Claim being evaluated

Is safe for human administration

A claim to investigate, not an established benefit. Each outcome below is assessed separately.

What the evidence suggests

Adverse events, including injection-site reactions, and discontinuations: Two independent automated assessments of this question disagreed, so the more cautious result is shown: very low certainty.

What remains unknown: Adverse event and discontinuation counts by arm for most trials, and the frequency and severity of injection-site reactions compared with placebo, are not reported. Safety beyond about one year, rare or serious harms, effects in children (only case reports and a small extension study) and effects in pregnancy and older adults with multiple conditions remain unknown. Interactions with other drugs and the unpublished registry results are also unknown.

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated by rule (no eligible human study was found), not reviewed by a person.

Certainty by outcome

Adverse events, including injection-site reactions, and discontinuations

Insufficient information to assess

Safety outcome · 15 studies · 655 participants

Not enough evidence to tell

Two independent automated assessments of this question disagreed, so the more cautious result is shown: very low certainty.

What the research measured: Outcome: adverse events, injection-site reactions and discontinuations versus placebo. In ReCLAIM-2 (176 randomized, 48 weeks), adverse events occurred in 86% of elamipretide patients versus 71% on placebo, and injection-site reactions (pruritus, pain, bruising, erythema) were more frequent with elamipretide. In the crossover trial in mitochondrial myopathy (30 participants), injection-site reactions were the most common events, mostly mild, with no serious adverse events or deaths. MMPOWER-3 (218 participants) described elamipretide as well tolerated with mostly mild to moderate events. PROGRESS-HF (71 participants) reported drug-related adverse event rates similar to placebo. The single-infusion heart failure trial (36 participants) reported no serious adverse events and stable vital signs. The dose-escalation and STEMI trials reported no increased safety concerns but gave no counts. In uncontrolled studies, all participants in two open-label AMD trials (21 and 19) had at least one mild or moderate event, and one participant in each withdrew because of an injection-site reaction. One child had a transient non-serious episode of abdominal pain with pancreatic enzyme elevation. Long-term open-label use in Barth syndrome (10 patients, 168 weeks) reported injection-site reactions as the most common event. No by-arm discontinuation data are reported from the randomized trials.

Reviewers’ note: At least one included study has no risk-of-bias assessment, so no certainty rating is given.

How the certainty was judged

GRADE domain judgments
Domain	Judgment	Why
Starting level	—
Risk of bias	—	All records are abstract-only or registry-only, so allocation, blinding and attrition cannot be checked. Safety in most placebo-controlled trials is reported only narratively ('well tolerated'), with no counts by arm. RoB2 judgments for the safety outcome are some concerns or high (MMPOWER-3, EMBRACE STEMI). Frequent injection-site reactions may have unmasked allocation.
Inconsistency	—	Studies report adverse events in different ways (narrative, percentages, or not at all). ReCLAIM-2 shows more adverse events with elamipretide (86% vs 71%), and injection-site reactions are described as common or frequent in several trials, while others state similar rates to placebo or no serious events. Pooling is not possible.
Indirectness	—	Studies span heterogeneous conditions, routes (subcutaneous, intravenous, topical eye), and durations from a single infusion to 168 weeks. Many are uncontrolled and lack a placebo comparator. Most report only narrative tolerability, with few specific data on injection-site reactions or discontinuations.
Imprecision	—	Adverse event counts, confidence intervals and discontinuation numbers are mostly missing. Many studies are small, and the abstract-only records give no event data by arm. Rare or long-term harms cannot be excluded.
Publication bias	—	Several abstract-only reports with narrative 'well tolerated' statements, case reports selected for publication, and a registered trial (Fuchs' dystrophy) that flags results but provides none. Sponsor and funding information is often missing.

Included studies

Elamipretide in pediatric Barth syndrome: from heart failure to school return. (Case report, 1 participants)
Expanded-Access Use of Elamipretide Improves Quality of Life in Patients With Rare Mitochondrial Disorders Characterized by Ophthalmic Symptoms: A Case Series. (Case series, 2 participants)
Cardiac pathology in a patient with a novel pathogenic variant c.703del (p.Ile235SerfsTer4) of the TAFAZZIN gene. (Case report, 1 participants)
ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration, Geographic Atrophy Growth, Visual Function, and Ellipsoid Zone Preservation. (Randomized controlled trial, 176 participants)
Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial. (Randomized controlled trial, 12 participants)
Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. (Single-arm trial)
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. (Randomized controlled trial, 218 participants)
Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. (Randomized controlled trial, 36 participants)
Phase 1 Clinical Trial of Elamipretide in Intermediate Age-Related Macular Degeneration and High-Risk Drusen: ReCLAIM High-Risk Drusen Study. (Single-arm trial, 21 participants)
Phase 1 Clinical Trial of Elamipretide in Dry Age-Related Macular Degeneration and Noncentral Geographic Atrophy: ReCLAIM NCGA Study. (Single-arm trial, 19 participants)
Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. (Randomized controlled trial, 71 participants)
A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. (Randomized controlled trial, 30 participants)
EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. (Randomized controlled trial)
Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. (Randomized controlled trial, 36 participants)
A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED) (Other design, 22 participants)

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · GRADE (handbook, 2013) · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

The questions and the studies screened

Population, intervention, comparator and outcome (PICO), and why each study was or wasn’t eligible.

