SS-31 / elamipretide

12 participants

The randomized study found no significant advantage in walking distance or fatigue. FDA later granted accelerated approval using strength gains measured during an uncontrolled extension.^1295,1296

Who the approval covers

The US indication covers adults and children with Barth syndrome weighing at least 30 kg. A new controlled trial is recruiting to confirm clinical benefit.^1297,1298

Why the decision was contested

FDA’s clinical and statistical reviewers recommended against approval on the submitted evidence. The final decision accepted greater uncertainty because the disease is rare and serious. The strength result still needs confirmation.¹²⁹⁶

The larger myopathy trial

MMPOWER-3 randomized 218 people with primary mitochondrial myopathy. Walking distance and fatigue did not improve over placebo. A later genetic-subgroup finding led to NuPOWER, now completed without posted results.^{1299,1300,1301}

Other trials

Heart disease

PROGRESS-HF, the preserved-ejection-fraction trial and IDDEA-HF each missed its main outcome. Together they tested different heart-failure populations and treatment periods. The separate EMBRACE heart-attack study also missed its main infarct-size outcome.^{1302,1332,1333,1303}

Eye disease

Two small open-label groups reported visual improvements. ReCLAIM-2 then randomized 176 people and missed its main vision and geographic-atrophy outcomes. Exploratory retinal findings led to the ongoing phase 3 ReNEW trial.^{1304,1305,1306,1307}

Aging and energy

A single-infusion trial in 39 selected older adults found a mixed result for muscle ATP production capacity. The prespecified endurance test was negative, and the ATP difference was absent at day seven. SHAPE, a newer injection study, has no posted outcomes.^1308,1309

Laboratory and regional research

Chinese and Russian sources add animal experiments involving inflammation, brain injury and mitochondrial function. A 2025 mouse study found some functional improvements without reducing measured cardiac DNA-methylation age. These experiments help frame the questions for human trials.^{1310,1311,1312}

Safety and formulation

12 of 12

Every participant in the Barth crossover trial had a local reaction during elamipretide treatment, compared with eight during placebo. Redness, itching, pain and firmness were common.¹²⁹⁷

Allergy and kidney function

The label warns about serious allergic reactions, including reactions that begin after months of treatment. Kidney impairment raises drug exposure and changes the labeled adult dose in severe cases.¹²⁹⁷

Use the product-specific information

Forzinity is a ready-to-use solution. It contains benzyl alcohol and must not be used in newborns. The label gives specific handling, storage and discard instructions. Investigational formulations in older studies may differ.¹²⁹⁷

Read the complete safety record

The heart-attack trial registry records more deaths and serious adverse events in the active group, with causality and reporting details requiring careful interpretation. The small pediatric case literature includes both improvements and later deaths in complex circumstances.^1313,1314

Common questions

01 Who is Forzinity approved for?

In the United States, Forzinity is approved to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg. FDA granted accelerated approval on September 19, 2025. The approval remains dependent on confirmation of clinical benefit.^1315,1297

02 Are SS-31, elamipretide and Forzinity the same thing?

SS-31, MTP-131 and elamipretide are names used for the same peptide. Forzinity is the approved prescription product containing elamipretide. Its label describes a specific ready-to-use injection, including its concentration and preservative.¹³¹⁶

03 Why was it approved after a negative randomized trial?

FDA relied on improved knee-extensor strength during the longer, uncontrolled extension. The final decision accepted greater uncertainty because Barth syndrome is very rare, serious and had no approved treatment. FDA required another controlled trial to confirm benefit.^1296,1315

04 Did FDA reviewers agree about the evidence?

No. Clinical, statistical and cross-disciplinary reviewers recommended against approval on the submitted evidence. They raised concerns about an uncontrolled, effort-dependent strength test and the loss of participants over time. The final signatory accepted that uncertainty under accelerated approval.¹²⁹⁶

05 What will the confirmatory Barth trial test?

4TAZPower is recruiting and plans to enroll 48 participants. It will compare elamipretide with placebo over 72 weeks using a combined measure of walking, getting up and moving, and repeated sit-to-stand performance. FDA requires the final report by March 2030.^1298,1315

06 What happened in the randomized Barth syndrome trial?

Twelve men and boys took elamipretide and placebo in separate 12-week periods. Walking distance, fatigue and knee strength did not improve significantly over placebo. Longer follow-up reported improvements after everyone received the drug.¹²⁹⁵

07 How strong is the longer-term Barth evidence?

Eight participants continued through 36 weeks of the extension. Their walking distance and strength improved from baseline. A later comparison with untreated patients also favored treatment, but it reused the same small trial group and was not randomized.^1295,1317

08 Did it work in primary mitochondrial myopathy?

The largest published trial randomized 218 people to elamipretide or placebo for 24 weeks. It found no improvement over placebo in its two main outcomes: six-minute walking distance and reported fatigue. Exploratory results in a genetic subgroup led to further research.¹²⁹⁹

