FOR RESEARCH USE ONLY. NOT FOR HUMAN OR VETERINARY USE. NOT FOR HUMAN CONSUMPTION.
Compounds described on this site are supplied solely for laboratory research. They are not offered for human or veterinary use or for clinical use, and they are not intended to diagnose, mitigate, cure or prevent any disease.
Elamipretide, also known as SS-31 and MTP-131, is a synthetic tetrapeptide described as associating with cardiolipin on the inner mitochondrial membrane. The three publications reviewed are all human studies: a short acute study, a larger 28-day phase 2 trial, and a randomised crossover trial followed by an open-label extension. The acute finding was not reproduced in the larger trial and the crossover met neither primary endpoint; the U.S. FDA has approved a drug product containing elamipretide, but PepGenex research material is not that product.
At a glance
Also identified as
SS-31, MTP-131, Bendavia
Class
Mitochondria-targeting tetrapeptide
Target or mechanism
Cardiolipin (inner mitochondrial membrane)
Evidence types represented
human
Published studies reviewed
3
Regulatory and registry records
1
Last reviewed
2026-09-24
U.S. FDA status
An FDA approved drug product containing elamipretide (SS-31) exists. Source: Drugs@FDA, Application NDA 215244.
Overview
Elamipretide, also identified in the literature as SS-31 and as MTP-131, is a synthetic tetrapeptide described as associating with cardiolipin on the inner mitochondrial membrane.
The human record collected here has a shape worth reading in order. In 2017, a single dose in 36 adults with heart failure with reduced ejection fraction produced, at the highest amount, statistically significant reductions in left ventricular end-diastolic and end-systolic volume measured at the end of the exposure period. In 2020, a larger study gave 71 adults in the same condition elamipretide in one of two arms, or placebo, for 28 days and recorded no significant change in left ventricular end-systolic volume or ejection fraction against placebo.
The same pattern repeats in the Barth syndrome work. A randomised crossover trial in 12 participants met neither of its primary endpoints. The open-label extension that followed — everyone receiving the compound, no placebo group, eight participants reaching week 36 — reported improvement on one of them.
Both halves of both stories are on this page, and the tables keep them apart.
Regulatory status
An FDA approved drug product containing elamipretide (SS-31) exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
Described in the publications as a tetrapeptide that interacts with cardiolipin on the inner mitochondrial membrane. The Barth syndrome work states that mechanism explicitly; the heart failure studies measured cardiac structure and function rather than the mechanism itself.
Scope of the published work
Areas investigated
Left ventricular volumes and ejection fraction
Six-minute walk distance in Barth syndrome
Symptom assessment in Barth syndrome
Models used
Randomised human studies
Randomised crossover trial
Open-label extension
The acute finding recorded here was not reproduced by the larger 28-day study that followed it, and the randomised half of the Barth syndrome trial met neither primary endpoint. The favourable week 36 figures come from an open-label extension with no comparison group. Nothing on this page is a statement about the research material PepGenex supplies.
Limitations
Evidence represented on this page: human. No in vitro or animal research is represented. The page reviews 3 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Common questions
What is Elamipretide (SS-31)?
Elamipretide, also identified in the literature as SS-31 and as MTP-131, is a synthetic tetrapeptide described as associating with cardiolipin on the inner mitochondrial membrane.
How does Elamipretide (SS-31) work, according to the published research?
Described in the publications as a tetrapeptide that interacts with cardiolipin on the inner mitochondrial membrane. The Barth syndrome work states that mechanism explicitly; the heart failure studies measured cardiac structure and function rather than the mechanism itself.
What has published research on Elamipretide (SS-31) found, and what are its limits?
This page records 3 publications, reporting human work in 3. Each is listed with its identifier under References.
Human studies represented: Daubert et al., 2017, PMID 29217757; Reid et al., 2021, PMID 33077895; Butler et al., 2020, PMID 32068002.
Evidence represented on this page: human.
No in vitro or animal research is represented.
