FDA formalizes new partnership to advance neurodegenerative disease research

The FDA took further steps toward a comprehensive approach to rare neurodegenerative diseases today, announcing a public-private partnership among the FDA, National Institutes of Health, and the nonprofit Critical Path Institute (C-Path). C-Path will serve as the convener for efforts including patient-focused drug development and speeding the development of therapies by use of the FDA’s rare disease accelerator and analytics platforms.

BY KARI OAKES | SEP 14, 2022 11:59 PM EDT

Background on the ACT for ALS Act

  • The Accelerating Access to Critical Therapies for Amyotrophic Lateral Sclerosis Act (ACT for ALS) was enacted on December 23, 2021. ACT for ALS provides for grants for ALS research, calls for establishing public-private partnerships to advance disease understanding and drug development for rare neurodegenerative diseases, and directs the FDA to publish a 5-year action plan laying out operational plans for accomplishing the goals of ACT for ALS.
  • An action plan announced in June 2022 serves as the “blueprint” for the agency’s plans to put more resources into overcoming drug development challenges in a number of rare neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). The well-funded 5-year plan includes a roadmap for modernizing and expanding regulatory science in the neurodegenerative rare disease space.
  • The provisions of the FDA’s action plan map out to requirements in ACT for ALS to “foster the development of safe and effective drugs that improve or extend, or both, the lives of people living with ALS and other rare neurodegenerative diseases; and facilitate access to investigational drugs for ALS and other rare neurodegenerative diseases.”
  • Other provisions within the act call for the FDA to identify staff to lead and oversee “interactions and collaboration between FDA and stakeholders,” to include the external biomedical research community as well as sponsors and patients. Also, the agency is tasked with considering “cross-cutting clinical and regulatory policy issues,” as well as enhancing cross-agency and public-private collaboration and engagement. In a key provision of ACT for ALS, the FDA is charged with identifying “key regulatory science and policy issues critical to advancing development of safe and effective drugs.”
  • Throughout the 5-years of the action plan, the FDA will work to develop disease-specific science strategies. These will examine “substantive issues in drug development” for specific rare neurodegenerative diseases that will be identified by means of a needs assessment to see which disorders “would benefit from heightened coordination across the Agency,” according to the plan.
  • Existing FDA regulatory science resources will be brought to bear on the goals of the action plan. In addition to the ARC program, the FDA anticipates that complex innovative trial design meetings and critical path innovation meetings will come into play in speeding development of therapies for rare neurodegenerative diseases. Other existing programs that will be tapped include the fit-for-purpose initiative, the pilot program for model-informed drug development paired meetings, the patient-focused drug development program, the data and analytics platform of the rare disease cures accelerator, and the real-world evidence program.

The first science strategy to come out of the action plan addresses ALS, and will serve as a roadmap for later disease-specific strategies

  • The first focus is to “improve characterization of disease pathogenesis and natural history,” an important first step for ALS since the pathophysiology isn’t well understood. Specific accomplishments here will include identifying both predictive and prognostic biomarkers as well as finding ways to quantify disease progression and achieve translation of basic science.
  • The second main focus area is to increase patient access to investigational new drugs “through greater participation in clinical trials.” The agency plans to expand use of digital health technologies and decentralized trial designs “to facilitate the collection of data from participants where they live.” Expanded access to investigational drugs should also be “appropriately integrated into development programs,” according to the strategy.
  • Third, the FDA plans to enhance the infrastructure for clinical trials and make the trial process more agile through “rethinking approaches to clinical trials can enable early selection of promising therapeutic candidates for further development, optimize clinical trial design, improve access to the trials, streamline clinical trial operations, and reduce the time and cost of drug development,” according to the plan.
  • In addition to the establishment of an ALS task force in FY 2022, the agency also intends to support research into specifics of the natural history and pathophysiology of ALS, as well as developing animal models and other models that “may be most useful for pharmacological pre-clinical proof of concept.” The FDA further plans to support efforts in biomarker development and validation, including identifying candidates for surrogate endpoints, along with other near-term goals.
  • Medium-range goals for the ALS science strategy will be accomplished in FY 2023 and 2024 to include exploring gaps in what’s known about the natural history of ALS and facilitating more data sharing and standardization through existing agency and external resources.
  • ALS is a fast-moving, irreversible and fatal neurodegenerative disease. For most patients, symptoms appear in later middle age, with death coming just 3 or 4 years after the first symptoms appear. Diagnosis is often delayed, so the time from diagnosis to death may be as little as 2 years, leaving a short window for therapeutic intervention. ALS is rare, with a prevalence of about 6 per 100,000 in the U.S.; though some cases are familial and associated with known genetic mutations, many cases are sporadic.
  • There are two FDA-approved therapies for ALS, but neither does more than keep some symptoms at bay for a time and extend life by a few months, at best. A third investigational therapy, AMX0035, recently received a favorable vote from the FDA’s Peripheral and Central Nervous System Advisory Committee, which was reconvened for an unusual second meeting after Amylyx, the sponsor of AMX0035, submitted additional post hoc data analyses over the summer. ALS has indisputable unmet need and a vigorous advocacy community. The PDUFA target date for the therapy is September 29, 2022. [Read AgencyIQ’s analyses of the two advisory committee meetings here and here, and POLITICO’s reporting on the involvement of ALS patient-advocates in drafting the ACT for ALS bill here.]