09 Why do some mitochondrial-myopathy studies sound more positive?

Earlier studies were smaller and shorter. A 30-person crossover trial found less reported fatigue but missed its main walking endpoint. The later 218-person trial missed both walking and fatigue endpoints. The early fatigue result remains exploratory.^1318,1299

10 Are the early MMPOWER trials independent confirmation?

MMPOWER-2 enrolled 30 people from the original 36-person MMPOWER study. It tested a different route and treatment period, but largely followed the same people.^1319,1318

11 Why are researchers looking at particular mitochondrial gene variants?

An exploratory reanalysis of MMPOWER-3 found a walking signal in a small subgroup with particular gene defects and progressive eye-muscle weakness. NuPOWER tested the genetic subgroup prospectively and is now completed; its results have not been posted.^{1300,1299,1301}

12 What happened after the mitochondrial-myopathy subgroup finding?

The prospective NuPOWER study is listed as completed with 102 participants. No results are posted in the current registry record, so its outcome cannot yet settle the earlier subgroup finding.^1301,1300

13 Does SS-31 treat heart failure?

The controlled trials have not shown a clear benefit. PROGRESS-HF, with 71 participants, missed its main ventricular outcome. A separate 47-person preserved-ejection-fraction trial missed its main filling-pressure measure. The 306-person IDDEA-HF conference report found no advantage in its main blood-marker outcome or congestion measures.^{1302,1332,1333}

14 Did SS-31 limit damage after a heart attack?

EMBRACE STEMI tested an infusion during emergency coronary treatment. It did not significantly reduce its main measure of infarct size, and other prespecified cardiac outcomes did not improve.¹³⁰³

15 Were there serious events in the heart-attack trial?

The trial registry records deaths in 10 of 150 elamipretide recipients and 3 of 147 placebo recipients, with serious adverse events in 20 and 14, respectively. These are descriptive totals in people having a heart attack. They need careful review alongside the full clinical report before assigning a cause.¹³¹³

16 What did the macular-degeneration trial find?

In 176 participants, elamipretide missed both main outcomes: low-light visual acuity and growth of geographic atrophy. Exploratory measurements of the retinal ellipsoid zone favored treatment. A phase 3 eye-disease trial is now underway.^1306,1307

17 Why did the first eye studies look encouraging?

The first study had two groups totaling 40 people, all receiving elamipretide. Some vision measures improved among those who completed 24 weeks. There was no placebo comparison, and the later randomized ReCLAIM-2 trial missed its main outcomes.^{1304,1305,1306}

18 What about SS-31 eye drops?

A 12-person study tested elamipretide eye drops in an inherited optic-nerve disorder. Its main visual-acuity outcome did not improve over vehicle drops. Later visual-field analyses and open-label results encouraged further study.¹³²⁰

19 Is the eye-disease program continuing?

Yes. ReNEW is a phase 3 dry age-related macular degeneration trial listed as active but no longer recruiting. Its current registry reports 313 participants and no posted results. The earlier ReCLAIM-2 study missed its main vision and geographic-atrophy outcomes.^1307,1306

20 Has it been tested around kidney procedures?

A 14-person pilot study gave elamipretide or placebo during renal-artery stenting. It reported improvements in kidney blood-flow and filtration measures. The small, procedure-specific study leaves the size and reliability of any benefit uncertain.¹³²¹

21 Does a positive case report count as proof?

Case reports describe what happened to one person. The published MPAN report followed a woman who began treatment at 21; walking distance increased by about ten metres after three months. A controlled study would be needed to estimate how much change came from the drug.¹³²²

22 What happened in the early pediatric case series?

Three children with different mitochondrial disorders received investigational treatment alongside other care. The authors described improvements, but two infants later died in complex medical circumstances. The small, uncontrolled series cannot determine how much benefit or risk came from elamipretide.¹³¹⁴

23 Has SS-31 been tested in otherwise healthy older people?

Yes. One trial randomized 39 adults aged 60-85 who had low mitochondrial-function measurements. It tested a single intravenous infusion. The absolute change in ATP production capacity narrowly missed statistical significance; the percentage change favored elamipretide. The prespecified hand-muscle endurance test did not improve.¹³⁰⁸

24 Did the energy-production effect last?

The study found no difference from placebo in mitochondrial energy capacity seven days after the infusion. It did not establish a lasting improvement in physical function.¹³⁰⁸

25 Is there a newer study in older adults?

SHAPE is registered as a small, open-label study of daily injections in adults aged 65-80, with safety and tolerability as its main purpose. It has no posted results. Its recruitment field was last verified in December 2025, so current enrollment status needs confirmation.¹³⁰⁹

26 Does it reverse biological age?

A 2025 mouse study found improvements in some muscle and heart measurements after eight weeks. Heart DNA-methylation clocks did not become younger, and most transcriptomic-age measurements were unchanged. The study did not measure lifespan.¹³¹²