The page reviews 3 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
The acute finding recorded here was not reproduced by the larger 28-day study that followed it, and the randomised half of the Barth syndrome trial met neither primary endpoint. The favourable week 36 figures come from an open-label extension with no comparison group. Nothing on this page is a statement about the research material PepGenex supplies.
Is Elamipretide (SS-31) approved by the U.S. FDA?
An FDA approved drug product containing elamipretide (SS-31) exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
What risks have published studies of Elamipretide (SS-31) reported?
2 published human studies on this page report adverse events or safety measurements. Each is listed with its publication in the adverse-events section of this page.
Trial events do not establish a complete safety profile.
What adverse events have been reported in published studies of Elamipretide (SS-31)?
Adverse events and safety measurements as reported by the published human studies on this page. Each entry is attributed to its publication.
Daubert et al., 2017, PMID 29217757
Design and population
Double-blind, placebo-controlled, ascending-amount study in adults with heart failure with reduced ejection fraction (ejection fraction 35% or below). Three active cohorts of 8 each received a single dose; 12 received placebo. Assessments were made before, during and at the end of the exposure period, and at 6, 8, 12 and 24 hours after it started.
Events reported
There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts, and peak plasma concentrations occurred at the end of the exposure period and were undetectable 24 hours after it started.
Butler et al., 2020, PMID 32068002
Design and population
Phase 2, double-blind, placebo-controlled study. 71 adults with heart failure with reduced ejection fraction (ejection fraction 40% or below) were randomised 1:1:1 to placebo or to one of two elamipretide arms for 28 days, with left ventricular end-systolic volume assessed by cardiac magnetic resonance imaging.
Events reported
Rates of adverse events related to the study material were similar across the three groups.
Trial events do not establish a complete safety profile.
Published research
Grouped by the kind of study. Select one to narrow what is shown below.
Human phase 1(1)
Human phase 1n = 36
Daubert et al., 2017 (title withheld on this site; see the publication record)
Daubert MA, Yow E, Dunn G, et al., Circulation: Heart Failure, 2017;10(12):e004389
published
Double-blind, placebo-controlled, ascending-amount study in adults with heart failure with reduced ejection fraction (ejection fraction 35% or below). Three active cohorts of 8 each received a single dose; 12 received placebo. Assessments were made before, during and at the end of the exposure period, and at 6, 8, 12 and 24 hours after it started.
Left ventricular end-diastolic volume, difference against placebo
Randomised, controlled · End of exposure period · Adults with heart failure with reduced ejection fraction · vs Placebo
Arm
Reported
highest-dose cohort
-18 mL (P = 0.009)
Left ventricular end-systolic volume, difference against placebo
Randomised, controlled · End of exposure period · Adults with heart failure with reduced ejection fraction · vs Placebo
Arm
Reported
highest-dose cohort
-14 mL (P = 0.005)
There were no serious adverse events. Blood pressure and heart rate remained stable in all cohorts, and peak plasma concentrations occurred at the end of the exposure period and were undetectable 24 hours after it started.
The publication states its own limit plainly: it was the first study of this compound in heart failure with reduced ejection fraction, and further study was needed to establish longer-term safety and whether the changes it recorded persist.
What this study establishes
A single dose, at the highest of three amounts, was followed by smaller left ventricular volumes at the end of that exposure period than in the placebo group. The comparison is real and the p-values are the publication's own. What it describes is a change measured in the hours around one dose, in eight people.
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
Reid Thompson W, Hornby B, Manuel R, et al., Genetics in Medicine, 2021;23(3):471-478
published
The publication describes a phase 2/3 randomised, double-blind, placebo-controlled crossover trial followed by an open-label extension, in Barth syndrome. In part 1, 12 participants were randomised to elamipretide or placebo for 12 weeks, then a 4-week washout, then 12 weeks on the opposite arm. Ten continued into part 2, the open-label extension, with eight reaching week 36. The primary endpoints were the six-minute walk test and a Barth syndrome symptom assessment scale.
Six-minute walk test, change from baseline
Open-label extension — no placebo group · Week 36 · Open-label extension participants (8 of 10 reached week 36)
No comparison group. Everyone measured here received the compound, so the change recorded is not measured against anything. Figures from this part of a study cannot be read alongside figures from its randomised part.
