Therapeutic Development in the Absence of Predictive Animal Models of Nervous System Disorders Proceedings of a Workshop (2017) / Chapter Skim
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5 Private-Sector Thresholds for Investment in Neuroscience Clinical Trials
5 Private-Sector Thresholds for Investment in Neuroscience Clinical Trials
Pages 33-44
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From page 33... ...
. • Public‒private partnerships and other precompetitive consortia offer a neutral ground where multiple stakeholders can share the risks and costs associated with developing tools and resources and answering critical questions that cross multiple drug devel opment programs (Sauer, Sherer)
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From page 34... ...
Poor understanding of disease biology remains the most critical gap hindering the development of new central nervous system (CNS) drugs, said David Michelson.
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The second example was a clinical trial designed to connect circuit function to domains of dysfunction. Balice-Gordon and colleagues designed a discovery human neuroscience study with multiple endpoints across several modalities, and a parallel study with a clinical functional rating scale as an endpoint.
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For example, iPS cells enable both hypothesis building as well as assessment of safety and toxicology, and offer the potential to address disease heterogeneity, which has proved to be a major hurdle in drug development for nervous system disorders. Nonhuman disease models remain essential for translation, and the nonhuman primates discussed earlier, coupled with novel methods for inducing relevant phenotypes (e.g., Clustered Regularly Interspaced Short Palindromic Repeats [CRISPR]
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From page 37... ...
. Martin drew a sports analogy to explain the problem: while drug discovery engines in many companies generated numerous molecules, the process was more akin to "playing darts blindfolded" rather than producing many "shots on goal." Martin underscored the importance of risk versus cost trade-offs when considering whether to invest in a particular clinical development program.
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Saage Therapeuttics also appllied the "learnn and confirm m" paradigm to study multiple m indiccations for a single moleccule that had bbeen shown eef ous in patientts with refracctory epilepsyy. A positive signal from an ficacio explorratory study of four patieents with posstpartum deprression led tthe compaany to conducct a 21-patien nt, placebo-coontrolled Phasse II study coonductedd within regu ulatory guidelines with a widely usedd endpoint (tthe Hamiltton Depressio on Scale)
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In a later presentation, Doug Cole noted that small companies often do not have access to resources such as clinically annotated tissue, which could help better elucidate disease course and natural history. He suggested that a national repository of clinically annotated tissue, for example, could be enormously enabling for small companies.
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PUBLIC‒PRIVATE PARTNERSHIPS AND OTHER PRECOMPETITIVE CONSORTIA While better tools are needed for dose selection, signal detection, target selection, and validation, John Michael Sauer, executive director of the Critical Path Institute's (C-Path's) Predictive Safety Testing Consortium (PSTC)
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to test whether antisense oli gonucleotides can be delivered to motor neurons to prevent the production of toxic proteins. The work completed by this part nership in precompetitive space has since enabled the advance ment of antisense oligonucleotide treatments to clinical trials for spinal muscular atrophy, amyotrophic lateral sclerosis, and Hun tington's disease.
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The model has been qualified by the European Medicines Agency and endorsed by the FDA for the purpose of simulating clinical trials to test different trial design parameters. 3 For more information, go to https://cenc.rti.org (accessed November 18, 2016)
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INCREASING THE PROBABILITY OF SUCCESS FOR DRUG DEVELOPMENT Martin listed five policy considerations that could increase the probability of success, reduce development costs, and increase pay-off and predictability. Commitments to these five considerations are needed from industry, academia, and public‒private partnerships, he said: • Create risk-sharing models for target validation.
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From page 44... ...
Fox Foundation. They surveyed the field to identify the four or five most impactful questions in Parkinson's disease basic biology, natural history, biomarker development, and clinical instrument development and validation.
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