endo

132、crinologyAll others202320002020212022iqviainstitute.org|19 The top four disease areas for trial starts oncology,immunology,metabolic/endocrinology,and neurology combined accounted for 79%of trial starts but declined by 8%compared to the overall market,which had 15%fewer starts

133、in 2023.The smallest declines overall were in oncology(3%),immunology(7%),and cardiovascular(7%)in 2023 compared to 2022,with trial starts exceeding 2020 levels in oncology,immunology and metabolic/endocrinology.COVID-19 starts dropped by 52%in 2023,bringing the starts to just one quarter of the num

134、ber of starts in 2020 at the peak of early pandemic research.Across therapy areas,the declines have been more concentrated in Phase I and Phase II clinical trials,except for infectious diseases(including COVID-19 and vaccines),where Phase III declines were greater.While some therapy areas had a more

135、 pronounced interruption of trial starts in 2020 from COVID-19,most had recovered in 2021 and 2022 and all had declines in 2023.Exhibit 14:Clinical trial starts by year and phase,20142023Notes:Phase II includes Phases I/II,II,IIa,IIb.Phase III includes Phase II/III and III.Terminated trials are incl

136、uded to track the activity still involved with theirinitiation,partial execution and termination.Trials were industry sponsored,interventional trials and device trials were excluded.CLINICAL TRIAL ACTIVITYClinical trial starts in key disease areas slowed with variations by phase,highlighting differi

137、ng maturity of research pipelinesSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.2,5002,0001,5001,000500020142023Oncology1,000800600400200020142023Immunology7006005004003002003Metabolic/endocrinology8007006005004003002003Neurology350300250200142023Cardio

138、vascular5004003002003Infectious diseases8007006005004003002003COVID-50020142023Vaccine infectiousdiseasesPhase IPhase IIPhase III20|Global Trends in R&D 2024:Activity,Productivity,and Enablers Rare disease trials declined less(8%)than larger population trials(20%)in

139、the past year.Oncology trials averaged 70%of rare disease trial initiations over the past decade;despite an 8%decline in 2023,the number of trials initiated remained above pre-pandemic levels and larger population oncology trials increased by 11%in 2023.Within rare diseases,immunology,cardiovascular

140、,and vaccines starts increased in 2023 by 8%,10%and 12%,respectively,compared to 2022,while other disease areas declined.In larger population diseases,all diseases except oncology had fewer starts in 2023,and all except vaccines had fewer starts than in 2020.Rare disease trials were 44%of trial star

141、ts in 2023 and an average 42%over the past decade,consistent with them having higher success rates than other research areas(Exhibit 38)and being 50%of U.S.NAS launches in the past five years(Exhibit 28).Exhibit 15:Industry sponsored interventional trials by start date,Phase I to III,20142023Notes:I

142、ncludes industry sponsored,interventional trials.Endocrinology includes diabetes,other endocrinology and GI/NASH.All others includes(womens health,other genitourinary excluding womens health,respiratory,hematology,and all others).Immunology includes autoimmune and inflammation.Oncology includes both

143、 solid-oncology and hematology oncology.Neurology is mental health and other CNS.Vaccines are infectious disease vaccines(i.e.,cancer vaccines are not included).Infectious diseases are not including vaccines or COVID-19.COVID-19 include any trials which mention COVID-19 and could include repurposing

144、 of existing therapeutics.CLINICAL TRIAL ACTIVITYRare disease trial starts are focused in oncology while diseases with larger populations focus on a wider variety of diseasesSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.4,0003,5003,0002,5002,0001,5001,00050004,0003,5003,0002,5002,0001

145、,5001,00050002023200020202002020212022Rare diseasesLarger population diseasesInfectious diseasesVaccine infectious diseasesCOVID-19OncologyImmunologyNeurologyCardiovascularNetabolic/EndocrinologyAll othersiqviainstitute.org|21 Oncology research

146、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 cancers declined 17%in 2023,clinical development for solid tumor cancers grew 1%when compared to 2022.Next-ge

147、neration biotherapeutics are increasingly under investigation for hematological cancers,with trials started globally in 2023 more than five times what they were a decade ago and accounting for 25%of the hematological-oncology pipeline.PD-1/PD-L1 which saw significant growth over the last decade,is u

148、p by 2%in 2023 when compared with last year in solid cancers.Despite being first developed in the 1960s,multi-specific antibody development for cancer treatment was minimal a decade ago and has grown significantly,representing 5%of both the hematological-oncology and solid tumor pipelines,indicating

149、 an increasing focus 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,representing 9%of the oncology pipeline in 2023 and allowing for targeting cytotoxic agents directly t

150、o cancer cells,improving on the non-specificity of older oncology products.Exhibit 16:Oncology clinical trial starts Phase I to III,by primary tested drug type,20142023Notes:Trials are industry-sponsored,interventional trials phase I,II,and III.Trials are assigned a type based on disclosed informati

151、on for the primary tested drug modality and mechanism.Segmentations are mutually exclusive.CLINICAL TRIAL ACTIVITYNovel oncology mechanisms,especially cell and gene therapies,ADCs and multispecific antibodies have risen to 25%of trialsSource:Citeline Trialtrove,IQVIA Institute,Jan 2024.2,0001,8001,6

152、001,4001,2001,00080060040020002,0001,8001,6001,4001,2001,00080060040020002023200020202002020212022Solid tumor cancersHematological cancersOther biotechMultispecific antibodyAntibody-drug conjugatePD-1/PD-L1 inhibitorSmall molecule kinase inhibit

153、orCell and gene therapyOther smallmolecule22|Global Trends in R&D 2024:Activity,Productivity,and Enablers In 2023,631 trials started for cell and gene therapies across all sponsor types;non-industry trials represented 36%of trial starts in 2023 with industry-sponsored trials(with or without non-indu

154、stry involvement)accounting for the other 64%.While non-industry trials have remained relatively flat over the last decade,industry-sponsored trials are up 276%from 2013 and 34%from five years ago.Much of this increase can be attributed to the growing research of CAR T-cell therapies,up from just fo

155、ur industry-sponsored trials started in 2013 to more than 150 starts for the last three years.CAR T share of trials dropped in 2023 to 39%of cell and gene therapy trial starts from a peak of 44%in 2022 as gene therapy trials grew.Industry and non-industry sponsors have been focusing their research i

156、nto different types of cell and gene therapies,but both have had a growing focus on CAR T-cell therapies,with 39%and 38%of industry and non-industry trials,respectively,started in 2023.The largest difference in research focus across industry and non-industry is in gene therapies,with 88 gene therapy

157、 trials(22%)started by industry in 2023 compared to just 26(12%)by non-industry.Other cell-based immunotherapies such as natural killer(NK),T-cell receptor(TCR),and tumor-infiltrating lymphocyte(TIL)cell therapies account for 12%of all trials in 2023;stem cell therapies accounted for 38%of non-indus

158、try trials in 2019 but have dropped to 20%of their trials in 2023,similar to the share of industry trials(16%in 2023).Exhibit 17:Cell and gene therapy clinical trial starts by type,20132023Notes:Includes Phase I,II,and III.Terminated trials are included to track the activity still involved with thei

159、r initiation,partial execution and termination.Trials are interventional trials.Trials are categorized by type based on disclosed information.Other cell-based immunotherapies includes T-cell receptor,tumor-infiltrating lymphocyte,natural killer,and dendritic cell therapies.Non-industry trials includ

160、e those sponsored by academic institutions,non-profits,and governments with no biopharma involvement.CLINICAL TRIAL ACTIVITYIndustry sponsored cell and gene therapy trials have more than tripled over the last decade while non-industry have grown 5%Source:Citeline Trialtrove,IQVIA Institute,Jan 2024.

