On October 28, the FDA held a public meeting to hear from the rare-disease community as it develops a new framework for reviewing rare-disease treatments. The Foundation to Fight H-ABC attended through its CEO and Co-Founder, Michele Sloan, representing the patient community.
The discussion matters because the usual path to treatment development does not always fit diseases with very small patient populations, limited natural-history information, or treatments that differ from one another. FDA is considering how its review can account for those realities while maintaining its standards for safety and effectiveness. The framework is still being developed; the meeting was an opportunity to help shape it, not an announcement of a new approval pathway.
What FDA is asking the community
FDA asked for specific input in four areas: how to review a treatment using evidence that can realistically be generated for a particular disease and patient population; how to make requirements clearer and more consistent; how patients, disease experts, and researchers can inform review decisions; and how manufacturing and product-quality expectations should work for rare-disease therapies.
Patient experience is relevant to those questions. Patients and caregivers can explain which changes matter in daily life, what makes study participation difficult, and how a disease affects people at different ages and stages. That information can help sponsors and regulators choose outcomes, plan studies, and weigh potential benefits and risks. FDA says it wants patient perspectives early in development and at defined points during review, not only after a study has been designed.
The request is also practical: describe the problem, explain who it affects, and suggest a change FDA could consider. A personal experience can show why a problem matters; a clear recommendation can help the agency decide what to do about it.
What advocate leaders are emphasizing
NORD welcomed FDA’s initiative and said that tailoring how evidence is evaluated to rare-disease realities should not mean lowering standards. Its response also pointed to the work ahead: consistent implementation, adequate staffing, and sustained leadership. After the October 28 meeting, NORD reported hearing recurring calls for a stronger patient voice, clearer and more consistent expectations, and evidence requirements that are reasonable for the question being studied.
In a November 2 reflection, RARE Foundation’s James Valentine urged advocates to bring solutions as well as examples of what is not working. He raised questions about how patient perspectives should inform decisions, how lessons from ultra-rare diseases might apply more broadly, and how the framework can remain transparent and consistent.
The message is clear: the community wants FDA to follow through with specific, usable processes. The framework’s value will depend on what changes in the way treatments are developed and reviewed.
The longer-term framework: what patient advocates are asking FDA to build
The recommendations in this section go beyond the brief oral comments Ms. Sloan delivered at the October 28 meeting on behalf of the Foundation. Those comments focused on three immediate H-ABC needs: a path from individual-patient ASO treatment toward a study that can serve more patients, inclusion of older patients, and access to natural-history data. The ideas below offer a broader, longer-term view of what a rare-disease framework should provide across programs. They are the Foundation’s advocacy recommendations, not policies FDA has adopted. They remain pertinent to families now because the barriers they address are already affecting treatment development; work on the larger framework should not push those needs aside.
The FDA’s white paper sets out goals and lists changes the agency may consider. It does not yet give families or developers a working pathway. From the Foundation’s patient advocacy standpoint, FDA should be pressed to take practical steps that address the barriers patients face.
A written plan early in development. Patient advocates should ask FDA to establish an early, cross-center discussion that brings the right reviewers together with a sponsor and, when useful, disease experts and patient representatives. That discussion should produce a written plan identifying the evidence available, the questions that remain, the study approaches FDA considers reasonable, the manufacturing issues to resolve, and the milestones for the next decisions. Families and developers need to know what FDA is asking for and what would support moving forward. Clear written advice could also reduce conflicting answers across review divisions.
A way to move from individual treatment to a study that can serve more patients. When a therapy has already been given to several patients and others are waiting, patient advocates should ask FDA to explain how existing treatment experience can inform the next step. The framework should describe how a sponsor could organize information on exposure, dosing, safety, follow-up, outcomes, and biomarkers, then propose a prospective shared protocol with common data collection, staged enrollment, and independent safety oversight. FDA should identify what findings would support continuing, pausing, or expanding enrollment. Individual-patient experience alone cannot establish that a treatment works, but families should not have to accept that each experience stays isolated with no clear route toward broader study.
Guidance on what evidence can be combined and what it can establish. Patient advocates should ask FDA to help sponsors evaluate evidence sources that may be available in small populations: natural-history data, clinical measures, biomarkers, mechanistic findings, prospective treatment experience, and real-world information. The guidance should explain the strengths and limitations of each and how they may contribute to a decision. When a conventional controlled trial is feasible and informative, it should be considered. When it is not, FDA should help sponsors assess alternatives such as external comparators, adaptive or platform trials, and Bayesian methods, including the assumptions and safeguards needed. This would make “fit for purpose” a concrete scientific discussion rather than a case-by-case plea for flexibility.
