The grandfather of a child with a rare disease is calling for greater inclusion in clinical trials, highlighting the barriers faced by families seeking access to investigational therapies. Theron (Ted) Odlaug advocates for children like his granddaughter, Anna, who suffers from Dravet syndrome, a severe form of childhood epilepsy linked to mutations in the SCN1A gene. Despite being on multiple medications approved by the Food and Drug Administration (FDA), Anna experiences frequent seizures, underscoring the urgent need for more inclusive research protocols.
Odlaug describes the difficult choices families face as they navigate between standard care and experimental treatments. His granddaughter has endured hundreds of seizures despite receiving approved therapies, which are often prescribed off-label for Dravet syndrome. This situation has pushed Odlaug into a role beyond that of a grandfather; he has become a passionate advocate for access to clinical trials and investigational treatments.
After over 40 years in health care leadership, Odlaug emphasizes that while many promising therapies exist, eligibility criteria often exclude the very patients who need them the most. “Even when the FDA is willing to authorize expanded access,” he states, “families like ours find themselves without options because of rigid trial protocols.”
Dravet syndrome exemplifies the challenges faced by families. Although recent advancements have led to several FDA-approved therapies, many children continue to suffer from debilitating symptoms. Investigational therapies hold significant promise, yet access remains limited due to specific exclusion criteria such as age or current medications.
The system currently in place for expanded access, commonly referred to as compassionate use, is often misunderstood. The FDA typically approves over 99% of requests for expanded access within days, indicating that the agency is not the primary obstacle. Instead, the decision-making power rests with the pharmaceutical companies, which often decline compassionate use requests to protect ongoing clinical trials and manage regulatory concerns.
Odlaug points out that this creates a paradox where patients with the greatest need—those who are ineligible for trials—are the least likely to access new therapies. His granddaughter faced a recent setback when attempts to adjust her medication to qualify for the Stoke Therapeutics EMPEROR gene therapy trial failed due to increased seizures. The company has not approved compassionate use for her, leaving her without potential treatment options.
Investigational approaches like antisense oligonucleotides and gene therapies are making strides through clinical trials, yet many patients are excluded based on criteria that do not take into account their dire circumstances. Families often receive implicit and explicit messages to wait for another trial or approval, a frustrating prospect for children with severe neurodevelopmental disorders where time is of the essence. For these children, ongoing seizures and developmental regression can cause irreversible damage.
While mandating compassionate use is unlikely to succeed and might hinder innovation, Odlaug suggests that well-designed incentives could encourage companies to act more compassionately without compromising their business interests. He proposes that Congress and the FDA consider creating incentives that would foster a culture where compassion and innovation coexist.
Building public trust in rare-disease drug development is crucial, as it relies on the collaboration of caregivers, clinicians, and advocates. When families observe that investigational therapies are available but inaccessible due to strict protocols, their trust diminishes. Odlaug asserts that encouraging compassionate use aligns ethical leadership in drug development with the responsibility to support those left behind by clinical trial designs.
Dravet syndrome is just one of many rare pediatric diseases facing similar challenges. Odlaug concludes that if the healthcare community truly prioritizes patient welfare, the system must evolve to ensure that hope is not confined to rigid inclusion criteria. The focus should be on fostering an environment where companies are supported for choosing compassion, ultimately benefiting the children who need it most.
