新药，新见解：加速神经科学的新前沿

New Medicines,Novel Insights:Accelerating theNew Frontiersin Neuroscience An Executive Summary In this report Nearing the tipping point in neuroscience3 Innovative trial design4 Navigating market access in neuroscience5 Risk mitigation through feasibility assessment7 Strategies for expanding trial diversity8 Precision psychiatry: critical for early interventionand disease management9 Early identification of Alzheimer’s Disease10 Regulatory pathways for psychedelic drugs11 Nearing the tipping point in neuroscience advances in treating multiple sclerosis (MS), where limitationsof the mainstream Expanded Disability Status Score (EDSS)and Annualized Relapse Rate (ARR) led researchers andpatients to advocate for more sensitive, disease mechanism-related, and patient-relevant endpoints. Judging from the enormous progress being made in treatmentmodalities and better understanding of how the brainworks, neuroscience research has reached a major tippingpoint. At Parexel, we understand how the research in thischallenging field is poised to accelerate scientifically, clinically,and commercially, much as cardiology and oncology diddecades ago. More reliable biomarkers.There is a lack of reliable and easy-to-access biomarkers for early diagnosis and disease treatmentmonitoring. The development and validation of wide spectrumof biomarkers — genetic, molecular, clinical, digital — willaccelerate development of precision medicine in neuroscience. At a tipping point, as progress accelerates, we still haveto navigate increasingly complex challenges in clinicaldevelopment to deliver safe and effective treatments to thepatients who need them. What will carry us forward? Boldness and courage.Understanding comes with trial anderror, including high-profile, expensive failures. It comes witha committed investment in research. At Parexel, we advisesponsors on how to minimize risk and accelerate developmentusing innovative trial designs and novel endpoints. Workingclosely with regulators and conducting rigorous feasibilitytesting can mitigate the risks in these approaches. Urgency.The neuroscience community must communicatean urgency commensurate with the burdens and crises thesediseases impose on individuals and societies.Neurological andpsychiatric diseases often evolve slowly, but time matters;disease-modifying treatments must start early to impactprogression.The World Health Organization estimatesthat half of adult mental health disorders start by age 14,and depression and anxiety are a leading cause of illness anddisability among adolescents globally.1 In this report, Parexel experts share insights and best practicesthat can help drug developers navigate complexity and movecloser to achieving their goals — all while staying focused onthe patient journey. Better endpoints.Endpoint selection and interpretationremain significant challenges. We can apply lessons from Innovative trial design Neuroscience trials typically remain traditionalbecause of the heterogeneity of neurologic,neurodegenerative, and psychiatric diseases andthe relative absence of actionable biomarkers.Yet adaptive approaches and biomarkers couldoptimize trial designs and make developmentmore efficient.2 Recent advances in the field, including theemergence of new blood and imaging biomarkers inMS, Alzheimer’s disease (AD), and major depressivedisorders (MDD), suggest the time has come forinvention and cross-fertilization. At Parexel, weadvise sponsors on using innovative trial designs,novel biomarkers, and external data to accelerateneuroscience drug development. Navigating market access in neuroscience While focus on the patient during clinical phases is paramount,a new treatment will benefit a broad population only if payersprovide access. Therapeutics in neuroscience pose a specialchallenge in this regard. Despite great strides in understandingneurological and psychiatric conditions, most conditions progressslowly, and the symptoms are not easily captured throughendpoints that clearly demonstrate immediate benefits. Thiscreates a new paradigm both for regulatory approval and payeracceptance since we are not addressing survival or a set ofclinical symptoms. For this reason, we advise our clients to start planning marketaccess strategies as early as possible, ideally when entering theclinic. At the very latest, the strategy should be in place as Phase Istudies conclude and the transition to Phase II begins. The initialpriority is to identify the target product profile. What is the unmetmedical need? What patient segments are being addressed andfor what symptoms? And beyond the regulatory framework, whatis the caregiver burden and how does this impact utilization ofother healthcare services? Determining the target patient profile andultimately, the value story, requires a deepunderstanding of the patient journey and theoutcomes that the patient considersmeaningful and beneficial. This knowledge drives thestrategy for data generation and