161、450400350300250200040035030025020023200002020202220021IndustryNon-industryCAR T-celltherapyOther cell-basedimmunotherapyOther celltherapyGene therapyStem celltherapyiqviainstitute.org|23 Cell and gene therapies a

162、re being investigated across a range of diseases and modalities and by different types of sponsors and companies;across cell and gene therapy modalities,more than 90%of trials are run by academic institutions and startups,highlighting the important role these groups play in scientific discoveries an

163、d developing novel treatment options.Cell-based immunotherapies,including CAR T,are overwhelmingly being investigated for treating cancer with success in hematological cancers including several CAR T-cell therapies available commercially and potential in solid tumors being investigated in trials.Imm

164、unology,neurology,and metabolic/endocrinology diseases account for 53%combined of stem cell therapy clinical trials.Gene therapies often focus on inherited diseases,providing promise for patients with lifelong or debilitating diseases,with one example of recent success the restoration of hearing in

165、children across different studies in the U.S.and China with gene-mediated hearing loss.The size and type of the sponsor also varies by modality;emerging biopharma companies account for 55%and 59%of cell-based immunotherapy and gene therapy trial activity,respectively,but smaller shares in stem cell

166、and other cell therapies,whereas larger pharma companies have little involvement in stem cell and other cell therapy research,but account for 10%of cell-based immunotherapy trials and 21%of gene therapy trials.Exhibit 18:Cell and gene therapy trial starts by therapy area and company size,20192023Not

167、es:Includes Phase I,II,and III.Terminated trials are included to track the activity still involved with their initiation,partial execution and termination.Trials are interventional trials.Trials are categorized by type based on disclosed information.Company segment when two or more companies are inv

168、olved is determined by the larger sales segment.Emerging biopharma companies(EBP)are those with either R&D spend less than$200Mn or global sales up to$500Mn per year.Small companies have global sales between$500 million and$5Bn per year;mid-sized companies between$5Bn and$10Bn per year;and large com

169、panies exceeding$10Bn per year.CLINICAL TRIAL ACTIVITYCAR T-cell therapy clinical research is focused on oncology,while other diseases may benefit from other cell and gene modalitiesSource:Citeline Trialtrove,IQVIA Institute,Jan 2024.CAR T/cell-basedimmunotherapyStemcelltherapyOthercelltherapyGeneth

170、erapyCAR T/cell-basedimmunotherapyStemcelltherapyOthercelltherapyGenetherapyModality by therapy areaModality by sponsor sizeAcademicSmallLargeEBPMidAll othersWomens healthOphthalmologyCardiovascularOther infectious diseasesMetabolic/EndocrinologyCOVID-19ImmunologyHematological cancersSolid tumoursNe

171、urology24|Global Trends in R&D 2024:Activity,Productivity,and Enablers Metabolic and endocrinology studies include trials in diabetes,obesity and for NASH,sometimes with the target medicines being investigated in more than one of these areas.Diabetes dominates the field of metabolic and endocrinolog

172、y research,boasting a significant percentage of innovative contributions while comprising only 15%of non-novel substance in development in over the past five years.Trial activities around weight loss drugs have gained momentum in the recent years,with 68%increase in obesity trials start in 2023 comp

173、ared to 2022 and nearly doubled over the past five years.Obesity pipeline focused majorly on GIP/GLP glucagon receptor agonists,representing 35%of the drugs in development.NASH is the most severe form of non-alcoholic fatty liver disease(NAFLD),characterized by the accumulation of excessive fat depo

174、sits in the liver,where the role of insulin resistance in fat accumulation may be related to sponsors investigating diabetes drugs for NASH;the enduringly high unmet need in NASH has drawn growing interest from major pharmaceutical companies.3 Driven by significant attention from the biopharmaceutic

175、al sector in R&D investment,the NASH trials initiation has witnessed an 84%growth in 2023 compared to 2019,with majority of assets in early-stage of clinical development.Exhibit 19:Industry sponsored interventional trials by start date,20142023Notes:Trials may be included in more than one segment.GI

176、 NASH refers to a cluster of diagnoses related to Non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).CLINICAL TRIAL ACTIVITYObesity clinical trials in 2023 were up by 68%from 2022,and nearly doubled when compared to 5 years agoSource:Citeline Trialtrove,Jan 2024;IQVIA I

177、nstitute,Jan 2024.300250200150100500Phase IPhase IIPhase III40353025200806040200DiabetesObesityGI NASH20002020200202020020202120222023iqviainstitute.org|25Notes:Only the highest phase details of an ass

178、et are considered for creating the chart.*semaglutide is also being developed in Oral setting by Novo Nordisk.The same scenario can be with others.CLINICAL TRIAL ACTIVITYWith 124 drugs in development,over 35%drugs are GIP/GLP glucagon receptor agonists and 46%are orals Obesity is a major public heal

179、th threat globally;the rates for the disease have been increasing steadily over the last three decades and is likely to affect 1 billion adults by 2025.Of 124 drugs in development,eight are marketed and the remaining majority(55%)are in Phase I of development.The pipeline is dominated by the presenc

180、e of GIP/GLP Glucagon receptor agonists(45),which have gained popularity in the segment with the approval of semaglutide(Wegovy)in 2021.Of the total drugs,50%of development is happening in the subcutaneous segment and 46%in oral,promising greater convenience.Exhibit 20:Obesity pipeline by phase,targ

181、et and route of administrationSource:Citeline Trialtrove,IQVIA Institute,Jan 2024.Oral(57)SC(63)IV(3)Topical(2)Intranasal(1)Unknown(1)semaglutideliraglutidetirzepatidephenterminephentermine/topiramatesetmelanotideecnoglutidesurvodutidemazdutideorforglipronretatrutidecagrilintide/smaglutidesibutramin

182、e/topiramateCT-388CT-868pemvidutideGX-G6HM11260CdapiglutideHRS-9531HS-20094maridebart cafraglutidenoiiglutideVK-2735PB-718pegapamoglutideGMA 105K-757MDR 001danuglipronGSBR-1290dapagliflozinlicogliflozintesofensine/metoprololoxytocinS-309309orlistat/acarbose GSK-1521498INV-202APH-012NovOBARD 101miric

183、orilantpsilocybindiazoxide cholineRGH-706HU-6sucunamostatYso-1GLWL-01leucine+PDE5 inhibitorLMT1-48Xla1vutiglabridinCBL-514LIPO-102bimagrumabRZL-012orlistatcetilistatbupropion/naltrexoneECC5004HDM1002TERN 601XW 014AMG-786DR-10624GMA-106HM15136NNC-9204-1706 PB-119SAR425899 Ga-DO3A-VS-Cys40-Tuna-2TAK-0

