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Ela3.0
Elamipretide Research
Mostly mechanism / observationalLimited safety
12 peer-reviewed studies
What the evidence says
Mostly mechanism / observational
Most Elamipretide studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from medium-quality meta-analyses and randomised trials published 2016–2025 with a typical study size of 30 participants.
Based on 12 studies · 1 meta-analysis · 5 RCTs · 340 total participants
Confidence
Moderate
By outcome
Mitochondrial disease & myopathy
Mostly mechanism / observational7 studies
Cardiac & reperfusion
Mostly mechanism / observational6 studies
Energy & fatigue
Mostly mechanism / observational5 studies
Safety profile
Mostly mechanism / observational3 studies
Vision & eye health
Too few graded studies1 study
Active research area
8 studies in the last 5 years · Latest meta-analysis: 2022
20162025
1RCTn=218 · medium study2023
This study provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks compared with placebo in patients with primary mitochondrial myopathy.
Karaa A, Bertini E, Carelli V, Cohen BH, Enns GM, Falk MJ, et al. · Neurology (2023)
Pivotal Phase 3, double-blind, placebo-controlled trial (N=218; 109 elamipretide, 109 placebo) of 40 mg/d subcutaneous elamipretide for 24 weeks
MISSED both co-primary endpoints: change in 6-minute walk distance and total fatigue on the PMMSA
Genotypically diverse population (74% mtDNA, 26% nDNA defects); the trial did not demonstrate a significant overall benefit
Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by CK-MB AUC over 72 h, nor with improvement in prespecified MRI, angiographic, electrocardiographic, or clinical outcomes.
Gibson CM, Giugliano RP, Kloner RA, Bode C, Tendera M, Jánosi A, et al. · Eur Heart J (2016)
Multicentre, randomized, double-blind Phase 2a trial of IV MTP-131 (elamipretide) vs placebo during primary PCI for first anterior STEMI
FAILED its primary endpoint: no reduction in infarct size (CK-MB AUC over 72 h)
No improvement in any prespecified imaging, angiographic, ECG, or clinical outcome
[The 6MWT distance was greater with elamipretide than] the placebo-treated group, a difference of 19.8 m (95% confidence interval, -2.8, 42.5; P = 0.0833).
Karaa A, Haas R, Goldstein A, Vockley J, Cohen BH, et al. · J Cachexia Sarcopenia Muscle (2020)
MMPOWER-2: randomized, double-blind, placebo-controlled crossover (N=30), 40 mg/day subcutaneous for 4 weeks per period
Primary 6-minute walk endpoint was NOT statistically significant (19.8 m difference, P=0.0833)
Subjective fatigue measures (PMMSA, Neuro-QoL) did improve significantly
While short-term studies indicate that mitoAOXs are generally well tolerated, there is currently limited evidence to support the use of mitoAOXs in the management of glycaemic control and cardiovascular health.
Mason SA, Wadley GD, Keske MA, Parker L. · Diabetes Obes Metab (2022)
Systematic review and meta-analysis of 19 RCTs (n=884) of mitochondrial-targeted antioxidants — Elamipretide, MitoQ and MitoTEMPO — searched through June 2021
Pooled mitoAOXs significantly improved brachial flow-mediated dilation (3 trials; SMD 1.19, 95% CI 0.28-2.16) but with very-low evidence certainty; no significant effect on any glycaemic, cardiovascular or oxidative-stress outcome
Subcutaneous elamipretide specifically increased mild-to-moderate injection-site events; no serious treatment-emergent adverse events across mitoAOXs
Post hoc analyses indicated that elamipretide had a beneficial effect in PMM patients with mtDNA replisome disorders, underscoring the importance of considering specific genetic subtypes in PMM clinical trials.
Karaa A, Bertini E, Carelli V, Cohen B, Enns GM, Falk MJ, et al. · Orphanet J Rare Dis (2024)
Post-hoc genotype analysis of the negative MMPOWER-3 trial
Subjects with nuclear-DNA (replisome, e.g. POLG/TWNK) variants showed a 6MWT improvement trending toward significance (25.2 vs 2.0 m; P=0.06)
Subjects with mtDNA variants (74% of the trial) showed no difference vs placebo
A single infusion of elamipretide is safe and well tolerated; high-dose elamipretide resulted in favorable changes in left ventricular volumes that correlated with peak plasma concentrations.
Daubert MA, Yow E, Dunn G, Marchev S, Barnhart H, Douglas PS, et al. · Circ Heart Fail (2017)
Double-blind, placebo-controlled, ascending-dose trial of a single 4-hour infusion in HFrEF (EF ≤35%); N=36 (three elamipretide dose cohorts of 8 plus 12 placebo)
Primary finding: safety and tolerability — the drug was safe and well tolerated
Only an exploratory, dose-related change in left-ventricular volumes at the highest dose; no efficacy endpoint was met
Significant improvements from open-label-extension baseline on the 6-minute walk test occurred at all time points (cumulative 96.1 m of improvement at week 168), with sustained tolerability.
Thompson WR, Manuel R, Abbruscato A, Carr J, Campbell J, Hornby B, et al. · Genet Med (2024)
168-week open-label extension of the TAZPOWER trial in Barth syndrome; only 10 patients entered and 8 reached week 168
Reported sustained 6-minute-walk improvement (cumulative 96.1 m), reduced fatigue, and improved 3D LV volumes
Cardiolipin/monolysocardiolipin biomarkers improved, correlating with clinical outcomes
For the 6-minute walk test, the least-squares mean difference between elamipretide-treated patients and natural-history controls was 79.7 m (P = 0.0004) at week 64.
Hornby B, Thompson WR, Almuqbil M, Manuel R, Abbruscato A, Carr J, et al. · Orphanet J Rare Dis (2022)
Phase 3 observational, retrospective study comparing 8 TAZPOWER open-label-extension patients with 19 untreated natural-history controls via propensity scoring
Reported significant 6MWT and muscle-strength advantages for elamipretide and increased LV stroke volume
Designed to bolster the open-label efficacy signal because the randomized trial portion was not conclusive
Elamipretide seems to be well tolerated without serious AEs in patients with dry AMD and NCGA. Exploratory analyses demonstrated possible positive effect on visual function, particularly under low luminance.
SS-31 effectively alleviated these pathological changes and exhibited significant efficacy in ameliorating mitochondrial dysfunction, such as by promoting adenosine triphosphate generation, improving mitochondrial membrane potential and restoring the mitochondrial ultrastructure.
Xiong L, Hu H, Zhu F, Shi H, Fan X, Pan S, et al. · Int J Mol Med (2024)
Preclinical study in high-glucose-treated H9C2 cardiomyocytes and a diabetic-cardiomyopathy mouse model
SS-31 improved ATP generation, mitochondrial membrane potential, and ultrastructure, and reduced mitochondria-dependent ferroptosis
Mechanistically links cardiolipin protection to anti-ferroptotic mitoGPX4 activation