Did the SS-31 phase 3 trial work?

No. MMPOWER-3, published in Neurology in 2023, tested elamipretide in primary mitochondrial myopathy and did not meet its primary endpoints.

What about the genotype analysis that found an effect?

It is a post-hoc analysis of the trial that missed its endpoints. Subgroup analyses after a negative trial generate hypotheses for a new prospective study; they do not turn a missed endpoint into a met one, and no confirmatory trial has been published.

How does SS-31 reach mitochondria?

By binding cardiolipin, a phospholipid found almost nowhere else in the cell. It finds its compartment through a lipid rather than through a receptor, which is an unusual targeting mechanism.

Is SS-31 the same as elamipretide?

Yes. SS-31 is the Szeto-Schiller series designation; elamipretide is the development name, and it has also appeared as MTP-131 and Bendavia.

Is SS-31 an approved medicine?

It holds no marketing authorisation for the indication its phase 3 trial tested. It is supplied here as a laboratory reagent for research use only.

Research guides

SS-31 (elamipretide): what the research says

One of very few compounds here to reach phase 3. The MMPOWER-3 trial missed its primary endpoints, and that result is the most useful thing it has.

Available in the catalogue

Supplied as research material. Sizes and pricing are on the product page. Availability is not a statement about what a compound does.

SS-31
Longevity & Cellular

SS-31 has a large, well-funded clinical development programme behind it, which makes it one of the best-evidenced compounds in this catalogue. What that programme found is not what most summaries of the molecule report.

What the molecule is

A synthetic tetrapeptide, D-Arg-Dmt-Lys-Phe-NH₂, from the Szeto-Schiller series developed at Weill Cornell. It is published as elamipretide, MTP-131 and Bendavia.

The mechanism is unusually specific

It concentrates in the inner mitochondrial membrane by binding cardiolipin, a phospholipid found almost nowhere else in the cell. Cardiolipin organises the proteins of the respiratory chain, and published work reports that binding it alters the membrane's surface charge and improves the efficiency of energy production in damaged mitochondria.

That is a genuinely distinctive targeting mechanism — the molecule finds its compartment by binding a lipid unique to it, rather than by engaging a receptor.

The phase 3 result

MMPOWER-3 was a randomised clinical trial in individuals with primary mitochondrial myopathy, published in Neurology in 2023. It did not meet its primary endpoints. An earlier randomised crossover study had reported signals worth pursuing, and a later post-hoc analysis examined whether effects differed by genotype — which is the standard and legitimate response to a failed trial, and also the standard way a failed trial gets reported as a qualified success.

The honest reading: a distinctive mechanism, extensive preclinical support, a large randomised trial in the target population, and a negative primary result. Post-hoc genotype analyses generate hypotheses; they do not convert a missed endpoint into a met one.

A negative phase 3 is more informative about a compound than a shelf of positive mechanism papers. It is also the part that disappears from most descriptions of this molecule, which is why it is stated here at length.

What studies reported

Each entry states what a study examined and the model it used. Nothing below describes an outcome for a person.

Everything below is drawn from published research, and each entry names the model the study used. Approval status varies by compound and by country, and nothing described here is supplied as a medicine or for use in a person.

Mitchell et al. (2020)Journal of Biological Chemistry · 295(21):7452–69
Reported that the peptide binds lipid bilayers and modulates surface electrostatics, proposed as a key part of its mechanism.
in vitro, lipid bilayers Source
Karaa et al. (2020)Journal of Cachexia, Sarcopenia and Muscle · 11(4):909–18
A randomised crossover trial in adults with primary mitochondrial myopathy, reporting the signals that supported progression to a larger trial.
human, randomised crossover trial Source

Adverse and null findings reported

Harms, tolerability observations, and trials that did not meet their endpoint. A negative result is a finding and is listed here rather than omitted.

Karaa et al. (2023)Neurology · 101(3):e238–52
Tested efficacy and safety in individuals with primary mitochondrial myopathy. The trial did not meet its primary endpoints — a negative result in the target population from the largest randomised study of this compound.
human, randomised clinical trial (MMPOWER-3) Source
Karaa et al. (2024)Orphanet Journal of Rare Diseases · 19(1):431
A post-hoc analysis examining whether effects differed by genotype within the trial that had missed its primary endpoints. Hypothesis-generating rather than confirmatory.
human, post-hoc analysis of MMPOWER-3 Source

What the research does not establish

An absence cannot be cited, so these are stated plainly. They are the part of the picture that silence would otherwise hide.

The compound has no marketing authorisation for the indication MMPOWER-3 tested. A phase 3 that misses its primary endpoints is the clearest evidence available about a compound and it should not be read past.
The post-hoc genotype analysis is hypothesis-generating. Subgroup findings from a trial that missed its endpoint require a new prospective trial to mean anything, and none has been published.
The mechanistic literature — cardiolipin binding, membrane electrostatics, respiratory chain efficiency — is strong and largely in vitro. A strong mechanism that fails in a clinical trial is a common pattern and not a contradiction.
Everything human is in primary mitochondrial myopathy or related conditions. Nothing published supports reading the results across to healthy people or to other conditions.
Long-term safety data outside the trial programme has not been published.

Common questions

Did the SS-31 phase 3 trial work?: No. MMPOWER-3, published in Neurology in 2023, tested elamipretide in primary mitochondrial myopathy and did not meet its primary endpoints.
What about the genotype analysis that found an effect?: It is a post-hoc analysis of the trial that missed its endpoints. Subgroup analyses after a negative trial generate hypotheses for a new prospective study; they do not turn a missed endpoint into a met one, and no confirmatory trial has been published.
How does SS-31 reach mitochondria?: By binding cardiolipin, a phospholipid found almost nowhere else in the cell. It finds its compartment through a lipid rather than through a receptor, which is an unusual targeting mechanism.
Is SS-31 the same as elamipretide?: Yes. SS-31 is the Szeto-Schiller series designation; elamipretide is the development name, and it has also appeared as MTP-131 and Bendavia.
Is SS-31 an approved medicine?: It holds no marketing authorisation for the indication its phase 3 trial tested. It is supplied here as a laboratory reagent for research use only.

Compounds covered

The reference page for each compound this article discusses.

SS-31

ARA-290 (cibinetide): what the research says
An erythropoietin fragment engineered to keep the tissue protection and drop the red-cell activity, with a published randomised trial in type 2 diabetes.
MOTS-c: what the research says
A peptide encoded in mitochondrial rather than nuclear DNA, whose discovery mattered more than the molecule. The founding mouse work, and the ten years since.
Peptide shelf life and stability
How long lyophilised and reconstituted peptides keep, and the four things that shorten it: temperature, moisture, light and oxidation. Storage figures included.

About this article

Everything reported here comes from published research, and each finding names the model the study used — cell culture, rat, or human. Findings in one model do not transfer to another, most of the work described is preclinical, and none of it is a claim that a compound is safe or effective for any purpose. Nothing on this page describes doses, routes of administration, or use in a person.

Approval status varies by compound and by country. A few of the substances described are the active ingredient of medicines authorised in the EU; most have no marketing authorisation anywhere and have never been assessed by a regulator. Neither is supplied as a medicine here. All material supplied by ASSAY is sold for in-vitro laboratory research only, and is not a drug, food, cosmetic or medical device, and not for human or veterinary use.

All guides