For families navigating the complexities of rare diseases, the promise of a new therapy often arrives with a frustrating caveat: clinical trials, while carefully designed, are inherently exclusive. Access to potentially life-altering treatments isn’t guaranteed by need, but by strict adherence to eligibility criteria.
This reality is acutely felt by Theron Odlaug, whose granddaughter Anna lives with Dravet syndrome, a severe form of childhood epilepsy often caused by mutations in the SCN1A gene. Despite being on multiple FDA-approved anti-seizure medications – many used “off-label” for Dravet – Anna continues to experience frequent seizures and developmental challenges. Odlaug’s personal experience has propelled him to advocate for greater access to investigational treatments for children who have exhausted approved options.
The challenge isn’t a lack of willingness from the Food and Drug Administration (FDA). In fact, the FDA authorizes over 99% of expanded access requests, often within days. Expanded access, also known as compassionate use, allows patients with serious conditions to access investigational therapies outside of clinical trials. However, the ultimate decision rests with the pharmaceutical companies developing these therapies.
Companies face legitimate concerns. Allowing broader access to investigational drugs could potentially jeopardize ongoing clinical trials, complicate the regulatory review process if adverse events occur, strain limited manufacturing capacity – particularly for complex therapies like gene therapies – and overwhelm the resources of smaller biotechnology firms. These concerns are particularly acute in the realm of rare diseases, where patient populations are small and the financial stakes are high.
The result is a paradox: the patients with the greatest unmet need – those who don’t qualify for trials – are often the least likely to access promising new therapies. Odlaug’s granddaughter, Anna, exemplifies this dilemma. Recent attempts to wean her off cenobamate, a medication she currently takes, to qualify for a gene therapy trial by Stoke Therapeutics were unsuccessful due to increased seizure activity. However, remaining on cenobamate disqualifies her from the trial and the company is currently unwilling to consider compassionate use access.
This situation isn’t unique to Dravet syndrome. Children with severe neurodevelopmental disorders face a ticking clock. Ongoing seizures and developmental delays can lead to cumulative and often irreversible damage, making timely access to treatment critical. Waiting for trial completion or future opportunities may simply be too late.
Mandating compassionate use isn’t a viable solution, Odlaug argues, as it could stifle innovation, particularly for small biotech companies operating with limited resources. Instead, he proposes a system of incentives designed to encourage companies to implement structured expanded-access programs without coercion.
Several potential incentives could be considered by Congress and the FDA. These include limited priority review extensions or expedited review of future applications for companies that offer expanded access; liability and regulatory safe harbors clarifying that adverse events occurring under FDA-authorized expanded access won’t negatively impact future regulatory evaluations; data firewalls to ensure real-world data from compassionate use isn’t used against sponsors in pivotal efficacy analyses unless they choose to include it; tax credits or targeted grants to offset manufacturing and administrative costs; and public recognition for companies demonstrating ethical leadership in rare disease drug development.
These incentives wouldn’t lower FDA approval standards or force companies to act against their interests. Rather, they would foster a culture where compassion and innovation coexist. Maintaining public trust is paramount. Rare disease drug development relies on the participation of patients, clinicians, and advocates in trials and data sharing. When families perceive that investigational therapies are available but inaccessible due to restrictive eligibility criteria, that trust erodes.
Incentivizing compassionate use isn’t about compromising scientific rigor; it’s about acknowledging a responsibility to those who fall outside the boundaries of traditional trial design. The challenges faced by families affected by Dravet syndrome are mirrored across hundreds of other rare pediatric diseases. If patient well-being is truly the priority, a system must be built where hope isn’t limited by protocol requirements and where companies are supported, not penalized, for choosing compassion.
Theron (Ted) Odlaug worked in health care leadership for over 40 years before becoming an advocate for rare disease access. He is an operating partner at Signet Healthcare Partners, which provides growth capital to health care companies.
