Stealth's patience rewarded as FDA approves Barth drug

Stealth BioTherapeutics has claimed FDA approval for Forzinity, the first treatment for ultra-rare disease Barth syndrome, just a few months after it was turned down by the regulator.

Forzinity (elamipretide) can be used to treat patients weighing at least 30 kg with Barth syndrome, an X-linked, inherited mitochondrial disorder that causes an enlarged and weakened heart, skeletal muscle problems and infections. It is very rare, affecting only around 150 people in the US.

The drug has had a tricky path to market, as the FDA rejected Stealth's first marketing application in 2019 and rejected the second in May against the advice of its own advisory committee. While the Needham, Massachusetts-based company said at the time it had a path forward to approval, it was nevertheless forced to cut staff to eke out cash in the interim.

After the fresh delay, several lawmakers in the US wrote to FDA Commissioner Marty Makary, asking for an explanation for the decision amid an outcry from the Barth syndrome community and a swift decision on approval.

Barth syndrome mainly affects males and typically starts with severe heart failure in infancy that can lead to premature death. Those who survive into adolescence and adulthood often have fatigue, poor stamina, and exercise intolerance.

Forzinity is believed to work by binding to the inner part of the mitochondria, improving mitochondrial structure and function, according to the FDA, which has granted accelerated approval for the drug and will require a positive confirmatory, placebo-controlled trial to remain on the market long-term.

Stealth's latest application included data from a phase 2 clinical trial that showed a 45% improvement with the once-daily, injectable drug in the strength of the muscle used to straighten the leg at the knee that correlated with improvements on six-minute walking tests (6MWT) – a well-established clinical endpoint.

The FDA initially said that knee extensor muscle strength was not a valid endpoint, but subsequently agreed to consider it on the grounds that it is "likely to predict patient benefit, such as an ability to stand more easily or walk farther."

Stealth's chief executive, Reenie McCarthy, called the approval a "pivotal victory for the Barth syndrome community" and pledged to continue providing expanded access to children weighing less than 30 kg who are currently receiving treatment or require emergency access to the drug, while data on Forzinity's benefits in that younger population – typically aged below five – is generated.

Most infants with Barth syndrome die in the first 12 months of life.

"We are committed to the continued development of therapies to treat all patients with Barth syndrome and other devastating diseases of mitochondrial dysfunction," she said. Stealth has said it intends to launch Forzinity in the fourth quarter, but has not yet disclosed its pricing strategy for the drug.

Elamipretide is also in phase 3 trials involving patients with dry age-related macular degeneration (AMD) and primary mitochondrial myopathy.