Now, the FDA and NIH have announced their partnership with the Critical Path Institute to move the rare neurodegenerative disease strategy forward

  • Earlier in 2022, the FDA announced plans to establish a formal public-private partnership with the National Institutes of Health (NIH) and “one or more other eligible entities for the purpose of advancing the understanding of and fostering the development of treatments” for the target set of diseases. Among the goals will be advancing drug development tools.
  • Today, the partnership was announced by three participating entities, with the Critical Path Institute (C-Path) launching a website. The webpage sets forth the basics of the remit for the partnership and identifies key C-Path staff for the effort, which will also include representatives from FDA and NIH.
  • C-Path, the convenor for the public-private partnership, is a nonprofit that was launched under the FDA’s Critical Path Initiative program in 2005; just over half of its funding comes from Federal sources, including the FDA. The organization “provides the legal and scientific infrastructure to create a uniquely neutral environment for industry, academia, regulators and other government agencies, to work together to accelerate and de-risk the medical product development process,” according to the C-Path website. Through consensus-building and the participation of regulators, C-Path supports the generation of “the necessary confidence to assure the adoption of the medical product development solutions by sponsors and regulators.”
  • The new Critical Path for Rare Neurodegenerative Diseases (CP-RND) will convene experts in ALS and other rare neurodegenerative diseases while also bringing in patients, advocacy groups and private entities. C-Path describes its development atmosphere as a “safe harbor for commercial drug developers to bring data and shared learnings.”
  • The FDA’s focus within the CP-RND will be on accelerating therapeutic innovation and building regulatory science around RNDs, while the NIH will concentrate on preclinical and clinical discovery and translation in the field.
  • The Rare Disease Cures Accelerator-Data and Analytics Platform (RDCA-DAP) will play a role in bringing patient data from disparate sources into the development process. The platform houses, maps, standardizes, and curates dat, which is then made available via a secure cloud interface for C-Path research participants and other users.

What’s next?

  • The three main objectives of the CP-RND will be to establish the “transformative” public-private partnership, to “develop an individual and experiment-level integrated database,” and to “generate actional solutions that can tangibly accelerate drug development.”
  • One task the FDA had committed to finishing by the end of FY 2022 is to establish an FDA Rare Neurodegenerative Diseases Task Force, as directed by the ACT for ALS. Building on the resources of the recently established Accelerating Rare disease Cures (ARC) Program, the task force “will ensure a strategic cross-cutting Agency approach” in developing rare neurodegenerative disease medical products, according to the plan.
  • Today’s establishment of the public-private partnership with NIH and C-Path does not appear include naming of a task force, and the FDA’s homepage for the ACT for ALS initiative doesn’t have any further information. AgencyIQ will provide an update on whether the FDA meets its deadline for naming task force members.
  • As the FDA points out in its action plan, “consistent funding” will be the only way these ambitious goals will be accomplished. Some of the necessary resources the agency highlights for the ALS strategy alone include cross-disciplinary subject matter experts, funding for “exploratory research projects,” and program staff for all the planned activities.
  • Entities interested in participating in the CP-RND work should reach out to C-Path at [email protected].

To contact the author of this piece, please email Kari Oakes ( [email protected])
To contact the editor of this piece, please email Laura DiAngelo ( [email protected])


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