184、94tirzepatideacetaminophenXW 004utreglutideUBT251CT-996YH 25724LR-19021 BMS-963272LY-3541105 GUB014295zevaquenabantcoated beads glucose&caffeine anhydrous coated beads glucoseNO-13065 BI-3006337LY3971297NNC-0480-0389RAY-1225 taldafgrobepalfaATX-304azelapragBI 1356225 CSTI-500DWP-306001ERX-1000RDX 00

185、2SCO-267SPI-62TLC-6740XEN-101TLC-6740BI1820237CIN 109CK-0045 ENT-03HEC-88473LA-GDF15LLF-580NGM-395CB-4211nisotirostideNN-9748amycretinGDD-3898GT001mibavademabpolidocanolDD-01Marketed(8)Phase III(8)Phase II(47)Phase I(61)GIP/GLP/Glucagon receptoragonist(45)Gastric and Pancreatic lipase Inhibitor(3)SL

186、C6(3)CALCR(2)MC4R(2)MGAT2/DGAT1(2)Opioid receptor antagonist(2)Cannabinoid receptor inhibitor(2)Unknown(9)Other(48)Amylinanalogues(6)pramlintideLY-3841136 ZP 8396AZD-6234amylin agonistlong acting26|Global Trends in R&D 2024:Activity,Productivity,and Enablers Neurology has significant growth with mor

187、e than 500 trials globally over the last five years,including products to treat neurodegenerative,neuromuscular,and psychiatric disorders.Much of the ongoing research is focused on Alzheimers and Parkinsons diseases,with 117 and 82 trials globally,respectively.In 2023,FDA approved omaveloxolone(Skyc

188、larys),the first drug to treat Friedreichs ataxia,a rare neuromuscular disorder that leads to loss of coordination,muscle weakness,fatigue.Currently marketed products for Alzheimers disease are focused on symptom management,with recent exceptions including aducanumab and lecanemab;however,most of th

189、e products under clinical development are disease modifying.Depression and other mental health conditions have become more prevalent and recognized,particularly during the pandemic,and account for an increasing amount of the neurology pipeline,with ongoing trials globally 65 for depression,20 for an

190、xiety.Other rare neurological diseases,such as amyotrophic lateral sclerosis(ALS)and Duchenne muscular dystrophy,continue to receive attention in the pipeline,with promising therapies in development.In 2023,88%of the neurology pipeline consisted of small molecule products,indicating their continued

191、utility in a rapidly evolving space.Next-generation biotherapeutics,such as cell and gene therapies,are increasingly being investigated for neurologic conditions,comprising 5%of the pipeline over last five years.Exhibit 21:Active trials in neurology Phase I to III by disease type,20192023Notes:Analy

192、sis includes trials started 2019-2023 with open,closed and temporary closed.Trials for more than one indication may be included in more than one disease area.Other neurology diseases trials have been hidden in the graph.CLINICAL TRIAL ACTIVITYNeurology research is focused on Alzheimers,Parkinsons an

193、d epilepsy,with a range of other often rare diseasesSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.Phase IIPhase IPhase III020406080100120140AlzheimersParkinsonsEpilepsyDepressionSchizophreniaMultiple SclerosisALSMuscular DystrophyMigraineAnxietySleep disordersSMAHuntington DiseaseAuti

194、smiqviainstitute.org|27 Depression trials represent 9%of active neurology trials during the 2019-2023 period(Exhibit 21),where major depressive disorders remain the most active segment with 40%of 2023 trial starts(not shown).Since 2021,overall depression trial starts have decreased by 43%while the m

195、ix of mechanisms of action has shifted significantly.Activity around other key depression segments includes a focus in treatment resistant depression in more than 14%of trial starts and postpartum depression in 2%of trial starts in 2023(not shown).Treatment-resistant depression research has ranged f

196、rom exploring therapy treatments using ketamine (a psychedelic)and deep brain simulation(DBS)to the recent discovery of a biomarker used as a measure indicator for treatment resistant depression disease recovery.4 There are a variety of emerging novel mechanisms becoming a focus,including serotonerg

197、ic psychedelics,kappa-opioids,NMDA psychedelics and neuroactive steroids,which together account for just under 58%of the 2023 trial pipeline.Despite psychedelics representing just over 15%of the trial starts last year,their uptake increased by 24%of the trial starts in 2023.Recent breakthroughs have

198、 identified non-hallucinogenetic psychedelic treatment potential in serotogenic psychedelics,which alone account for almost 32%of the active trials in 2023.5Exhibit 22:Depression clinical Phase I to III trials by segment and mechanism of action,20192023Notes:Trials may focus on more than one segment

199、 and depression segment analysis includes some double counting as a result.Trials could be included in other disease segments throughout the report.Trials are for CNS:Depression and CNS:Bipolar,include only Phase 1-3 trials,and non-bioequivalence(generic).CLINICAL TRIAL ACTIVITYDepression trial star

200、ts were 25%lower in 2023 than pre-pandemic with psychedelics being tested in nearly 40%of the 2023 trial startsSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.513967n=51n=39n=38n=67n=535338Novel selective serotonin reuptake inhibitors(SSRI)Other/UnidentifiedTRPC4 antagonistOrexin recept

201、or antagonistTypical antipsychoticAMPA receptor agonistNorepinephrine and dopamine reuptake inhibitors(NDRIs)Serotonin norepinephrine dopamine reuptake inhibitors(SNDRI)Selective serotonin reuptake inhibitors(SSRI)CytokinesAtypical antipsychoticNMDA agonist/antagonistNeuroactive steroids(NASs)NMDA P

202、sychedelicSerotonin and norepinephrine reuptake inhibitors(SNRI)Kappa-OpioidsSerotonergic psychedelics80706050403020202120222023Depression trial starts100%90%80%70%60%50%40%30%20%10%0%200222023Depression trial mechanisms of action,n=248 28|Global Trends in R&D 2024:Activity,Pro

203、ductivity,and Enablers New COVID-19 trials have dropped to less than 75%the level in 2020 as fewer new targets have been identified.Overall,non-COVID-19 infectious disease trial activity has focused on therapeutics to a greater degree than vaccines.Infectious disease trials show a dip in non-COVID-1

204、9 starts in early 2020,concurrent with the appearance of the first COVID-19 trials,but by mid-2020 had rebounded,nearly tripling those of infectious disease trial starts.In the past five years,the ID therapeutics segment has seen a decrease in the number of trials;however,there has been an increase

205、in the relative percentage of trial initiations for HIV,pneumococcal disease,HPV,influenza,and RSV.Conversely,the relative activity share in the bacterial infections segments has seen a decline,accounting for just 6%of the share in 2023;this trend underscores the ongoing deficiency of novel mechanis

206、ms and targets as well as the escalating risks associated with antimicrobial resistance.Exhibit 23:Infectious disease clinical trial starts by disease,20192023Notes:Industry Sponsored Interventional Trials,terminated trials included in the analysis.Other ID therapeutics and vaccines exclude COVID tr

