心灵超越物质：中枢神经系统创新的增长势头

Mind over matter: The growingmomentum of CNS innovation How innovators are beating the odds in a high-stakestherapeutic area MARKUS GORES, Vice President, EMEA Thought Leadership, IQVIASTEFAN LUTZMAYER, Senior Consultant, EMEA Thought Leadership, IQVIA Table of contents Introduction1Unmet need is accelerating1Pushing the frontiers of CNS innovation3Neuroinflammation3The gut-brain axis4Psychedelics5Digital health6Innovation momentum and the competitive landscape in CNS9Deep dive: CNS indication highlights13I.Alzheimer’sdisease13II. Mental health15CNS market outlook19How to succeed as a CNS innovator20References22About the authors26 Introduction The global burden of illness related to Central NervousSystem (CNS) disorders keeps rising unabatedly, withhugeeconomicimplications.By2030,theglobaleconomic cost of mental health conditions alone isprojected to reach $6 trillion,1for example, while theeconomic burden of Alzheimer’s and related dementiasis estimated to rise to $4.7 trillion.2 These extraordinary numbers reinforce the urgentneed for novel therapeutic interventions to treatCNS disorders, however, the title of our previouspublicationfrom2023,“Twostepsforward,onestep back: The long road to success in CNS”3stillrings true today, as innovators continue to navigatethe high-stakes roller coaster of developing andcommercialising new CNS therapies. Unmet need is accelerating Notwithstanding well publicised setbacks, numerousexamplesillustratethesignificantprogressmadeinexpanding CNS therapeutic options to give hope topatients, their families and caregivers. The global burden of illness caused by mental healthandneurologicaldisordersissignificantandcontinuesto rise sharply. For 2021, the WHO5estimated thecombined long-term impact on health-relatedquality of life of non-communicable mental healthandneurologicalconditionsas304milliondisability-adjusted life years (DALYs) globally, an increase of26% since 2010. For context, this burden considerablyexceeds the 2021 estimate of 270 million DALYsglobally for all malignant neoplasms. For example, the approval of Cobenfy representsthefirstnewapproachfortreatingschizophreniainover30years,bytargetingcholinergicreceptorsasopposed to dopamine receptors; NMDA-targetingSpravato (esketamine) for treatment-resistantdepression and major depressive disorder with suicidalideation is well on its way to reach blockbuster statusin2025andsignifiesacaseinpointforthepotentialofpsychedelics as valuable, and commercially viable, CNStherapies; while the approvals of amyloid-targetingtherapies Leqembi and Kisunla, and the Lumipulse Gtest,asthefirstbloodtestfordiagnosingAlzheimer’s,4highlight the ongoing, albeit slow, progress in tacklingthis devastating disease. Consistent with our previous analysis based on 2019data, Alzheimer’s continues to be a major driver of thefuture global disease burden with a 54% increase inDALYs between 2010 and 2021. However, between the 2019 and 2021 data sets fromthe WHO, several conditions have seen dramaticacceleration in their respective burden of illness whencomparing change in DALYs for the time periods of2010-2021 vs. 2010-2019: 47% for Parkinson’s, upfrom35%;54%fordrugabuse,upfrom33%;36%fordepression,upfrom16%;and34%foranxiety,upfrom11% (see Figure 1). In this white paper, we will explore the latesttrends in CNS innovation, including a deep dive intoselected therapeutic breakthroughs, and provide anoutlook on the competitive landscape and the CNSmarket opportunity. The particularly pronounced acceleration in thedisease burden of depression, anxiety and drug abusebetween 2019 and 2021 overlaps with the beginningof the COVID-19 pandemic as a likely importantcontributor to this dynamic, and it highlights the scaleof the growing global mental health crisis. however, innovators face serious challenges duringboth development and commercialisation of novel CNStherapies, for example: •Limitations in translational animal modelsand validation of CNS drug targets, resultingin historically higher failure rates in CNS drugdevelopment compared to other therapy areas. Itisimportanttonotethat80%ofpeopleaffectedby mental illnesses live in Low- and Middle-IncomeCountries (LMIC), with LMICs representing 9 of the top10 countries ranked by absolute burden of illness (totalDALYs) related to mental health disorders.6,7Amongthe top 20 non-communicable diseases, depressionand anxiety rank 12th and 15th by disease burden,respectively, in Upper-Middle Income Countries (UMICs),while depression ranks 17th and 18th in Lower-MiddleIncome Countries (LrMICs) and Low-Income Countries(LICs), respectively.8At the same time, the World HealthOrganization estimates that over 75% of the populationwith mental health disorders in LMICs do not haveaccess to the right care, with the provision of mentalhealth services held back by a combination of factors,including health policy, funding and resources, but alsocultural barriers and social stigma.9 •Patientidentificationandrecruitm