Arm
Reported
open-label extension
+95.9 m (p = 0.024)
In part 1 — the randomised, placebo-controlled crossover — neither primary endpoint was met.
The publication also reports improvements at week 36 of the open-label extension on symptom-assessment endpoints including knee extensor strength, a participant global impression of symptoms, and some cardiac measures. No comparison group existed in this part of the trial, and specific values for those endpoints are not reproduced here.
Limitations
The two parts of this trial are two different kinds of evidence and the difference is the whole of what they mean. Part 1 compared the compound against placebo in the same participants and met neither of its primary endpoints. Part 2 gave everyone the compound, kept no comparison group, and ran to week 36 with eight participants — so the improvement it reports has nothing to be measured against, and it cannot be read as the result part 1 was looking for.
Butler et al., 2020 (title withheld on this site; see the publication record)
Butler J, Khan MS, Anker SD, et al., Journal of Cardiac Failure, 2020;26(5):429-437
published
Phase 2, double-blind, placebo-controlled study. 71 adults with heart failure with reduced ejection fraction (ejection fraction 40% or below) were randomised 1:1:1 to placebo or to one of two elamipretide arms for 28 days, with left ventricular end-systolic volume assessed by cardiac magnetic resonance imaging.
Left ventricular end-systolic volume, difference of means against placebo
Randomised, controlled · Week 4 · Adults with heart failure with reduced ejection fraction · vs Placebo
Arm
Reported
Lower dose
-0.3 mL (95% CI -4.6 to 4.0; P = 0.90)
Higher dose
+2.3 mL (95% CI -1.9 to 6.5; P = 0.28)
No significant differences in change in left ventricular end-systolic volume or in ejection fraction were observed between placebo and either elamipretide group. The publication's stated conclusion is that the compound was well tolerated but did not improve left ventricular end-systolic volume at four weeks.
Rates of adverse events related to the study material were similar across the three groups.
Context
This is the study that followed the 2017 single-dose work, and it is the reason that work cannot be read on its own. It was larger — 71 participants against 36 — it ran for 28 days rather than a single dose, and on left ventricular end-systolic volume it found no significant difference from placebo at either amount, with ejection fraction unchanged as well. An early favourable signal that a bigger and longer study does not reproduce is a normal event in research, and a record of the research has to show both.
Classification, structure, recorded targets, evidence types and FDA status only, each read from the two compounds' own pages. These comparisons do not compare study results.
Peptides studied in mitochondrial research: one synthetic and recorded at cardiolipin, one encoded in mitochondrial DNA.
Elamipretide (SS-31)
MOTS-c
Classification
Mitochondria-targeting tetrapeptide
Mitochondrial-derived peptide
Structure
Formula C32H49N9O5
Formula C101H152N28O22S2
Targets recorded
Cardiolipin (inner mitochondrial membrane)
No target recorded on its page
Evidence types represented
human
in vitro, animal
Status with the U.S. FDA
An FDA approved drug product containing elamipretide (SS-31) exists. Source: Drugs@FDA, Application NDA 215244.
Not shown (no Drugs@FDA application record verified for this page)
References
Published studies reviewed (3)
Daubert et al., 2017 (title withheld on this site; see the publication record) — Daubert MA, Yow E, Dunn G, et al., Circulation: Heart Failure, 2017;10(12):e004389
DOI 10.1161/CIRCHEARTFAILURE.117.004389 · PMID 29217757 · NCT02388464
Butler et al., 2020 (title withheld on this site; see the publication record) — Butler J, Khan MS, Anker SD, et al., Journal of Cardiac Failure, 2020;26(5):429-437
DOI 10.1016/j.cardfail.2020.02.001 · PMID 32068002
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 — Reid Thompson W, Hornby B, Manuel R, et al., Genetics in Medicine, 2021;23(3):471-478
DOI 10.1038/s41436-020-01006-8 · PMID 33077895 · PMC7935714 · NCT03098797