207、ials.CLINICAL TRIAL ACTIVITYInfectious disease trials slowed to below pre-pandemic levels from both COVID-19 trials and other infection targetsSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.Other ID therapeuticsOther ID vaccinesCOVID-19 vaccinesCOVID-19 therapeuticsViral HepatitisRSVIn

208、fluenzaHPVPneumococcaldiseaseUTIBacterialinfectionHIVOther02004006008001,0001,2001,400200222023Trial starts0500300350400500450202220223Other ID Therapeutics,2022 vs.2023iqviainstitute.org|29 A total of 69 novel active substances(NASs)were launched globally in 2023,up

209、 six from the prior year and representing a return to pre-COVID-19 trends of NAS launches.A total of 362 novel active substances have launched globally in the past five years,bringing the 20-year total to 942 and highlighting an increasing gap between countries such as the U.S.,with 267 NAS launches

210、,and the EU4+UK,with 182,and China,which becomes the second largest with 192.While the number of NAS launches in China is rising,an increasing number are not available in other countries,reflecting both a rising domestic industry and a mix of reduced barriers and increasing incentives for multinatio

211、nal NAS launches.Global NAS launches excluding China-only NASs were up one to 52 in 2023;global launches averaged 60 per year in the past five years compared to 48 per year during 20142018.There is a growing gap between the drugs launched in the U.S.and those available to patients in the largest Eur

212、opean countries,with 113 drugs(42%)launched in the U.S.in the past five years that are not available in Europe,versus only 11 or 6%of European launches not available in the U.S.First-in-class NAS launches continue to emerge from research,including six first-in-class cell and gene therapies launched

213、in 2023,along with firsts in menopause,neurology and oncology.Emerging biopharma companies originated 56%of all new drugs in 2023 and launched 53%of them,less than in recent years but still more than in the first half of the decade.New drug approvals and launchesLaunches of novel medicines reach cou

214、ntries around the world at different times and while there have been hundreds of new drugs,many with significant clinical benefits,patients across countries dont have access to all of them.30|Global Trends in R&D 2024:Activity,Productivity,and Enablers A total 69 novel active substances(NASs)launche

215、d globally in 2023,indicating a rise of 10%from 2022 additionally representing a return to pre-COVID-19 levels.Oncology,neurology,and immunology have had rising shares of new launches in the past five years,with 204 of the 362 launches(56%)compared to 105 of 246(43%)from 2014 to 2018.Infectious dise

216、ases,including anti-bacterial,anti-viral,anti-fungal and anti-parasitic treatments,have included novel treatments for HIV,Ebola,and more recently smallpox,and are 11%of NAS launches over the last decade,with some year-to-year variability.NAS launches for COVID-19 have gone down from seven launches i

217、n 2020 to four launches in 2023.Of which three launches are only in China and one in the U.S.The total 201 oncology launches in the past decade include cell and gene therapies(11),as well as innovative modalities like antibody-drug conjugates(12)and bispecific antibodies(9).Neurology includes 68 dru

218、gs launches in 10 years,of which the recent launches in 2023 are for rare diseases including Pompe disease,Friedreich ataxia,Rett syndrome and Duchenne muscular dystrophy.Exhibit 24:Global launches of novel active substances(NAS)by therapy area,20142023Notes:A novel active substance(NAS)is a new mol

219、ecular 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 companies public statements.Oncology includes supportive care&diagnostics.COVID-

220、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 69 novel active substances(NASs)were launched globally in 2023Source:IQVIA Institute,Jan 2024.544936369Global NAS launches 2014

221、2023Immunology(40)All others(82)COVID-19(24)Gastrointestinal(31)Endocrinology(35)Infectious diseases(64)Cardiovascular(21)Hematology(42)Neurology(68)Oncology,incl.supportive care(201)504030202000222023iqviainstitute.org|31 A total of 69 novel active substa

222、nces have launched for the first time globally in 2023,bringing the five-year total to 362.Based on molecules in the late-stage pipeline,over the next five years an average of 6575 NASs are expected to launch annually,expanding the number of NASs launched globally by 325-375.6 U.S.launches totaled 5

223、7 in 2023,marking a 50%increase in the number of launches within a single year compared to the last year.This surge in activity has contributed to a five-year total of 267 launches.With 33 confirmed NAS launches,Chinas total for the past five years stands at 192.This is a significant increase compar

224、ed to the 99 launches from 20142018.As a result,China ranks second in the number of launches over the last five years.The four largest EU member countries(France,Germany,Italy,Spain)and the UK saw 22 launches in 2023,the lowest since 2014,totaling 182 in the last five years and representing a wideni

225、ng gap to U.S.and global NAS launches.Japan had 20 NAS launches in 2023,the lowest since 2014,and although launching sooner after global launch than earlier in the century,the country remains behind the U.S.and other major markets.Exhibit 25:Number of novel active substances(NASs)launched globally a

226、nd in selected countries,20042023Notes:Novel active substance(NAS)is defined as a medicine with at least one novel ingredient and is noted in the year it launches for the first time in the relevant geography.Fixed-dose combinations are NAS if one of the ingredients is novel,but would not be consider

227、ed NAS if both are previously available alone or in other combinations.Emergency use authorizations(EUA)are counted as NAS in the year the medicine became available to patients and no exclusion is applied for approval type.COVID-19 vaccines are counted as NAS based on which of the 8 subtypes of vacc

228、ine technology was used to create them.Launch of NAS in each geography are counted independently,meaning the totals for each geography include different products,and the global is a representation of distinct first global launches.NEW DRUG APPROVALS AND LAUNCHESA total of 362 novel active substances

229、 have launched globally in the past 5 years,bringing the 20-year total to 942Source:IQVIA Institute,Jan 2024.Global(942Total launched20042023U.S.(801)EU4+UK(624)China(572)Japan(582)050030035040020042008200920019202332|Global Trends in R&D 2024:Activity,Productivity,and Enablers

230、 There have been more than 30 NAS launches in China for a sixth consecutive year,making the five-year total now second after the United States in global launches,passing the four largest European countries and the United Kingdom.Updates to the national reimbursement drug list(NRDL),which shifted to

231、annual frequency in 2019,were a factor encouraging multinationals to launch in the country,with a backlog of global launches reaching the market in those years.More recently,most of the launches were by domestic companies that have no other major market launches around the world,including 50 of the

232、105 in the past three years.The significant increase in NAS launches in China has begun to reduce the gap to other key geographies,bringing more novel medicines to China sooner.From 2014 to 2018,the United States 224 NAS launches were 125 more than Chinas 99,whereas in the past five years,the U.S.ha

233、d 267 launches 75 more than Chinas 192.The key European markets(Germany,France,Spain,Italy and the UK)had 182 NAS launches in the past five years,10 fewer than China.In the past five years,129 of the NAS launches in China had also been launched in international markets at some earlier point,making t

