Elamipretide dosage and evidence

What is Elamipretide?

How does Elamipretide work?

It sticks to cardiolipin, a fat in the inner wall of mitochondria. That helps hold the folds of the wall in shape, so the cell's power plant makes energy (ATP) better.

What have studies in people found about Elamipretide?

Elamipretide has a large, well-reported record in people, and most of it is negative. It has a fast-track FDA approval for Barth syndrome, a very rare inherited disease. That approval rests on a 12-patient trial that missed both its main goals, plus a follow-on where everyone got the drug. A large final-stage trial in inherited muscle disease missed its goals. So did mid-stage trials in heart failure and in dry macular degeneration, an eye disease of aging.

• Inherited muscle disease: 218 adults with a confirmed mitochondrial muscle disease, a problem with the cell's energy factories, got 40 mg a day by shot or a dummy shot for 24 weeks. Their average age was 45.6 and 64% were women. At the start they could walk 336.7 metres in 6 minutes. The drug did not help on either main measure. Walking distance changed by 3.2 metres less than on the dummy, and fatigue scores did not differ. The authors call this top-grade evidence that it improves neither.
• Dry macular degeneration: 176 people aged 55 or older got 40 mg a day (117 people) or a dummy shot (59 people) for 48 weeks. Both main measures failed: vision in dim light and the size of the damaged patch. On extra scan measures that were not the main test, the eye's light-sensing layer wore away 43% and 47% less on the drug. More people gained at least 10 letters of dim-light vision, 14.6% against 2.1%. Side effects hit 86% on the drug and 71% on the dummy, mostly shot-site reactions.
• Heart failure: 71 people with a weak heart pump, pushing out 31% of its blood per beat on average, got a dummy shot, 4 mg or 40 mg a day for 28 days. Heart size on scans did not change on either dose, and neither did the pumping measure.
• The trial behind the approval: 12 people with Barth syndrome took 40 mg a day or a dummy shot for 12 weeks, rested 4 weeks, then swapped. It missed both main measures, a 6-minute walk and a symptom score. In the follow-on, 10 kept going and 8 reached 36 weeks. By then their 6-minute walk had improved by 95.9 metres, with no comparison group.
• The long follow-on of that same group (already cited on this page) reports 10 patients and a total gain of 96.1 metres over 168 weeks. Shot-site reactions were the most common side effect.

What this does not tell you: Nothing here describes elamipretide in a healthy person, at any age, for any length of time. Every trial was in people with a diagnosed disease, taking a daily shot of 4 to 40 mg for 4 to 76 weeks. The Barth syndrome approval rests on 12 patients whose trial missed its goals, plus a follow-on with no comparison group in 10. That is why it is a fast-track approval that still needs confirming. The eye result that held up is a scan measure, from a trial that missed what it set out to measure. And the biggest, best test of the main idea, that it boosts the cell's energy factories, came back flat.

The state of the research

The evidence, in charts

The studies we cite

• Study in people2023
  Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

  It was tested properly, at full scale, and it failed. 218 people with an inherited muscle disease caused by faulty mitochondria got elamipretide or a dummy injection, and nobody involved knew which. Both of the things the trial was built to settle came out flat. Walking distance in six minutes was 3.2 metres worse on the drug than on the dummy. The journal graded this as the strongest class of evidence that elamipretide does not improve walking or fatigue at six months.

  218 participants, phase 3, randomised and placebo controlled. Both primary endpoints missed. The six minute walk difference was minus 3.2 metres, favouring placebo, and the paper carries a Class I evidence classification that elamipretide does not improve walking distance or fatigue at 24 weeks.

  PMID 37268435 Neurology
• Study in people2024
  Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER

  A handful of patients kept improving for years, and there was nobody to compare them against. Ten people with Barth syndrome stayed on elamipretide in an extension where everybody got the drug. Their six minute walking distance rose by 96.1 metres over 168 weeks, a bit over three years. Reactions where they injected were the most common side effect. With no untreated group, growing older and getting practised at the walking test cannot be separated from the drug. Ten people is also too few to catch rare harms.

  Ten Barth syndrome patients in the open-label extension: 6-minute walk distance improved cumulatively by 96.1 m at week 168 with injection-site reactions the most common adverse event.

  PMID 38602181 Genetics in Medicine
• Study in people2025
  ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation

  This trial did not do what it set out to do. It gave 176 older people with dry macular degeneration a daily elamipretide shot or a dummy one for eleven months. The two things it was built to measure, reading in dim light and the size of the damaged patch at the back of the eye, came out the same in both groups. Scans of the light sensing layer looked better on the drug, but that was looked at afterwards. Side effects were commoner on the drug.

  176 patients randomized (117 elamipretide, 59 placebo) to 40 mg daily subcutaneously for 48 weeks: both primary endpoints missed. Secondary imaging measures showed 43% less complete ellipsoid zone loss and 47% less partial attenuation at nominal significance, and adverse events in 86% versus 71%.

  PMID 39605874 Ophthalmology Science
• Study in people2020
  Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial

  Elamipretide was tested in failing hearts and it changed nothing. Seventy one people with a weak heart pump got a dummy injection or one of two elamipretide doses, daily for four weeks. Ultrasound scans of how much blood the heart held and how much it pushed out looked the same in all three groups. The trial was small and short, so it could only have caught a fairly large effect. It did not find one.

  71 patients randomized to placebo, 4 mg or 40 mg daily for 28 days: no significant change in left ventricular end systolic volume or ejection fraction versus placebo (4 mg p = 0.90, 40 mg p = 0.28). Tolerability was similar across the three arms.

  PMID 32068002 Journal of Cardiac Failure
• Study in people2021
  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

  The trial behind elamipretide's approval missed both of its targets. Twelve people with Barth syndrome, a rare inherited heart and muscle disease, took the drug for twelve weeks and a dummy injection for twelve weeks, each person trying both in turn. Walking distance and symptoms did not separate. Everyone was then offered the drug openly, and the eight who stayed nine months walked considerably further. There was no comparison group in that second stretch, so improvement over time and the drug cannot be told apart.

  12 subjects crossed over between 40 mg per day and placebo for 12 weeks each: neither primary endpoint was met. In the uncontrolled open-label extension, 8 subjects reaching week 36 improved by 95.9 metres on the 6 minute walk (p = 0.024).

  PMID 33077895 Genetics in Medicine
• Review of studies2025
  Forzinity (elamipretide) injection, NDA 215244 accelerated approval letter

  The FDA's approval letter. Forzinity got early, conditional approval to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg. The company must run another study to confirm it works.

  FDA accelerated approval of Forzinity (elamipretide) to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg, under section 506(c) with post-marketing confirmation required.

  Source U.S. Food and Drug Administration
• Animal study2013
  The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin

  In rats. SS-31 stuck tightly to cardiolipin in mitochondria. After blood flow to the kidney was cut off, it protected the mitochondria and helped them make energy again faster.

  SS-31 binds cardiolipin on the inner mitochondrial membrane with high affinity, protecting cristae and accelerating ATP recovery after renal ischemia in rats.

  PMID 23813215 Journal of the American Society of Nephrology