Patient input belongs in that discussion. Patients and caregivers can identify meaningful outcomes, study burdens, and the trade-offs that matter to them. They should also be asked how they view uncertainty about treatment benefit in light of the disease and available options. That perspective can inform development and benefit-risk discussions; it does not replace evidence of safety and effectiveness.
A workable process for using natural-history data that already exists. Patient advocates should ask FDA to convene NIH, hospitals, researchers, and patient organizations around standard data dictionaries, request procedures, response timelines, transparent cost estimates, reusable agreements, and secure analysis options. The process should protect consent and privacy while recognizing investigators’ contributions. FDA cannot require every institution to release its data, but it can help bring the parties together and make data access a visible part of rare-disease trial planning. Families should not be asked to repeat burdensome assessments simply because existing information is difficult to find or use.
A plan for older patients and different disease stages. Patient advocates should ask FDA to expect sponsors to explain age and disease-stage exclusions, state what evidence would allow those patients to participate, and set a timeline for reconsidering them. Trial measures should capture stabilization as well as improvement and account for mobility, communication, and caregiver needs. If an older or more advanced group cannot enter at the beginning, there should be a clear reason and a plan for when it will be addressed.
Early, product-specific manufacturing advice and public accountability. Patient advocates should ask FDA to clarify manufacturing and quality expectations before they become late barriers: which controls are essential at each stage, what must be resolved before a study or expansion, and what can be addressed as production scales. The quality and safety protections remain central; the requirements and timing should reflect the product and its risks. FDA should also report whether the framework is improving cross-center consistency, producing clearer written advice, increasing inclusion across ages and stages, and reducing avoidable duplication in data collection. Speed alone is not enough to show that patients are better served.
For the Foundation, the test is whether a family or clinician can see a credible next step: what evidence is needed, how existing knowledge can be used, when more patients might enter a study, and how FDA will make the next decision. That is the longer-term framework the Foundation believes patient advocates should ask FDA to build. The immediate barriers raised at the meeting remain in front of patients and families now.
The Foundation’s comments to FDA
The Foundation brought three issues from its work in H-ABC/TUBB4A and across the rare-disease community.
Moving from individual treatment toward broader development. In TUBB4A, several children have received an antisense oligonucleotide through individual-patient protocols, and more families are waiting. The Foundation asked FDA to define a product-specific path for moving from individual treatment experiences to a structured, closely monitored development program. Developers and clinicians need to know what evidence FDA will consider, what additional information is needed, and what milestones could support expanding enrollment. The objective is to build evidence and move toward treatment for all eligible patients, with appropriate safeguards.
Including older patients and people at different disease stages. Older children and adults should not be left out simply because their disease is more advanced or study participation is more complicated. If a group cannot be included at the outset, the reason should be clear, along with a plan for when and how it will be studied. Trial measures should be able to capture stabilization or meaningful change at different stages. Study visits should also account for mobility, communication, and caregiver needs.
Making natural-history data usable. Families should not be asked to repeat burdensome data collection when relevant information already exists. Yet access to institutionally held natural-history data can be costly and unpredictable, creating a barrier for small developers planning a trial. The Foundation urged FDA to work with NIH, institutions, investigators, patient organizations, and developers on a practical process: clear requests and timelines, reasonable and transparent costs, privacy protections, consistent data standards, and appropriate credit for the people who built the resource.
The Foundation expanded on these recommendations in supplemental comments after the meeting, including shared protocols, staged enrollment, common data collection, and clearer data-use processes. It also raised the outcome families ultimately need: an approved treatment they can obtain and afford. FDA does not make insurance coverage decisions, but evidence developed for FDA review can affect later coverage discussions. Coordination with CMS and other payer stakeholders should be part of the broader conversation.
The public comment period is open through December 11, 2026, under Docket No. FDA-2026-N-12214. Patients, caregivers, clinicians, researchers, and developers can still contribute. The longer-term framework matters, but families also need attention to the immediate barriers raised at the meeting. The Foundation’s comments ask FDA to keep both in view: build a clearer process for rare-disease development and address the H-ABC challenges that are already affecting patients waiting for treatment.