234、hat international total below the key European and Japanese markets(Exhibit 25).Exhibit 26:NAS launches in China compared to other countries,20142023Notes:NAS Launch dates reflect the availability of a medicine in the relevant geography regardless of reimbursement status.Launches tracked in U.S.,EU4

235、+UK,Japan and China.China launches by year assessed for launch of those medicines before(or since)in other major markets.Some China-only launches may eventually reach other geographies.NEW DRUG APPROVALS AND LAUNCHESNAS launches in China in the past decade totaled 291,with 67 not yet launched elsewh

236、ereSource:IQVIA Institute,Jan 2024.00200020202120222023All other China NASChina launch and no other major markets22323iqviainstitute.org|33 Novel medicines do not launch in every country simultaneously,and increasingly ther

237、e is a gap where medicines launched in the U.S.are not widely available in other countries.In the past five years there have been 113(42%)U.S.NAS launches that have not yet been launched in the key European markets,while only 11(6%)drugs launched in Europe have failed to be launched in the U.S.The U

238、.S.is the most common first-launch country and there are often lags of a year or more to other country launches.These data mask these typical launch sequence patterns in the most recent two years,but older periods are indicative of more systemic patterns of incentives related to the relative commerc

239、ial value of markets.In the five years from 2014 to 2018,there were 38(17%)NAS launched in the U.S.that have not yet launched in Europe six to ten years later.In contrast,there are only eight(4%)drugs launched in Europe that have yet to launch in the U.S.Exhibit 27:NAS launches in the U.S.and EU4+UK

240、,20142023Notes:NAS launch dates reflect the availability of a medicine in the relevant geography regardless of reimbursement status.Launch dates in EU4+UK reflect the earliest of the five countries.U.S.NAS launches compared to their status in Europe.EU4+UK NAS launches compared to their status in th

241、e U.S.Information in most recent periods can be restated later and may change.NEW DRUG APPROVALS AND LAUNCHESSince 2018,113 U.S.NAS launches are not available in Europe,while 11 of Europe launches are not available in the U.S.Source:IQVIA Institute,Jan 2024.Not yet launched in EuropeLaunched same ye

242、ar as U.S.Launched in Europe before U.S.Launched later in EuropeNot launched in U.S.Launched same yearLaunched in U.S.before EuropeLaunched later in U.S.0070802014 2015 2016 2017 2018 2019 2020 2021 2022 20230070802014 2015 2016 2017 2018 2019 2020 2021 2022 2023U.S.NAS launche

243、s EU4+UK NAS launches11 not yet launchedin U.S.20192023113 not yet launchedin Europe 205072092264311134|Global Trends in R&D 2024:Activity,Productivity,and Enablers A significant number of f

244、irst-in-class medicines have become available,averaging 48%for the last five years,including 42%of those launched in 2023.Over the past five years,144 drugs launched with orphan drug designations,representing 54%of the 267 launches,indicating a significant focus on innovative medicines for rare dise

245、ases.Specialty medicines 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 75%of the launches in the U.S.in 2023.This proportion mirrors the levels observed in 2019.Of the 57 NASs la

246、unched in the U.S.in 2023,46%were biologics.This represents a decrease in the proportion of biologic launches compared to 2022,which stood at 61%.However,this percentage is comparable to the figures from the three preceding years.While less than 20%of NASs include reference to a predictive biomarker

247、 or have a companion diagnostic in their approval,many more medicines have some degree of precision,with targeted mechanisms dominating key therapy areas such as oncology.Exhibit 28:U.S.novel active substances(NASs)by product attributes and characteristics of clinical trials used for approval,201920

248、23Notes:Includes NASs launched in the United States 20192023 regardless of the timing of FDA approval.Orphans include 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 designa

249、ted indication.First-in-class is based on FDA classification.Predictive biomarkers and companion diagnostics based on FDA approval information.NEW DRUG APPROVALS AND LAUNCHESOver 40%of new launches in 2023 were first-in-class and about 50%were biologic,up from 35%5 years agoSource:IQVIA Institute,Ja

250、n 2024.First-in-class/OthersBiologic/Small moleculeOral/Other formsBiomarkers&diagnostics/OthersSpecialty/TraditionalOrphan/Non-orphanCompanion diagnostic at approvalPredictive biomarker0%20%40%60%80%100%2002220230%20%40%60%80%100%2002220230%20%40%60%80%100%200222023

251、0%20%40%60%80%100%2002220230%20%40%60%80%100%2002220230%20%40%60%80%100%200222023iqviainstitute.org|35 First in class molecules accounted for 42%of NAS launches in 2023(Exhibit 28)and nearly half(48%)of the launches over the past five years.Keeping up with the trend

252、in previous years,the majority(30%)of first in class molecules launched in 2023 were for oncology,followed by neurology(17%).In 2023,six first-in-class cell and gene therapies,including beremagene geperpavec(Vyjuvek),delandistrogene moxeparvove(Elevidys),donislecel(Lantidra),nadofaragene firadenovec

253、(Adstiladrin),omidubicel(Omisirge)and valoctocogene roxaparvovec(Roctavian)were launched,indicating an increase of 50%compared to the launch of three such therapies in each of the two preceding years.Additionally,first RSV vaccine(Arexvy),a first direct hormone-free treatment fezolinetant(Veozah)for

254、 menopause,and first allogeneic pancreatic islet cellular therapy donislecel Lantidra for Type 1 diabetes were launched in 2023.Exhibit 29:Therapy area share of first-in-class U.S.novel active substance(NASs),20192023Notes:The details on the clinical benefit summary of these 2023 launched first-in-c

255、lass molecules is given in exhibit 30 of the report.A novel active substance(NAS)is a new molecular or biologic entity or combination where at least one element is new;Includes NASs launched in the United States 20192023 regardless of the timing of FDA approval.First in class is based on FDA classif

256、ication.Immunology/allergy name harmonized to Immunology.NEW DRUG APPROVALS AND LAUNCHESFirst-in-class NAS launches continue to emerge from research,including notable gene therapies in hematology and oncologySource:IQVIA Institute,Jan 2024.Total first-in-class,20192023(128)Immunology(11)Others(13)CO

257、VID-19(4)Gastrointestinal(5)Endocrinology(6)Infectious diseases(7)Cardiovascular(8)Hematology(12)Neurology(19)Oncology,incl.supportive care(37)Dermatology(6)20004520022202336|Global Trends in R&D 2024:Activity,Productivity,and EnablersExhibit 30:First-in-class launch

258、ed in 2023NEW DRUG APPROVALS AND LAUNCHESEvery first-in-class NAS launched in the U.S.in 2023 provides a distinct therapeutic solution for its specific target indicationsFIRST-IN-CLASS NASINDICATIONMOACLINICAL BENEFIT SUMMARYCell&gene therapiesberemagene geperpavec(Vyjuvek)Dystrophic epidermolysis b

259、ullosaTranscription regulatorVyjuvek reported higher efficacy of 65%complete wound closure compared to placebo group(26%)at 24 wksdelandistrogene moxeparvove(Elevidys)Duchenne muscular dystrophyDystrophin replacements;Gene transferencePatients treated with Elevidys reported NSAA score of 2.6 Vs 1.9

