FDA AdCom votes in favour of Stealth’s Barth syndrome drug
AUS Food and Drug Administration (FDA) advisory committee (AdCom) has voted in support of Stealth BioTherapeutics’ first-line Barth syndrome drug, despite a trial studying the drug not meeting its primary endpoint.
The Cardiovascular and Renal Drugs Advisory Committee voted 10-6 supporting Stealth’s elamipretide for the treatment of Barth syndrome, an ultra-rare genetic disorder caused by mutations in the TAZ gene, which primarily affects males.
The life-threatening disease – which causes symptoms like cardiomyopathy and growth delays – has no cure, and no other therapies in late-stage clinical development, according to the Barth syndrome Foundation. The FDA is expected to decide whether to approve the new drug application in January 2025.
During the committee meeting, the panel discussed findings from the SPIBA-201 clinical trial (NCT03098797). The trial, which assessed the impact of elamipretide in 12 male patients over 12 weeks of daily treatment, failed to meet the primary endpoint of improving walking distance.
However, the AdCom heard from patients, doctors, and parents of children with Barth syndrome, saying that the drug had helped patients gain weight, strength, and stamina, advocating for elamipretide’s approval. Jacob Wilson, a 24-year-old male with Barth syndrome told the panel the medicine “made him feel like a new person”.
Elamipretide has previously faced rejection from the FDA. In August 2021, Stealth filed a new drug application (NDA) for the candidate, however the FDA responded in October of the same year with a refuse-to-file letter, stating that the NDA “did not contain an adequate and well-controlled trial that provides evidence of effectiveness”. Stealth did not conduct another Phase III study, despite advice from the FDA to do so. Its initial application was linked to the SPIBA-001 study (NCT04689360), a Phase III trial that included both treated patients from SPIBA-201 and new, untreated patients.
Despite the trial meeting its primary endpoint, the FDA raised concerns about how the data were analysed. Results were compared to an open-label extension from the Phase II/III SPIBA-201 crossover study and historical control data from 19 subjects monitored between 2012 and 2019 at the Johns Hopkins Kennedy-Krieger Institute. This approach was criticised by the FDA.
Elamipretide (also known as SS-31, MTP-131 and Bendavia) is a small mitochondrially-targeted tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH2) that appears to reduce the production of toxic reactive oxygen species and stabilize cardiolipin.