27 What does cardiolipin have to do with it?

Cardiolipin is a lipid in the inner mitochondrial membrane. Laboratory experiments link elamipretide to cardiolipin and nearby proteins involved in energy production. Researchers are still mapping those interactions to specific clinical effects.^1323,1324

28 Do positive reviews of mitochondrial treatments prove that SS-31 works?

Read which drugs contributed to the result. Reviews often combine elamipretide with CoQ10, MitoQ or other compounds. A pooled benefit across those treatments cannot tell you the effect of elamipretide alone.^1325,1326

29 Did Chinese or Russian research add anything?

The retrieved Chinese studies include mouse inflammatory injury and rat brain-injury experiments. A Russian conference report studied inflammatory signaling in an Alzheimer-like rat model. These sources broaden the preclinical picture; no new regional human efficacy trial was verified in those searches.^{1310,1327,1311}

30 Who funded the research?

Stealth BioTherapeutics funded many of the main trials and supplied drug or publication support for several case reports. Some investigators disclosed consulting roles or patents. Read those interests alongside the study design and results; the larger randomized trials remain central to judging benefit.^{1295,1299,1304,1314}

31 What side effects appeared in the trials?

Injection-site redness, itching and pain were common. In the short Barth trial, all 12 participants had an adverse event during elamipretide treatment, compared with ten during placebo. Two of ten extension participants stopped because of injection reactions.¹²⁹⁵

32 How common are injection-site reactions?

In the 12-person Barth crossover trial, every participant had a local reaction during elamipretide treatment, compared with eight during placebo. Redness, pain, itching and firmness were common. The same people took both treatments at different times. A separate ten-person study explored ways to reduce local reactions. Its small, unblinded design makes those results preliminary; cooling also reduced drug exposure.^1297,1334

33 How is an allergic reaction different from ordinary injection irritation?

The label describes allergic reactions involving the skin and respiratory symptoms such as cough. They can begin within minutes or months after treatment starts. Stop the medicine and seek immediate medical attention for an immediate allergic reaction; a serious reaction rules out restarting it.¹²⁹⁷

34 What happened to eosinophil counts?

Blood eosinophils sometimes rose after treatment began. Average counts peaked around three months and moved back toward baseline over six to twelve months or after treatment stopped. The small clinical program reported no accompanying clinical symptoms from those increases.¹²⁹⁷

35 What does the prescription label say about dosing?

For the approved Barth population weighing at least 30 kg, the label specifies 40 mg by subcutaneous injection once daily. Adults with severe kidney impairment who are not receiving dialysis use a reduced labeled dose. There is no approved dosing schedule for longevity.¹²⁹⁷

36 Why does kidney function matter?

Elamipretide and its metabolites leave the body mainly through urine. Drug exposure rose as kidney function declined, reaching about 125% above normal in severe impairment. The label reduces the adult dose in that group and has insufficient dosing information for dialysis or children with renal impairment.¹²⁹⁷

37 What is known about pregnancy and breastfeeding?

There are no human data adequate to assess pregnancy risk or passage into breast milk. Animal reproductive studies provide some background, but the prescribing decision requires an individual discussion with the treating clinician.¹²⁹⁷

38 Can newborns receive the marketed formulation?

The Forzinity label says not to use it in newborns because it contains benzyl alcohol. The approved population also has a minimum weight of 30 kg. Published compassionate-use infant cases involved investigational care and do not supply a neonatal prescription for the marketed product.^{1297,1328,1329}

39 Does Forzinity need to be reconstituted?

No. It comes as a ready-to-use solution. The label says not to mix it with other products in the same syringe.¹²⁹⁷

40 How is the approved product stored?

Keep unopened Forzinity refrigerated at 2-8°C and do not freeze it. After first use, the vial can remain refrigerated or be kept at 20-25°C. Discard it eight days after first use, even if liquid remains.¹²⁹⁷

41 Has anyone tested SS-31 with MOTS-c or NMN?

Our focused literature search found no controlled study establishing an order for SS-31 and MOTS-c. Two mouse studies tested SS-31 with NMN and reported effects from the combination. Controlled human evidence for those combinations was not identified. The label describes separate interaction studies with aspirin, clopidogrel and heparin.^{1335,1336,1297}

42 Does the time of peak blood concentration tell me how long it works?

After the approved subcutaneous injection, blood concentrations peak in roughly half an hour to an hour. A clinical effect has to be measured separately. The older-adult study found no ATP-capacity difference from placebo seven days after a single infusion.^1297,1308

43 Can athletes assume it is permitted because the name is absent from a list?

The 2026 and 2027 WADA documents use open-ended drug classes as well as named examples. We did not resolve elamipretide’s classification across those classes. A tested athlete needs a current determination from the relevant anti-doping authority.^1330,1331