A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism

Reid Thompson W, Hornby B, Manuel R, et al. · Genetics in Medicine

Neither primary endpoint separated from placebo in the blinded crossover: 6-minute walk -0.8 m (p=0.97) and the Barth Symptom Assessment fatigue score +0.06 (p=0.89), with no separation on muscle strength by dynamometry (+6.7 newtons, p=0.65) or on any other secondary endpoint. The gains come from the uncontrolled open-label extension, where walk distance rose 95.9 m against each participant's own baseline by week 36 (p=0.02) among the eight who reached it. No mechanism marker moved in either part — FGF21, GDF15, the blood-spot monolysocardiolipin-to-cardiolipin ratio and 3-methylglutaconic acid were unchanged throughout. Injection-site erythema occurred in 12/12 on drug against 3/12 on placebo, and two of the ten who entered the extension stopped for injection-site reactions.

Population

12 males with genetically confirmed Barth syndrome, aged 12-35 (TAZPOWER)

Intervention

Elamipretide 40 mg subcutaneous daily for 12 weeks, crossover

Comparator

Placebo, 4-week washout between periods

Limitations

Twelve participants, with a lower age limit of 12 years in a disorder that usually presents in infancy. The paper's own limitations say the open-label gains lack a control group and cannot exclude a placebo effect, and that the 6-minute walk is subject to learning effects; the week-36 comparison is a paired test against baseline in eight people. Funded by Stealth BioTherapeutics, with one author employed by the sponsor. No joint or cartilage endpoint of any kind.