Stronger Together: NORD’s Congressional Briefing on the Heels of FDA’s “Plausible Mechanism” Draft Guidance

As rare disease week gets underway, Goodwin was proud to attend the Congressional briefing held by the National Organization for Rare Disorders (NORD), “Patient Advocacy Driving Innovation for People Living with Rare Diseases.” One take-home message following the congressional briefing was clear: patient advocacy is not tangential to innovation — it is foundational. With thirty million Americans living with a rare disease, fewer than 5% of the more than 10,000 known rare diseases have a treatment approved by the U.S. Food and Drug Administration (FDA). Urgent priorities discussed during the briefing included accelerating research and improving access to knowledgeable healthcare providers, diagnostics, clinical trials, and therapies. Across panels, speakers emphasized that advocacy organizations are helping build the infrastructure that makes innovation possible — from natural history studies and patient registries to narrowing-down meaningful clinical trial endpoints.

Several speakers shared deeply personal journeys that underscored how policy and science intersect with lived experience. Theresa Strong, PhD, representing the Prader-Willi Research Foundation, described how the Foundation helped drive therapy development by convening stakeholders and de-risking research. Rohini Kosoglu, Venture Partner at Fusion Fund, reflected on her shift in perspective from her experience in the legislative and executive branch involved in various healthcare developments to becoming a rare disease parent, highlighting the power of personal storytelling in influencing legislation and advocacy. Ada Homosh, MD, of Johns Hopkins Medicine and the NORD Rare Disease Center of Excellence stressed the need for improved clinician awareness, stronger newborn screening programs, and improved coding systems for rare diseases. Several stakeholders, including NORD, have agreed that specific ICD codes are pivotal in allowing researchers and physicians to track how many individuals are impacted by a specific disease, which is vital for rare diseases which often lack validated disease prevalence or incidence estimates. 

Ultimately, the briefing reinforced that rare disease policy is not partisan — it is a national priority. From expanding newborn screening and strengthening the National Institutes of Health funding to modernizing regulatory pathways at FDA and improving access to genetic counseling and medical foods, stakeholders noted that sustained partnership between patients, advocates, researchers, developers, regulators, and lawmakers will be essential. As emphasized throughout the event, access for rare disease stakeholders is the ultimate outcome — and advocacy continues to be one of the most powerful drivers of progress.

We note that the briefing came one day after the draft guidance release of draft guidance on the use of its “plausible mechanism” framework for certain rare disease drugs. While the guidance focuses on individualized genomic editing and antisense oligonucleotides in large part, the FDA notes that general concepts of the guidance may apply to other types of therapies. Under this framework, a single trial may provide a basis for approval with confirmatory nonclinical or clinical evidence, including mechanistic or pharmacodynamic data, confirmation of target engagement, and exposure-response on biomarkers and clinical outcomes. The draft guidance also discusses flexibility in the nonclinical program for qualifying therapies and recommends discussion with FDA on manufacturing plans and preparation of supporting data. Finally, the draft guidance underscores FDA’s expectations on safety assessments and monitoring for unexpected or delayed adverse events. The comment period is open for 60 days and on Monday, Secretary Kennedy and Commissioner Makary both expressed strong support for the plausible mechanism pathway and its ability to accelerate cures for rare disease patients.