260、points placebo treated patients after 52 wksdonislecel(Lantidra)Type 1 diabetesPancreatic beta cell replacements70%of patients met the composite efficacy end point were insulin independent at one year after transplantnadofaragene firadenovec-vncg(Adstiladrin)Bladder cancerAdenoviral vector-based gen

261、e therapy51%achieved a complete response by 3 months out of which 46%remain free of high-grade recurrence at 12 monthsomidubicel(Omisirge)Hematologic malignanciesAllogeneic hematopoietic stem cell therapyOmisirge reported a median time to neutrophil recovery of 12 days(87%recovery)Vs 22 days(83%reco

262、very)with standard cord bloodtofersen(Qalsody)Amyotrophic lateral sclerosisAntisense oligonucleotide targets ALS-SOD1Qalsody reduced CSF SOD1 protein,an indirect measure of target engagement by 35%Vs 2%in placebo groupvaloctocogene roxaparvovec(Roctavian)Hemophilia AAAV5 based gene therapy vectorRoc

263、tavian reported reduction in mean ABR with 0.5 bleeds/year for spontaneous bleeds and 0.6 bleeds/year for joint bleeds Vs SOCNeuro&Women healthfezolinetant(Veozah)Vasomotor symptoms in menopauseBlocks NKB signalingVeozah significantly reduced frequency and severity of the Vasomotor symptoms compared

264、 to placebo starting at week 4omaveloxolone(Skyclarys)Friedreichs ataxiaNF E2 related factor 2 stimulantsSkyclarys reported significant lower mFARS scores Vs placebo at 48 wks,with difference of-2.41 points and p-value of 0.0138.trofinetide(Daybue)Rett syndromeAnalog of glypromate/glycine proline gl

265、utamateDaybue reported significant improvement in MMRM analysis compared to placebo at 12 weeksBispecific Antibodymosunetuzumab(Lunsumio)R/R follicular lymphomaCD20 x CD3 bispecific monoclonal antibodyLunsumio reported ORR of 80%with mean duration of response of 2 years and Complete response was ach

266、ieved in 60%of patients.talquetamab(Talvey)Multiple myelomaGPRC5D x CD3 Bispecific monoclonal AntibodyAt lower dose of 0.4mg/kg,Talvey resulted in ORR of 73%and mean duration of response of 9.5 monthsOther Oncologycapivasertib(Truqap)Metastatic breast cancerAKT inhibitorTruqap in combination with Fa

267、slodex has reported to reduce disease progression or death by 50%Vs Faslodex alonenirogacestat(Ogsiveo)Desmoid tumorsGamma secretase inhibitorDisease progression reduced by 70%with ORR 41%,CRR-7%and median time of response of 5.6 monthsleniolisib(Joenja)Activated PI3K-delta syndromeSelective PI3K in

268、hibitorJoenja reduced lymph node size by day 85 and increased nave B cell count by 37%Vs PlaceboInfectious diseaseslenacapavir(Sunlenca)Multi drug resistant HIV-1 infectionCapsid inhibitorsSunlenca achieved an undetectable viral load($10Bn sales)and EBP($500Mn sales and$10 Billion annual sales)and t

269、heir clinical trial starts,highlighting the countries which are included in studies and comparing the most recent three years to the 20142016 period.Countries shown are the top 10 countries included across large companies.Trials were industry sponsored and interventional.PRODUCTIVITY ENABLERSLarge c

270、ompanies reprioritizing country use with significant utilization shifts in top 10 countries in the past decadeSource:Citeline Trialtrove,Jan 2024;IQVIA Institute,Jan 2024.All phases-%of total trialsRelative country-use 20212023,change from 20142016:Phase I%changePhase II%changePhase III%change%chang

271、e80%60%40%20%0%-20%-40%of Total Large Pharma Country-uses14%12%10%8%6%4%2%0%UnitedKingdomGermanySpainChinaUnitedStatesAustraliaCanadaFranceJapanItaly62|Global Trends in R&D 2024:Activity,Productivity,and Enablers The average number of countries used per trial has dropped by 5%for large and 15%for EB

272、P companies over the past decade and across the decade;EBPs use fewer countries per trial than large pharmaceutical companies.The total country/trial for all segments of the pipeline has decreased faster(30%)than for either customer segment as a function of the increasing number of EBP trials in the

273、 pipeline.EBPs have smaller subject,site and country“footprints”than large pharmaceutical companies across all three phases.The distinct EBP and large pharma subject,site,country“footprints”also demonstrate a linkage between number of subjects in a trial and the number of countries used.Whether due

274、to differences in therapeutic mix,as a necessity due to funding constraints between company types,or as a strategic decision to improve productivity,the increasing proportion of EBPs in the pipeline running trials with fewer subjects,sites and countries is likely contributing to the industry pipelin

275、e productivity gains.Exhibit 53:Average numbers of countries,sites,subjects in Phase I to III trials by company size,20142023Notes:Trials were industry sponsored and interventional.Diagnostics,behavioral therapies,supplements,devices,and medical procedures were excluded.Substantial lags have been no

276、ted in the reporting of numbers of subjects,sites,and countries which all rely on site selection,startup,and recruitment and early trial information may not reflect the full extent of the effort required.Therefore,subjects,sites,and countries have been adjusted in the most recent year(2023)based on

277、historic observations of this data latency.The most recent year is subject to change in subsequent periods.The Index of the average number of subjects,sites and countries is based on the largest values in the analysis which are set to 100.Value of 100 for subjects is 2162,115 for sites and 12 for co

278、untries.Large companies are defined as those$10 Billion in annual sales.PRODUCTIVITY ENABLERSEmerging biopharma trials have smaller subject,site and country footprint than large pharmaceutical trials across all phasesSource:Citeline Trialtrove,IQVIA Institute,Jan 2024.EBPLargeEBPLargeAll trialsPhase

279、 IPhase IIPhase III65432000222023Countries/trial by company segment All phasesAverage 20212023 number of subjects,sites and countriesindexed to 100-by phase and country segment SubjectsSubjectsSubjects0403020100SitesCountriesSitesCountriesSitesCountries201

280、51050iqviainstitute.org|63 The median number of patients enrolled in approval trials for 2023 launches with some form of expedited review was 22%that of trials for non-expedited launches.In the last five years,expedited approval trial enrollment has been 32%lower than for approval trials for non-exp

281、edited launches.Also in the last five years,the average median enrollment for approval trials for expedited launches has dropped by 52%and 42%for non-expedited launches,indicating that approval trial enrollment numbers are declining overall.More than half(53%)of the approval trials for 2023 NAS laun

282、ches have less than 200 subjects enrolled,and more than three quarters(83%)enrolled fewer than 1,000 subjects.There are multiple drivers of the ongoing decline in the number of subjects used by FDA for approval of NAS launches,including the mix of drugs receiving some form of expedited review,and co

283、rrelated with the pattern that emerging biopharma companies(EBPs)average smaller study enrollment(Exhibits 10,53).Exhibit 54:Number of subjects included in U.S.novel active substance(NASs)approval trials by review status and typeNotes:Expedited review includes accelerated approval,priority review,br

