Patient Group Pushes FDA to Take Action on Drug

Rare Daily Staff

The Barth Syndrome Foundation said it has delivered a petition with nearly 20,000 signatures to the U.S. Food and Drug Administration asking the agency to review for marketing approval Stealth Biotherapeutics experimental therapy elamipretide to treat the ultra-rare condition.

The foundation said that despite compelling evidence that elamipretide has been well-tolerated and has demonstrated clinical benefit in Barth syndrome, the FDA has refused to review an application to approve the drug to date.

In 2021, the U.S. Food and Drug Administration notified Stealth Biotherapeutics that it would not consider its application seeking approval for elamipretide as a treatment for the mitochondrial disease. The agency told the company it needed to produce evidence of the drug’s efficacy in a larger population of Barth syndrome patients than it studied, but the company believes it has exhausted the population in the United States of patients who fit the clinical trial criteria.

Patients have lobbied the agency to give the drug a hearing, but there is growing concern that if the FDA fails to act, elamipretide will become unavailable to patients, who say the drug has given them the ability to lead a normal life.

The case highlights the challenges ultra-rare disease drug developers face in advancing therapies for small populations and how different divisions within the agency may take different approaches to reviewing therapies for ultra-rare conditions.

Emily Milligan, executive director of the Barth Syndrome Foundation said that people with the condition have experienced greater than 40 percent improvement in heart function,

greater than 25 percent improvement in exercise tolerance, and greater than 40 percent improvement in muscle function, none of which is expected in the natural course of Barth syndrome. But the FDA believes the studies have been conducted in too few a number of patients for it to interpret the results.

“This has helped make transformational and meaningful changes in their lives. There simply aren’t enough people with Barth syndrome, though, to meet the impossible statistical requirements of the FDA to give elamipretide a full drug review,” said Milligan. “In our many meetings with Congress, we have been assured that the FDA has the regulatory flexibility to review these data, yet they have not used it. This is a systemic problem affecting all who seek treatments for ultra-rare diseases.”

Barth syndrome is a life-threatening, genetic disease primarily affecting males. Some 85 percent of deaths due to Barth syndrome occur by age 5. It is characterized by cardiac abnormalities often leading to heart failure and reduced life expectancy, recurrent infections, muscle weakness, and delayed growth. There are currently no FDA-approved treatments for Barth syndrome, and there are no other potential therapies in clinical development.

Elamipretide is an experimental mitochondrial protective agent that has been shown in preclinical studies to normalize mitochondrial structure and function and improve cell viability and organ function across a spectrum of disease models, including models of cardiovascular, renal, metabolic, skeletal muscle, neurodegenerative, and genetic mitochondrial disease. Elamipretide readily penetrates cell membranes and transiently localizes to the inner membrane of the mitochondria where it interacts with cardiolipin.

In an effort to move the FDA, Shelley Bowen, co-founder and director of family services for the Barth Syndrome Foundation, launched a Change.org petition calling on the agency to give a full and fair hearing to the drug. You can listen to the recent RARECast podcast with her below.

“For many Barth syndrome families, elamipretide represents their only hope for an affected child to have an increased chance to live into adulthood and to enjoy a life with reduced debilitating weakness and fatigue that precludes them from going to school, playing with friends, or holding a job,” said Kate McCurdy, co-founder and chair of the board of Barth Syndrome Foundation, who lost her son Will to the disease in 2014.

She said during the ten years since Stealth began development of elamipritide, two clinical trials and two dozen FDA meetings later, more than 10 percent of the global Barth syndrome patient population has died as the result of this disease. Meanwhile, elamipretide has been shown to be well-tolerated and has demonstrated clear, statistically significant improvements relative to the natural history of the disease.

“Patients who have no approved treatment options deserve access to this medicine. It is unconscionable that the FDA refuses to even fully review the data,” said McCurdy. “We implore them to be fair and equitable and to utilize the appropriate flexibility that has been granted to them by the U.S. Congress for cases just like ours.”

Photo: Kate McCurdy, board chair of Barth Syndrome Foundation, outside the FDA with the organization’s petition