As the grandfather of a girl with a rare disease, I’ve learned that for families like ours, hope often comes not as a cure, but as a clinical trial: carefully designed but inevitably exclusive.
My granddaughter Anna has Dravet syndrome, a catastrophic childhood epilepsy most often caused by mutations in the SCN1A gene. Like many children with Dravet, she has endured hundreds of seizures, even though she is taking multiple anti-seizure medications approved by the Food and Drug Administration, though most are prescribed off-label for Dravet. Over time, her parents have been forced to navigate the uncomfortable space between standard care and experimentation, weighing the risks to their daughter against the relentless damage caused by her ongoing seizures.
That agonizing journey pushed me far beyond the role of grandfather and a fundraiser and supporter for the Dravet Syndrome Foundation. I began studying the science behind emerging therapies, engaging with clinicians, researchers, and biotechnology companies, and advocating for greater access to investigational treatments for children who have exhausted approved options. After more than 40 years working in health care companies, I understand clinical trial design, regulatory constraints, and the very real pressures small drug developers face.
In that work, I encountered a sobering truth: Even when promising therapies exist, and even when the FDA is willing to authorize expanded access, families like ours are often left without a path forward — not because of safety concerns, but because a child does not fit the protocol.
That reality confronts many families affected by Dravet syndrome today. Despite recent progress and several FDA-approved therapies, many children with Dravet still endure frequent seizures and profound developmental disabilities.
Investigational therapies offer real promise. Yet for many patients — including my granddaughter — access to those therapies remains out of reach because they fall outside clinical trial eligibility criteria such as age or current medications.
This is where the system breaks down.
The U.S. has a well-established legal pathway for expanded access, often referred to as compassionate use. Contrary to common perception, the FDA is rarely the barrier. The agency authorizes more than 99% of expanded-access requests it receives, typically within days.
Instead, decisions rest with drug companies.
Companies developing therapies for rare diseases frequently decline compassionate use requests not out of indifference, but out of rational business and regulatory concern. These concerns often include potential risk to ongoing or future clinical trials; fear that adverse events could complicate regulatory review; limited manufacturing capacity, particularly for biologics and gene therapies; and resource constraints within small or mid-size biotech companies.
These concerns are legitimate. But the consequence is a paradox: Patients with the greatest unmet need — those excluded from trials — are the least likely to gain access to promising therapies.
Dravet syndrome illustrates this gap vividly. Recently, attempts to wean Anna off of cenobamate so she could qualify for Stoke Therapeutics EMPEROR gene therapy trial failed because she had more seizures. Yet being on the drug excludes her from the trial, and the company is not willing to support compassionate use access.
Children who have exhausted approved therapies may respond meaningfully to investigational approaches such as antisense oligonucleotides, gene-regulation strategies, or gene therapies, two of which are now advancing through human clinical trials. Yet many patients are excluded from trials due to age cutoffs or prior or current exposure to medications.
Families are told, implicitly or explicitly, to wait for approval, for another trial, for something else. For children with severe neurodevelopmental disorders, time is not neutral. Ongoing seizures and developmental regression are cumulative and often irreversible.
Mandating compassionate use is unlikely to succeed and could inadvertently slow innovation, particularly for small biotechnology companies operating with limited capital, staff, and manufacturing infrastructure.
But well-designed incentives could change sponsor behavior without coercion. Congress and the FDA could create incentives like these:
- Limited priority review extensions or expedited review of future applications for sponsors who implement structured expanded-access programs.
- Liability and regulatory safe harbors, clarifying that adverse events occurring under FDA-authorized expanded access will not be weighed against sponsors during benefit–risk evaluation.
- Data firewalls, ensuring that real-world data from compassionate use is excluded from pivotal efficacy analyses unless sponsors choose otherwise.
- Tax credits or targeted grants to offset manufacturing and administrative costs associated with expanded access in rare diseases.
- Public recognition, highlighting companies that responsibly offer expanded access as ethical leaders in rare-disease drug development.
None of these measures would lower FDA approval standards. None would compel companies to act against their interests. All would encourage a culture in which compassion and innovation coexist.
Rare-disease drug development depends on public trust: trust from caregivers, clinicians, and advocates who participate in trials, share data, and champion innovation. When families see that investigational therapies exist but are categorically unavailable to those who do not “fit the protocol,” that trust erodes.
Incentivizing compassionate use is not about undermining science. It is about recognizing that ethical leadership in rare-disease drug development includes responsibility to those left behind by trial design.
Dravet syndrome is just one example. The same dilemma plays out across hundreds of rare pediatric diseases.
If we truly believe that patients come first, then we must build a system where hope is not confined by inclusion criteria and where companies are supported, not punished, for choosing compassion.
