TAZPOWER Trial: What the Results Actually Show

The TAZPOWER trial did not show better walking distance or less fatigue with elamipretide, also called SS-31, than with placebo, an inactive comparison treatment. Later follow-up reported gains, but everyone knew they were receiving the drug and there was no simultaneous placebo group.

Both findings matter. The first is the controlled result. The second helped support a narrow Barth syndrome decision and a requirement for another trial. Neither establishes a benefit for everyday tiredness or healthy aging.

What question did the TAZPOWER trial ask?

Could elamipretide help people with Barth syndrome walk farther and feel less tired?

Barth syndrome is an inherited disorder caused by changes in the TAZ gene that disrupt cardiolipin, a fat needed for mitochondrial structure. Mitochondria are the parts of cells that make usable energy. The condition can affect the heart and skeletal muscles.

SS-31 is a peptide, a short chain of protein building blocks, studied for binding that fat. A biological target gives researchers a reason to test treatment. It doesn't establish that treatment helps. The wider SS-31 benefits evidence covers questions beyond Barth syndrome.

Who took part, and how did the comparison work?

TAZPOWER enrolled 12 males, ages 12–35, with genetically confirmed Barth syndrome at Johns Hopkins. All could complete the walking test. Entry required stable medicines and specified weight and kidney-function thresholds. Recent hospitalization, uncontrolled high blood pressure and previous heart transplantation were among the exclusions.

Treatment order was randomized, meaning assigned by chance. The study was double-blind: participants and the study team didn't know which treatment came first. Each person received 12 weeks of elamipretide and 12 weeks of placebo, with four weeks between them.

That is a crossover design: each person receives both treatments and serves as their own comparison. The four-week washout, a break between treatments, made the controlled study 28 weeks long.

The study used 40 mg daily injected under the skin. That is a trial fact, not an individual prescription. The TAZPOWER registry record, NCT03098797, documents the plan and posted results. Stealth BioTherapeutics funded the study.

What was measured, and what happened?

The two primary endpoints, the main outcomes chosen before results were known, were six-minute walking distance and the Barth Syndrome Symptom Assessment Total Fatigue Score. The latter measures disease-specific tiredness; lower scores mean fewer symptoms.

Neither main outcome improved compared with placebo. The 2021 Genetics in Medicine paper by Thompson and colleagues reported:

P values measure how surprising a result would be if there were no treatment difference. These results did not establish an advantage for elamipretide. All 12 participants completed both treatment periods.

What the paper's side-effect table showed

An adverse event is any medical problem recorded during treatment, whether or not the medicine caused it. Local reactions were common. Selected rows from Table 2 of the original paper follow; the same 12 people appear under each treatment.

Most events were mild or moderate. Two of the 10 people who entered the extension stopped because of injection-site reactions. A small study cannot reliably reveal uncommon harms. Forzinity's prescribing information also warns that allergic reactions, including serious reactions requiring emergency treatment, have been reported, and that they may occur within minutes to months after treatment starts.

What the 168-week extension added

The extension was open-label, meaning everyone knew they were receiving elamipretide. Ten people entered; eight reached week 168, a little over three years.

The 2024 Genetics in Medicine follow-up reported a 96.1-meter average gain in six-minute walking distance from the extension baseline at week 168. Fatigue scores stayed below baseline, and heart-imaging measurements showed favorable trends. The extension's main goals were safety and tolerability; walking and fatigue were secondary outcomes, additional measures beyond those goals.

That gain is worth studying. It is also a comparison with a starting measurement, rather than with people receiving placebo at the same time. Expectations, repeated-test practice and changes in care can influence what happens over years. The extension therefore cannot establish the treatment's effect as securely as a successful randomized comparison.

Could natural-history records strengthen the evidence?

A 2022 Orphanet Journal of Rare Diseases study by Hornby and colleagues compared eight extension participants with 19 untreated people. This was an external control: comparison patients drawn from records outside the treatment trial.

The adjusted walking difference favored elamipretide by 79.7 meters at week 64 and 91.0 meters at week 76. Researchers used statistical matching to make the groups more comparable. They acknowledged that matching could not account for every difference in medicines or medical care. This added context, but did not recreate random assignment.

Why FDA required another Barth syndrome trial

As of October 1, 2026, the day this article was written, Forzinity has a narrow Barth syndrome indication following FDA's September 19, 2025 decision. The approval letter covers improving muscle strength in adults and children weighing at least 30 kilograms. It requires a controlled follow-up trial. The Forzinity approval anniversary explains the decision's history.

FDA used knee-extensor strength, the force of the muscles that straighten the leg, as a measure reasonably likely to predict patient benefit. That is accelerated approval: earlier access while another trial checks whether the predicted benefit holds. The FDA trial snapshot says knee-extensor strength did not increase during the 12-week randomized comparison; the increases FDA relied on were observed during the open-label extension. Walking distance and fatigue, the trial's main outcomes, were not the basis for approval.

As of October 1, 2026, the day this article was written, that follow-up study is underway. On July 8, 2026, Mighty Therapeutics, the parent company of Stealth BioTherapeutics, announced that the first participant had been dosed. The 4TAZPower registry, updated September 17, 2026, lists recruitment open, 48 participants planned and 72 weeks of treatment. Its main measure combines walking, getting up and moving, and repeated chair rises. These are study plans, not new results.

The separate Forzinity prescribing-information guide explains the branded label. The MMPOWER-3 results concern another muscle disease and another trial; neither study can substitute for the other.

What this means for a compounded prescription

SS-31 is coming soon to Promise — add me to the list. Through Promise, SS-31 will be dispensed as a compounded medication, which is different from an FDA-approved product: the formulation Promise will offer is not FDA-approved. A compounded medicine is prepared by a pharmacy for an individual prescription. TAZPOWER did not test the preparation Promise will offer or general wellness use.

MOTS-c also appears in mitochondrial discussions, but it is a different peptide studied as a signal through AMPK, the cell's fuel sensor. Its original Cell Metabolism study tested treatment in cells and mice. Those findings cannot extend TAZPOWER's results to another compound or establish that combining them helps.

What belongs in the visit

The useful discussion starts with the person's condition, how closely the evidence matches it, what outcome would be followed and how unwanted effects would be recorded.

A licensed provider may still prescribe — that decision is between you and your doctor. At Promise, a licensed provider reviews every SS-31 request and may prescribe or decline on medical eligibility; not everyone qualifies. The prescriber sets the actual dose and follow-up plan.