284、eakthrough therapy,and fast track designations,emergency use authorizations;orphan drug designation is not included as an expedited review but noted as it correlates with smaller numbers of trial subjects.PRODUCTIVITY ENABLERSFor NASs launched in 2023,83%included fewer than 1,000 subjects in trials

285、assessed by FDA for approvalSource:IQVIA Institute,Jan 2024.1002003,000Expedited Non-expedited201520142,5002,0001,5001,0005000201620172018Median number of subjects in clinical trials per NAS,20142023Percentage of NASs launched in 2023by the number of subjects includedin their approval trials20192020

286、2023202220215%12%14%16%34%19%n=57 64|Global Trends in R&D 2024:Activity,Productivity,and Enablers Sponsors and the FDA are increasingly focused on improving diversity representation and the reporting of these results in clinical trials.Despite these efforts,Black/African American and Hispanic patien

287、t inclusion continue to fail to reach U.S.demographic levels on average across interventional trials in the past decade.79 As racial and ethnicity demographics vary across countries,difficulties remain in finding true representativeness of the U.S population among global sites,especially for Black/A

288、frican Americans,but even with U.S.only studies,studies fail to achieve representativeness.Trial participation for Black/African Americans and Hispanic or Latino in U.S.only or global sites fall short on average of the 2023 U.S.demographics of 13.6%and 19.1%,respectively.Black/African American parti

289、cipation has been stable in the past few years,with a notable drop of 4%in U.S.-only sites trial participation between 2021(11%)and 2023(6%).Similarly,Hispanic inclusiveness has varied in the past decade and never reached U.S.demographic levels among both U.S only and global sites.Hispanic participa

290、tion reached its lowest point for the past decade in 2023,representing 9%in Phase II and III trials with U.S-only sites.In August 2023,the FDA drafted guidance calling on sponsors to complete data collection of underrepresented populations in post-market data collection should it be missing from pre

291、-market data.The effects of this recent effort to improve diverse representation in clinical trials remains to be seen in the years to come.10Exhibit 55:Phase II and III racial and ethnic inclusion indexed to U.S.demographics,20142023Notes:Includes all interventional Phase II and III trials with ind

292、ustry involvement and any U.S.sites listed on ClinicalTrials.gov starting after 2009 andcompleting between the start of 2014 and the end of 2023.Only trials with racial or ethnic data collected were included in calculation of Black/African American or Hispanic patient inclusion,respectively.Analysis

293、 includes 4,947 trials over the time period.Average U.S.Black/African American representation is 13.6%and U.S Hispanic or Latino representation is 19.1%.PRODUCTIVITY ENABLERSBlack/African American and Hispanic patient clinical trial representation dropped over the past decadeSource:U.S.Census Bureau

294、,2023;AACT Database,Dec 2023;IQVIA Institute analysis,Jan 2024.U.S.onlyGlobalU.S.onlyGlobal20%18%16%14%12%10%8%6%4%2%0%20%18%16%14%12%10%8%6%4%2%0%Hispanic or Latino(ethnicity)inclusionPercent of trial participantsBlack/African American inclusion13.6%in2023 U.S.census 19.1%in2023 U.S.census 20142015

295、20022202320020202120222023iqviainstitute.org|65 Black/African American and Hispanic inclusion varied in their top therapeutic areas;both were generally higher across all therapeutic areas in trials which were recruited exclusively in the U.S.,and both saw

296、the lowest levels of inclusion in oncology.Black/African American inclusion ranged from 22%(1.6 times higher than U.S.demographic)of patients in U.S.-only run cardiovascular trials to 3%(20%of the U.S.demographic levels)of globally run oncology trials.Hispanic inclusion ranged from 37%(1.9 times hig

297、her than the U.S.Hispanic demographic)in U.S.-run COVID-19 studies to 6%(31%of U.S.demographic)of globally run oncology trials.Notably,even in U.S.only site trials,Black/African American and Hispanic inclusion in oncology only reached 58%and 37%of the U.S.demographic levels,respectively.Poor inclusi

298、vity in oncology,which averages 36%of trial starts over the past five years,has an outsized impact on overall rates of inclusivity.The inclusivity disparities in the largest clinical development segments mirror some of the healthcare disparities in the U.S.overall and provide directed improvement op

299、portunities for stakeholders.11,12 In a November 2023 report,the FDA found that 87%of studies between April 2022 and April 2023 had a completed inclusivity plan,but only 6%of those contained required and acceptable diversity information,consistent with this analysis.13Exhibit 56:Phase II and III Bla

300、ck/African American and Hispanic patient inclusion by therapeutic area and geography,20192023Notes: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 2019 and the end of 2

301、022.Only trials with racial or ethnic data collected were included in calculation of Black/African American or Hispanic patient inclusion,respectively.PRODUCTIVITY ENABLERSClinical trial participation varies widely across therapeutic areas in U.S.vs.global trialsSource:U.S.Census Bureau,2023;AACT Da

302、tabase,Dec 2023;IQVIA Institute analysis,Jan 2024.U.S.onlyGlobalU.S.onlyGlobal40%35%30%25%20%15%10%5%0%40%35%30%25%20%15%10%5%0%Hispanic or Latino(ethnicity)inclusion by therapy area and locationTotalOncologyImmunologyInfectious diseasesCardiovascularNeurologyMetabolic/endocrinologyCOVID-19VaccinesA

303、ll othersTotalOncologyImmunologyInfectious diseasesCardiovascularNeurologyMetabolic/endocrinologyCOVID-19VaccinesAll othersPercent of trial participantsBlack/African American inclusion in clinical trials by therapy area and location13.6%in2023 U.S.census 19.1%in2023 U.S.census 66|Global Trends in R&

304、D 2024:Activity,Productivity,and Enablers In the past five years,larger companies have generally achieved worse racial and ethnic representation than emerging biopharma companies(EBPs)when sponsoring trials of U.S.only sites ranging between 1%to 10%of difference from U.S.demographics.Black or Africa

305、n American representation in trials decreased in the recent period,with EBP and larger company sponsored U.S.-only sites both worse in the more recent period.For the past decade,global site trials have increased their over-representation of Asians and Pacific Islanders by almost 3%during the 2014-20

306、18 period and almost 5%in the 20192023 period.With EBPs responsible for two-thirds of the R&D pipeline during the past decade and with their share continuing to grow,their imprint on racial and ethnicity representation in trials will only increase.Exhibit 57:Phase II and III racial and ethnic patien

307、t inclusion by company size and geography,20142023Notes:Emerging biopharma(EBP)companies are defined as those with either R&D spend$200 million or prescription sales up to$500 million.Companies with any active pipeline since 2014 were included.Large companies are those with global prescription sales

308、 exceeding$10 billion in the calendar year.PRODUCTIVITY ENABLERSLarger company sponsors are achieving worse representation in trials compared to emerging biopharma sponsorsSource:U.S.Census Bureau,2023;AACT Database,Dec 2023;IQVIA Institute analysis,Jan 2024.12.3%12.8%11.0%8.3%7.1%5.6%8.3%5.8%3.4%3.

