Advocating for Access: The Challenge of Rare Disease Trials

Families affected by rare diseases often find hope in clinical trials, but these trials frequently exclude patients with specific conditions. This has been the reality for families like that of Anna, a young girl diagnosed with Dravet syndrome, a severe childhood epilepsy typically linked to mutations in the SCN1A gene. Her grandfather, Theron (Ted) Odlaug, has become an advocate for greater access to investigational treatments, highlighting the challenges faced by families navigating the complexities of clinical trials.

Anna has endured countless seizures despite being prescribed multiple anti-seizure medications approved by the Food and Drug Administration (FDA). Many of these medications are used off-label for Dravet syndrome. Her parents have found themselves in a difficult position, weighing the risks of standard care against the ongoing damage caused by her seizures. This situation compelled Odlaug to move beyond his role as a grandfather and advocate for the Dravet Syndrome Foundation, delving deeply into the science of emerging therapies and engaging with a range of stakeholders, from clinicians to biotechnology companies.

Through his extensive experience in healthcare, Odlaug discovered a concerning truth: even when promising therapies are available, families like his often remain without options due to strict clinical trial eligibility criteria. The current system tends to prioritize trial protocols over the urgent needs of patients, particularly children like Anna who suffer from Dravet syndrome. Despite recent advancements and FDA-approved therapies, many children continue to experience severe seizures and significant developmental challenges.

Investigation into investigational therapies reveals a stark contrast between potential and accessibility. While therapies such as antisense oligonucleotides and gene therapies show promise, many children are excluded from trials because they do not meet specific age requirements or have prior exposure to certain medications. This exclusion not only delays potential treatment but also exacerbates the conditions of children who cannot wait for new trials or approvals.

The issue is further complicated by the concept of compassionate use, which is a legal pathway in the U.S. allowing patients to access experimental treatments outside of clinical trials. Contrary to popular belief, the FDA is not typically a barrier to compassionate use; it approves over 99% of requests within days. Instead, the responsibility often falls on pharmaceutical companies, which may decline compassionate use requests due to valid business and regulatory concerns. These concerns can include the risk to ongoing clinical trials, potential complications during regulatory reviews, and limitations in manufacturing capacity.

The paradox is clear: those who need access the most—patients excluded from clinical trials—are often the least likely to obtain it. For instance, Odlaug’s granddaughter was unable to qualify for the EMPEROR gene therapy trial by Stoke Therapeutics due to her ongoing seizures, which were exacerbated by her current medication. Despite the potential benefits of investigational therapies, children like Anna remain caught in a cycle of exclusion.

In light of this pressing situation, Odlaug proposes the implementation of well-designed incentives to encourage pharmaceutical companies to consider compassionate use more favorably. He emphasizes that such measures would not compromise FDA approval standards or force companies to act against their interests. Instead, they would foster an environment where compassion and innovation can coexist, ultimately benefiting both patients and drug developers.

Building trust is essential for the development of rare disease drugs. When families see investigational therapies that are unavailable due to rigid trial designs, they lose faith in the system. Incentivizing compassionate use is not about undermining scientific integrity; it is about ensuring that the ethical obligations of drug development extend to those who fall outside traditional protocols.

Dravet syndrome is just one of many rare pediatric diseases facing similar challenges. The experiences of Odlaug’s family highlight a broader issue within the healthcare system that affects countless others. If the medical community truly prioritizes patient welfare, it must create a framework where hope is not limited by eligibility criteria and where companies that choose compassion are supported rather than penalized.

As the landscape of rare disease treatment evolves, Odlaug’s advocacy underscores the urgent need for systemic change. The goal is clear: to ensure that every child, regardless of their specific circumstances, has access to the therapies that could change their lives.