Eddie Darton, M.D., is executive medical director of Safety Evaluation & Risk Management at Sarepta. He works on clinical trials evaluating an investigational gene therapy for individuals living with Duchenne. We’re sharing his journey to Sarepta and commitment to always keep trial participants safe as part of a series exploring the people and stories behind Sarepta’s genetic medicine revolution.
Hospital emergency departments tend to be fast-paced, sometimes chaotic environments. Providers need to process information quickly, think clearly and act decisively—all while keeping a watchful eye out for subtle or unexpected changes. “In the ER, you need to make split-second decisions. You can’t sit there and ponder all day,” Eddie said.
While Darton works in drug safety now, he began his career as a physician and worked for a time in the emergency department of a Naval hospital. Working in drug safety at a biotech company, where days are mostly spent at a computer pouring over patient data and charts, may seem a far cry from the ER. But the roles have more in common than you would think, according to Darton. That’s because both are about managing risk, mapping a path to the best outcome and always doing what is right for patients.
Bringing an open mind, with a high level of suspicion
After he transitioned from clinical care to working in drug safety, or pharmacovigilance, one of Darton’s biggest challenges was explaining his new role to people. “Everyone knows R&D, but they don’t know us,” he said.
Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other medicine/vaccine-related problem.1 More simply: “Our job is to monitor the safety of approved medicines and therapies in development,” Darton explained. “We’re there if you experience an issue with a therapy. And we do everything we can to make sure the participants in a clinical trial are as safe as possible.”
Drug safety professionals like Darton develop the safety protocol for all stages of a clinical trial, identifying the medical and laboratory tests that will monitor patient safety, agreeing with regulatory agencies on how trial data will be collected and clarifying how serious side effects will be expeditiously reported.
To develop a protocol, Darton studies all available data and literature to understand and anticipate safety risks. In rare diseases like Duchenne muscular dystrophy, where there is a smaller library of patient data (because the number of people affected is smaller and there are fewer participants in clinical trials), Darton must widen his search for safety information. “We look at what’s known from non-clinical studies and animal studies, and we extrapolate things we see in those studies to what we might see in humans,” he explained. “We also look at study data from other therapies in development. And we factor in the day-to-day real-world information we get from ongoing clinical studies. Only then do we have a good picture of safety concerns.”
In this way, Darton’s job is part scientist, part detective, part explorer of the unknown. “Working in gene therapy, we’re at the leading edge of science and so much of the field is new,” Darton explained. “You have to approach everything with an open mind but high level of suspicion, and then consider every angle.”
We want to make sure we’re keeping patients safe without making the drug trial process more burdensome.
A privilege to take this journey with patients
At Sarepta, Darton works on clinical trials evaluating an investigational gene therapy for boys with Duchenne. Although most of the trials to date have focused on younger boys, Sarepta also is exploring the safety and effectiveness of the therapy in patients who are older or non-ambulatory (meaning they can no longer walk unassisted). Because there is less clinical trial data for this population, there is less information to draw from when building a safety profile for the trial.
“This is a population that is under-investigated and so we have questions about participation and patient safety,” he said. “We are taking every step – from building the safety profile, to establishing monitoring measures, educating the trial investigators and working with regulators around the world – to ensure patient safety, which is always our highest priority.”
For example, Darton explained, because non-ambulant boys tend to be older and weigh more than younger clinical trial patient populations, the drug safety team evaluated whether there would be risks related to weight and higher dosing. Also, because Duchenne is a progressive disease that alters the body’s physiology, there are some measures that may register as atypical (compared with younger Duchenne patients) even before a gene therapy is administered, such as breathing difficulties. It’s up to Darton and the drug safety team to evaluate what would fall within expected range for a Duchenne patient at that age and stage of disease and what would raise a safety concern for this patient population.
“One of the main things we do is try to establish an expected baseline for trial participants so we can more accurately observe if there are concerning changes after a person is exposed to the therapy,” he said. “We want to make sure we’re keeping patients safe without making the drug trial process more burdensome with additional trips to the hospital or laboratory for tests and procedures.”
Patients’ and families’ needs are always at the front of Darton’s mind, and he considers it a privilege to partner with the Duchenne community on clinical studies. “I thank the families for allowing us to work with them on this journey. It’s a tremendous responsibility, but also an honor,” he said. “I want families to know that we’re with them every step of the way. They are never alone.”
1. World Health Organization. Pharmacovigilance. (https://www.who.int/teams/regulation-prequalification/regulation-and-safety/pharmacovigilance)
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Advocates & Innovators