309、4%3.5%3.5%6.0%7.2%9.3%6.4%13.6%1.3%19.1%11.0%0.3%1.6%0.5%0.3%0.2%0.5%0.7%0.8%12.7%11.2%9.9%9.1%10.6%12.0%11.4%13.0%2023 U.S.census Larger companies GlobalEBP U.S.EBP GlobalLarger U.S.companies2002320%15%10%5%0%Black or African AmericanHispanic or Latino(ethnicity)20023201420182

310、002%10%8%6%4%2%0%20%15%10%5%0%2.0%1.5%1.0%0.5%0.0%Asian&Pacific IslanderAmerican Indian or Alaska Nativeiqviainstitute.org|67 Novel trial designs,including umbrella,basket,master,and adaptive protocols,form a foundational part of the clinical trial pipeline and have been includ

311、ed in 18%of trials since 2021.Novel trial design utilization is highest in oncology trials,accounting for 29%of these trials in 2023,down from a peak of 32%in 2022 but up from 13%in 2014.Infectious disease saw a spike in novel trial design use through the pandemic as COVID-19 trials widely leveraged

312、 master protocols and adaptive structures to enable parallel processing,accelerate program data collection,and improve decision-making,but have returned to and remained steady at pre-pandemic levels since 2022.Neurology trials have also been increasingly using novel trial design strategies since 201

313、4,with strategies employed in 12%of the 2023 neurology trials.It is likely that increasing use of novel trial designs will continue to contribute to industry productivity as NTDs build a foundation across critical therapy areas,increasing knowledge,failing faster,and consistent with faster developme

314、nt timelines for clinical programs that include combined phases often enabled by NTD.Exhibit 58:Novel trial design starts by year and therapy area,20142023Notes:Novel trial designs include umbrella,basket,adaptive,master protocol,dose escalation+dose expansion studies using a range of keyword string

315、s.Share based on industry interventional studies plus novel trial design studies from non-industry sponsors.Most non-industry sponsors are understood to have received some degree of funding from industry in these trials.Novel trial design share is based on all industry/interventional trials plus any

316、 novel trial design studies.In the studies analyzed,non-industry novel trial design studies represented 16%of these studies.PRODUCTIVITY ENABLERSNovel trial designs have averaged 18%of trials since 2020,led by oncology with over 29%novel designsSource:Citeline Trialtrove,IQVIA Institute,Jan 2024.Car

317、dio/Metabolic/EndocrinologyAll othersInfectious diseases,vaccines,COVID-19NeurologyImmunologyOncology20%18%16%14%12%10%8%6%4%2%0%201435%30%25%20%15%10%5%0%200020020202%15%15%15%15%15%19%18%18%18%Novel trial designsNovel trial designs

318、share of therapy area 68|Global Trends in R&D 2024:Activity,Productivity,and Enablers Real-world evidence(RWE)and real-world data(RWD)represent significant opportunities to contribute to improved clinical development program productivity,including use in regulatory approval applications.It is unders

319、tood that a large percentage of submissions include RWE components in the information provided to the FDA14,but many fewer studies are explicitly noted by the FDA as a basis for approval.Over the past decade,RWE has been publicly cited in approval letters as a basis for approval by FDA for new appro

320、vals or expanded use of existing drugs 46 times.Approvals citing RWE have most often been in rare diseases,oncology and neurology studies,and have non-interventional designs or act as external controls.The FDA has issued multiple guidelines on the use of RWD/RWE in clinical development since the rel

321、ease of the 21st Century Cures Act(2016),including multiple publications in 2023 on use in medical device development,and finalization of 2021 guidance on use in medical product development and further refinement of data standards for use of RWD as RWE.Future expanded utilization of RWE,decision-mak

322、ing transparency,and pilot program agency partnerships are expected following the September 2022 guidance on submissions of RWE and RWD15 and the October 2022 FDA announcement of the Advancing RWE Program in fulfillment of PDUFA VII obligations.16Exhibit 59:FDA approvals based on real-world evidence

323、(RWE),20142023Notes:Collected from public sources relating to the approval trials for medicines.Data collected under a treatment IND or expanded access protocol has been considered a form of RWE by the FDA,such as in rare disease settings where there is little chance of a prospective trial.RWE appro

324、vals shown here include those granted after approval(e.g.,carglumic acid 2010 RWE but drug was a 2006 launch).Analysis includes some double counting where a drug may have had more than one type.PRODUCTIVITY ENABLERSBoth sponsors and the FDA are increasing their focus and incorporation of RWE for reg

325、ulatory decision-makingSource:IQVIA Institute,Jan 2024.OncologyNeurologyInfectious diseasesImmunologyOtherExpanded accessRCT pragmatic&RWD supplementsExternal control armNon-interventional studyRare diseases84Study design type,n=46Therapy areas,n=4639%26%13%7%2%13%iqviainstitute.org|69 The relative

326、discoverable use of remote,virtual or decentralized methods in clinical trials continued to dip in 2023 to resume modest pre-COVID-19 growth trajectory.Early 2020 saw a very sharp increase in reported decentralized methods that mirrored a sharp increase in total trial activity driven by COVID-19 the

327、rapy and vaccine development.Removal of COVID-19 trials from the analysis shows that trials with decentralized methodologies dropped in 2020 and 2021 relative to total non-COVID-19 trials,suggesting that COVID-19 trials may have taken up all decentralized trial“capacity.”Non-COVID decentralized tria

328、l use rebounded in 2022 and 2023,giving some indication that though detected at relatively low levels,decentralized trials may have become more established resulting from a critical need and rapid implementation during the pandemic.RVD trials run between 2019 and 2023 are most heavily focused on COV

329、ID-19 followed by neurology and immunology.Exhibit 60:Trial starts for all trials and remote,virtual or decentralized trials(RVD),20142023Notes:Trials which have a number of decentralized features often dont disclose those in trial registry information.Analysis includes industry and non-industry,and

330、 interventional and non-interventional trials to enable identification of utilization trends.PRODUCTIVITY ENABLERSTrials which are remote,virtual or decentralized have been increasing in line with the industry trial starts but focus in different diseasesSource:Citeline Trialtrove,IQVIA Institute,Jan

331、 2024.CardiovascularAll othersInfectious diseasesNeurology(inc mental health)COVID-19Vaccine infectious diseasesMetabolic endocineImmunologyOncologyTotalTotal excluding COVID-19RVD excluding COVID-19RVD33%17%12%8%7%5%4%3%11%0070809010001,0002,0003,0004,0005,0006,0007,0002001720

332、02120222023RVDTotalRVD Trials 20192023,N=22870|Global Trends in R&D 2024:Activity,Productivity,and Enablers Start-up and established healthcare companies are applying AI/ML technology to leverage growing chemical,biological and patient datasets to accelerate and improve drug target and dr

333、ug selection across the entire drug discovery continuum,with a set of most-used applications emerging in the clinical pipeline.The number of trials involving molecules that were discovered and researched by a cohort of AI/ML research focused companies with the use of AI/ML technology has been increasing over the last five years.This pipeline of AI/ML-originated molecules shifted to later stage dev