The ALS Association is deeply committed to accelerating the development of novel ALS therapies and ensuring they are accessible to those who need them. The Association is announcing today its latest strategic action with the release of Principles for Urgent, Patient-Centered ALS Clinical Trials: a series of recommendations to clinical trial sponsors and regulatory bodies worldwide.
The Principles set out a clear framework for the design and conduct of ALS clinical trials that are efficient, impactful, and respectful. We view them as essential to both maximize the participation of people with ALS and their caregivers and to ensure every available tool is used to streamline drug development and regulatory-review processes. Regardless of the detailed specifics that may arise from FDA guidelines in the next few weeks, we hope these principles can help focus trial sponsors and regulators on the most important aspects of trial design and lead to ever-improving clinical trials as our fight against ALS advances.
The Principles also are built on a series of critical steps taken by the ALS community to fundamentally improve the way in which our research and regulatory stakeholders approach trial design. The Association has engaged leading technical experts, people with ALS, and their caregivers in each of these initiatives. This work, summarized below, includes landmark ALS community-led drug development guidance, updated clinical trials guidelines, and a national workshop to inform the draft FDA ALS drug development guidance.
ALS Community Drug Development Guidance
The Association identified the lack of an FDA guidance as a critical gap in the ALS therapy development system. That gap produced regulatory uncertainty and discouraged companies from entering the field. For only the second time in history, a disease-specific community took up the challenge to produce a draft guidance to immediately inform both industry and regulators, as the FDA committed to move forward, as well. Over 100 clinical, research, and policy experts, as well as a Patient and Caregiver Advisory Committee, convened to produce the Drug Development Amyotrophic Lateral Sclerosis: Guidance for Industry. This effort clearly demonstrated the community’s demand for novel, flexible approaches to ALS therapy development.
ALS Clinical Trial Guidelines
Concurrent and in coordination with the community-led drug development guidance, The ALS Association invested in a fundamental update of the 1999 Airlie House guidelines for the design and implementation of preclinical therapeutic studies and clinical trials in ALS. More than 140 experts from around the world launched this work at a second Airlie House conference leading to consensus around critical aspects of developing effective ALS therapies. The updated Guidelines address nine key areas of need within ALS clinical trials, including: (1) preclinical studies, (2) biological and phenotypic variation in ALS, (3) outcome measures, (4) disease-modifying and symptomatic interventions, (5) recruitment and retention, (6) biomarkers, (7) clinical trial phases, (8) beyond traditional trial designs, and (9) statistical considerations.
ALS Community Workshop: Therapy Development and Regulatory Pathways
Shortly after the release of the FDA’s draft ALS drug development guidance, The ALS Association organized a national workshop to engage patients, caregivers, clinicians, and researchers in developing critical analysis and comment on the agency’s document. The extensive knowledge and insight in both the community-led guidance and consensus guideline projects informed this discussion with FDA leaders. Following the workshop, the Association collaborated with community leaders to produce specific recommendations for the FDA to incorporate in a finalized ALS drug development guidance.
Taken together, these initiatives represent tangible work to reduce the time and resources required to bring new therapies to people with ALS. We know they are already making a difference through reports both from industry and regulators. Many in our community were gathered at our 2017 Advocacy Conference when Dr. Janet Woodcock from FDA observed that the work of the Association and our partners significantly supported the agency’s ability to approve the second ALS-indicated therapy in an extraordinarily timely and efficient way.
But this clearly is not enough. Our previous work has been exhaustive and technical. We took the workshop findings and FDA guideline recommendations and distilled them into Principles for Urgent Patient-Centered Clinical Trials. We hope this higher-level document will help everyone – regulators, trials sponsors, scientists, and potential trial participants – incorporate what is most important about clinical trial design for ALS into their thinking, and into better clinical trials in the future. We invite all who share this commitment to join us in ensuring that the Principles become reality with our research, development, regulatory, and care partners.