Population: Any human population studied · Intervention: Elamipretide (SS-31) · Comparator: Placebo · Outcome: Adverse events, including injection-site reactions, and discontinuations

PLS-00036: not eligible (not primary study)
PLS-00097: eligible · indirect evidence (differs on comparator): Reports adverse events (non-serious abdominal pain with pancreatic enzyme elevation) and no discontinuation in a human patient; no placebo comparator.
PLS-00098: eligible · indirect evidence (differs on comparator, outcome): Reports tolerability of elamipretide in humans, but only narratively, without a placebo comparator or specific adverse events and discontinuations.
PLS-00099: not eligible (insufficient data)
PLS-00100: not eligible (insufficient data)
PLS-00101: eligible · indirect evidence (differs on comparator): A human infant received intravenous then subcutaneous elamipretide and tolerability is reported as well tolerated without significant side effects. There is no placebo comparator and the case is a single uncontrolled patient.
PLS-00102: not eligible (insufficient data)
PLS-00103: not eligible (insufficient data)
PLS-00104: eligible · direct evidence: Placebo-controlled trial in humans reporting adverse event incidence, including injection site reactions, as the primary safety end point.
PLS-00105: eligible · indirect evidence (differs on intervention, comparator, outcome, population): Humans given elamipretide with AE assessment as primary outcome, but via topical ophthalmic route. The vehicle control was the fellow eye in the same patients, and no injection-site or discontinuation data are reported.
PLS-00106: eligible · indirect evidence (differs on comparator): Long-term adverse events, including injection-site reactions, are reported in humans, but without a placebo comparison in the extension.
PLS-00107: eligible · indirect evidence (differs on outcome): The trial is a placebo-controlled RCT reporting adverse events with elamipretide, although only a narrative tolerability summary is available.
PLS-00108: not eligible (insufficient data)
PLS-00109: not eligible (insufficient data)
PLS-00110: not eligible (wrong outcome)
PLS-00111: eligible · indirect evidence (differs on outcome): Placebo-controlled human trial reporting safety and tolerability. However, the infusions were intravenous over only 5 days, and specific adverse events and discontinuations are not reported.
PLS-00112: not eligible (insufficient data)
PLS-00113: eligible · indirect evidence (differs on comparator): Reports adverse events, injection-site reactions and discontinuations with elamipretide in humans, but there is no placebo comparator.
PLS-00114: eligible · indirect evidence (differs on comparator): Reports adverse events, an injection-site reaction and discontinuations in humans given elamipretide, but has no placebo comparator.
PLS-00115: eligible · indirect evidence (differs on outcome): This is a placebo-controlled human trial of elamipretide reporting drug-related adverse event rates. Injection-site reactions and discontinuations are not specifically reported.
PLS-00116: eligible · direct evidence: The placebo-controlled trial reports adverse events with elamipretide, including injection site reactions and the absence of serious adverse events.
PLS-00117: eligible · direct evidence: This randomized placebo-controlled trial in humans gave intravenous elamipretide (MTP-131) and reports that it was safe and well tolerated, but the abstract gives no adverse event counts.
PLS-00118: not eligible (insufficient data)
PLS-00119: not eligible (not primary study)
PLS-00120: eligible · indirect evidence (differs on population, outcome): Placebo-controlled randomized human study of elamipretide reporting safety (no serious adverse events, stable vital signs), though only after a single infusion.
PLS-00121: not eligible (insufficient data)
PLS-00122: not eligible (insufficient data)
PLS-00123: not eligible (wrong outcome)
PLS-00124: not eligible (wrong outcome)
PLS-00125: not eligible (insufficient data)
PLS-00213: not eligible (insufficient data)
PLS-00216: not eligible (insufficient data)
PLS-00217: not eligible (insufficient data)
PLS-00218: not eligible (insufficient data)
PLS-00219: not eligible (insufficient data)
PLS-00220: not eligible (insufficient data)
PLS-00221: not eligible (insufficient data)
PLS-00222: not eligible (insufficient data)
PLS-00223: not eligible (not primary study)
PLS-00224: not eligible (insufficient data)
PLS-00228: eligible · indirect evidence (differs on intervention, population): This placebo-controlled study of elamipretide in humans registers safety and tolerability. The route is topical ophthalmic rather than injection, and no safety results are included in the record.
PLS-00229: not eligible (insufficient data)
PLS-00230: not eligible (insufficient data)
PLS-00231: not eligible (insufficient data)
PLS-00232: not eligible (insufficient data)
PLS-00233: not eligible (insufficient data)
PLS-00234: not eligible (insufficient data)
PLS-00236: not eligible (insufficient data)
PLS-00240: not eligible (insufficient data)
PLS-00241: not eligible (insufficient data)
PLS-00242: not eligible (insufficient data)
PLS-00244: not eligible (insufficient data)
PLS-00245: not eligible (insufficient data)
PLS-00250: not eligible (insufficient data)

Version history

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated by rule (no eligible human study was found), not reviewed by a person.

How claims are assessed

These assessments describe published research. Records marked automated were produced by AI under the published methodology and have not been reviewed by a person; they can contain errors. None of this is medical advice, not a statement about any product’s safety for human use, and not a regulatory approval. Peptide Library’s vendor and partner relationships play no part in them (editorial independence).