When the FDA announces it will not approve a potential treatment, the decision can feel final to the people living with the disease in question. For patients with rare conditions, regulatory language often arrives without much explanation, leaving families to wonder whether a door has closed or whether the conversation is still ongoing.
That uncertainty surfaced again after the FDA issued a Complete Response Letter for troriluzole, a drug being studied as a potential treatment for spinocerebellar ataxia (SCA), a rare and progressive neurological disease. For patients and caregivers who have followed the drug’s development closely, the recent decision raised urgent questions about time, access, and what happens next. Those benefiting from the investigational drug as part of a compassionate use program wonder if they will continue to have access.
What the FDA’s Decision Actually Means
A Complete Response Letter, or CRL, means the FDA cannot approve a drug application in its current form. It does not mean the drug has been permanently rejected or that development must stop. Instead, it signals that the agency believes additional evidence or analysis is needed before approval can be considered.
In this case, the FDA did not dispute that SCA is a serious disease with no FDA-approved treatments, nor did it question the unmet medical need. There was not any controversy whether the real-world evidence study submitted in the FDA filing achieved statistical significance on the study’s primary outcome. The decision focused on whether the study design and evidence package met the FDA’s current standards for “an adequate and well-controlled study” to demonstrate effectiveness, a definition that can vary in its interpretation between reviewers or divisions at the FDA.
But for patients, the distinction between “not approved yet” and “not approved” can feel largely academic. There is also uncertainty around how long a company will continue efforts with ambiguous and shifting regulatory standards for rare disease approvals. In this case, the company studying SCA has been running trials and interacting with the FDA for over eight years.
Why Evidence Looks Different in Rare Diseases
Spinocerebellar ataxia affects balance, coordination, speech, and independence. Over time, many people with SCA experience irreversible loss of function. Because the disease is rare, slowly progressive over years and highly variable, large randomized clinical trials can be difficult or impractical to conduct.
As a result, drug developers working in rare diseases often rely on alternative approaches, including natural history studies, externally controlled comparisons, and real-world data. These methods aim to show whether a treatment slows disease progression compared to what would otherwise be expected.
The FDA has acknowledged these challenges publicly. In recent guidance and policy initiatives, the agency has said that rare diseases “often cannot feasibly be studied using traditional randomized controlled trials,” and that non-traditional sources of evidence may be considered when appropriate. At the same time, the FDA has emphasized that such data must still be reliable and interpretable, and that concerns about bias and study design are evaluated on a case-by-case basis.
Why Timing Feels Different to Patients
For people living with progressive neurological diseases, delays carry a particular weight. Skills lost to disease progression cannot be regained, and waiting can feel like an active cost rather than a neutral pause.
Advocacy organizations have emphasized that urgency is not abstract for families affected by SCA. As part of this process, the National Ataxia Foundation surveyed its community to better understand patient and caregiver perspectives. More than 3,000 people responded.
The absence of any approved treatments for SCA clearly weighed heavily on the respondents. In that survey, 97 percent said they agreed that the FDA should apply regulatory flexibility and accept the New Drug Application for troriluzole for a full review.
In public statements, NAF has described regulatory delays as carrying “a unique cost in progressive rare diseases,” noting that patients understand uncertainty but are acutely aware that time lost to disease progression cannot be recovered. The organization has repeatedly emphasized that members of the ataxia community are willing to engage with risk and ambiguity if it means a chance to slow decline.
The survey included more than 75 pages of quotes from those affected, including these:
You’re taking away an opportunity for someone with a debilitating disease without giving it a chance. That’s just unfair. Please reconsider.
I am a patient living with SCA3. I feel if there’s any opportunity at making people live longer or with less symptom progression, they should be offered that opportunity.
This is a progressive disease with no treatment or cure at present. Most sufferers would be happy to try a new treatment, including me.
How This Fits Into a Broader FDA Conversation
The decision on troriluzole comes amid a broader conversation at the FDA about how rare disease treatments should be evaluated. In recent years, the agency has introduced initiatives such as its Rare Disease Evidence Principles, aimed at providing clearer guidance on how evidence may be generated and assessed when traditional trials are not feasible.
FDA leadership has described these efforts as an attempt to take a “flexible, common-sense approach” within existing regulatory authority, while maintaining standards intended to ensure that approved treatments are supported by credible evidence. The agency has also emphasized that flexibility does not remove the need for convincing data, particularly when real-world or externally controlled evidence is used.
The FDA has approved treatments for other rare, degenerative conditions using non-traditional evidence packages, underscoring that flexibility is possible but highly variable and context-specific. Those suffering from SCA wait for a first treatment while hearing the promise of new leadership rolling back “red tape” and speeding up new therapies.
For now, the next steps remain under discussion. The FDA has a process for appeals or other engagement with the drug’s developer, Biohaven, and advocacy organizations have said they plan to stay involved as those conversations continue. Whether and when the application returns for review is not yet clear. For patients living with SCA and their families, that uncertainty is difficult. Many say they are watching closely, waiting for clarity about what comes next and how much time they may have.