Galien Golden Jubilee Forum – USA2021

Oct. 28th, 2021
9AM – 10AM

In-person registrationLive broadcast registration

Ann Graybiel, Institute Professor, Department of Brain and Cognitive Science, MIT

Diana Gallagher, Head of External Innovation, Biogen
Dan Grossman,
Managing Director and Senior Partner, Boston Consulting Group
Kelsey Martin, Director, Simons Foundation Autism Research Initiative (SFARI)
Michel Pairet, Member of the Board of Managing Directors – Innovation, Boehringer Ingelheim
Jay Stamatis, Vice President, Head of Business Development and Acquisitions, AbbVie


Future pathways in translational medicine – “Academic-Industry Collaborations in CNS Diseases”

Topics for Discussion

  • Current state of CNS science — is our expanding knowledge of underlying brain and nervous system biology poised to yield real breakthroughs in clinical medicine? What CNS scientists can learn from other disciplines?
  • Highlights of new platform modalities and approaches to raise the standard of care in therapeutic areas most resistant to new medicines innovation, including Alzheimer’s and schizophrenia. What kind of treatments – or cures – can patients with neurological disorders expect to see a decade from now?   Does CNS disease prevention have a viable place on the horizon?
  • Examples and best practices from successful R&D partnerships between industry, academia and other participants in the CNS research ecosystem. What actions are needed from governments, regulators – and society at large – to surmount existing barriers to CNS research and reverse the cycle of late-stage development failures that slow progress for patients?

Issue Background

Diseases of the central nervous system (CNS) comprise a vast array of complex conditions that together account for a growing burden of death and disability worldwide.  The CNS clinical spectrum includes Alzheimer’s and dementia; epilepsy and related seizures; cerebral stroke; movement disorders like Parkinson’s; Multiple Sclerosis (MS), an immune-mediated nerve damage syndrome; psychiatric brain irregularities, led by schizophrenia; and even the common headache and its debilitating analog, migraine.   Overall, one in four Americans today experience at least one of these conditions.  The centrality of CNS to human biology has been expressed in stark terms during the COVID-19 pandemic, where upwards of 80% of US patients hospitalized with the virus have experienced a variety of neurological impairments, from “brain fog” and loss of smell to dementia, stroke and coma.

Many CNS diseases are linked to age and their effects on patients tend to be long-term, which means the public health burden is enormous. According to the latest 2019 Lancet Global Burden of Disease study, neurological disorders are now the leading cause of disability and the second leading cause of death worldwide for patients over age 50.    In the US alone, the cumulative cost of treating the 6.2m patients with Alzheimer’s is currently $355bn; that figure is estimated to rise to $1.1tr by 2050, along with a doubling of the diagnosed patient population to 13m.

Given this growing burden of disease, advances in prevention and treatment for CNS disorders will be critical to countering a global demographic shift to an older population.  In this regard, the relevance of brain science and neurologic research to improving population health and well- being is universal: it’s as important to low- and middle-income countries as it is for the US. Hence expectations are high for the CNS segment to emerge as a priority in leading the next 50 years of biomedicines innovation.

The goal is particularly important because progress in treating major conditions like Alzheimer’s, Parkinson’s, depression and schizophrenia has been sporadic at best.  Virtually all medicines for these high-profile disorders address symptoms only – clinicians and patients are still waiting for breakthroughs that attack the underlying disease.   In February 2018, the US FDA issued a draft industry guidance designed to speed up the approval of novel drugs for neurological conditions not addressed by available therapies.  Despite some incremental wins in areas like amyloid-based blood diagnostic agents for Alzheimer’s, innovation in the CNS sector has failed to progress beyond the current standard of care. The FDA in June approved Biogen’s Aduhelm (aducanumab-avwa) as the first and only treatment to address a defining pathology of Alzheimer’s disease. Regulators had not approved any drugs for the disease since 2003, a nearly 20-year gap in the Alzheimer’s disease armamentarium.

There is little doubt that CNS research presents daunting obstacles due to the complex biology of the brain, the spine and the neural networks whose biochemical pulses control everything that makes us human: from thought, memory, movement and emotions to the mechanics behind breathing, heart rate, hormonal changes and body temperature.  Several decades of statistics from the Tufts University Center for the Study of Drug Development show that clinical drug development programs in CNS are both more costly and have the highest failure rate of any therapeutic area in medicine.

The main factors explaining this include the variable, multi-faceted aspects of the etiology of CNS disease. This in turn hampers a comprehensive understanding of biologic and genetic properties that drive disease incidence and progression. Of equal concern is the multiplicity of side-effects that accompany the human phases of drug development and specific challenges facing CNS clinical trials, such as designing the right placebo response, incorporating soft endpoints and targeting the right patients for enrollment.   Another persistent problem specific to CNS has been the inability of researchers to create drugs able to penetrate the blood-brain barrier to deliver the appropriate therapeutic response.     Each of these challenges have made working in the CNS space a high-risk activity, even for the largest of big pharma companies, resulting in the shut-down of some major private-sector R&D programs over the past decade.

However, the resources devoted to CNS research show signs of growth.  Big pharma and biotech are   opting to work in R&D partnerships to lower risk and apply existing resources more efficiently to advance their CNS targets to market approval. Basic discovery is flourishing at the academic level, paced by more government and philanthropic funding; recent examples include the creation of new integrated neuroscience research centers at Massachusetts Institute of Technology (MIT) and Washington University in St. Louis, MO.  Finally, deep-pocketed advocacy groups like the Alzheimer’s Association and the Brain and Behavior Research Foundation are emerging as active participants in the pursuit of research solutions.

Another positive is the abundance of research areas to explore.  Combinations of existing drugs are a major focus of investigation that has just begun to be tapped.  Building on progress in other therapeutic disciplines, RNAi and related gene and immunotherapies are showing promise as a treatment platform for many CNS conditions, from Alzheimer’s and Parkinson’s to schizophrenia, which is already known to have roots as an inherited genetic disorder. Diagnostic biomarkers are another avenue that might open fresh insights into the prevention of CNS diseases, with huge potential as a cost-saver for health systems.