Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required)

The National Institute of Neurological Disorders and Stroke (NINDS), in collaboration with the Office of the Director at the National Institutes of Health (NIH), has announced a forecasted Notice of Funding Opportunity (NOFO) titled Amyotrophic Lateral Sclerosis (ALS) Intermediate Patient Population Expanded Access (U01 Clinical Trial Required). This program is part of the U.S. Department of Health and Human Services’ ongoing efforts to advance scientific research and treatment development for ALS, a rapidly progressive and ultimately fatal neurodegenerative disease. The announcement is intended to provide researchers and institutions with early notification to allow adequate time to prepare proposals and collaborations. ALS is a severe and life-threatening disease characterized by progressive muscle weakness and wasting, with a mean survival of only three to five years after symptom onset. Currently available treatments provide limited benefits, and no therapies exist that can halt or reverse disease progression. While some ALS patients may qualify for ongoing phase 3 clinical trials, many are excluded due to restrictive eligibility criteria designed to optimize trial efficiency. As a result, a substantial number of individuals with ALS cannot access investigational treatments through traditional clinical trial mechanisms. This NOFO aims to address this gap by supporting expanded access (EA) protocols for investigational drugs and biological products targeting intermediate-sized ALS patient populations who are otherwise ineligible for clinical trials. Expanded access programs are regulated by the U.S. Food and Drug Administration (FDA) under section 561 of the Federal Food, Drug, and Cosmetic Act and allow patients with life-threatening conditions to receive investigational medical products outside of clinical trials. Section 2 of the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS, P.L. 117-79) established a grant program specifically to support scientific research using data derived from EA protocols for ALS. This initiative will allow researchers to leverage data from patients treated under EA to inform the development of therapies for prevention, diagnosis, mitigation, treatment, or cure of ALS. The funding instrument will be a cooperative agreement under the U01 activity code, with NIH anticipating making four awards. The total estimated program funding is $40,000,000. No cost sharing or matching is required. Applications are expected to open on October 29, 2025, with a submission deadline of November 28, 2025. Awards are anticipated to be announced on September 1, 2026, with project start dates aligning with that same day. While this announcement is forecasted, investigators with expertise in ALS research are strongly encouraged to begin developing collaborations and project concepts. Eligibility is open to a wide range of entities including state and local governments, tribal governments and organizations, nonprofits with or without 501(c)(3) status, institutions of higher education, for-profit organizations, small businesses, school districts, and public housing authorities. Importantly, eligible applicants must be clinical trial sites engaged in a phase 2/3 or phase 3 efficacy trial supported by a small business concern that is the FDA-designated sponsor of a drug or biological product under an active Investigational New Drug application for ALS. For further information, the grantor contact is Amy Tsou, MD, MSc, who may be reached at (240) 987-2815 or by email at amy.tsou@nih.gov. At this stage, applications are not being solicited. The publication of this forecasted NOFO is designed to ensure that interested applicants have sufficient time to prepare meaningful and competitive proposals once the funding opportunity officially opens.