SS-31 (Elamipretide): The Phase 3 Trial Missed Its Endpoints
SS-31 is a real drug in real trials for rare mitochondrial disease, not aging. Its largest controlled trial missed its primary endpoints. Vendors omit that.
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Plain English
SS-31, or elamipretide, is a mitochondria-targeted peptide being developed as a medicine for rare genetic mitochondrial diseases. It has a substantial trial programme, which is unusual here. Its largest controlled trial did not meet its primary endpoints. It is sold online as a longevity peptide to people who do not have those diseases.
- Genuinely in clinical development - 16 randomised trials on PubMed.
- The lead Phase 3 in mitochondrial myopathy did not improve its primary outcomes.
- No trial has tested it in healthy adults for aging or energy.
SS-31 is not one of the compounds we cover where the research is thin and the marketing is thick. The research is substantial. Pharmaceutical companies have run randomised, controlled, multicentre trials of this molecule in real patients.
That is exactly why the result deserves a page of its own — because the headline finding is not the one the vendors quote.
What it is
SS-31 is elamipretide. It concentrates in the inner mitochondrial membrane and interacts with cardiolipin, a lipid the machinery of energy production depends on. The proposition is that a peptide which stabilises that machinery could help in diseases where it is failing.
That is a serious idea, and it has been tested seriously.
Where it has been tested
The programme in primary mitochondrial myopathy ran through dose-escalation Karaa 2018 - Karaa A, Haas R, Goldstein A et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018;90(14):e1212-e1221. (opens PubMed in a new tab), a randomised crossover trial Karaa 2020 - Karaa A, Haas R, Goldstein A et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle. 2020;11(4):909-918. (opens PubMed in a new tab), and then the large controlled study Karaa 2023 - Karaa A, Bertini E, Carelli V et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252. (opens PubMed in a new tab). There is separate work in Barth syndrome Thompson 2024 - Thompson WR, Manuel R, Abbruscato A et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138. (opens PubMed in a new tab) and a topical ophthalmic formulation for an eye condition Karanjia 2024 - Karanjia R, Sadun AA. Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial. Ophthalmology. 2024;131(4):422-433. (opens PubMed in a new tab).
The result
The trial in primary mitochondrial myopathy reports that it did not meet its primary endpoints, assessing the six-minute walk test and total fatigue score, and states directly that subcutaneous elamipretide “did not improve outcomes” on those measures in those patients Karaa 2023 - Karaa A, Bertini E, Carelli V et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252. (opens PubMed in a new tab).
The more encouraging result, and its design
In Barth syndrome — an ultra-rare X-linked disorder — elamipretide was associated with sustained tolerability and with improvements in functional assessments and cardiac function Thompson 2024 - Thompson WR, Manuel R, Abbruscato A et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138. (opens PubMed in a new tab).
Read that alongside how it was produced. Those improvements come from an open-label extension: everyone knew who was receiving the drug, and there was no concurrent placebo group. That is a weaker design than the trial that failed, and in a condition affecting a tiny number of people worldwide.
It is a real signal worth following. It is not evidence that a healthy adult will feel more energetic.
Dose, and why we are not translating one
The trials administered subcutaneous elamipretide to patients with diagnosed mitochondrial disease, under clinical supervision, with monitoring.
We report doses where a study establishes one for the use in question. Here the studied doses belong to rare genetic disorders, and the largest of those trials did not show benefit on its primary outcomes. Carrying a number from that setting to a healthy adult buying a vial online would be inventing a translation the evidence does not support.
Status
US legal status - Research use only · not for human use
Sold for laboratory research use only. Not approved by the FDA for human use, and cannot be lawfully marketed as a supplement or a medicine. Products sold this way are not made to pharmaceutical quality standards, and their contents are not verified by anyone.
SS-31 is sold as a research chemical. That is the legal basis on which a vendor can sell it at all, and it means the contents of the vial are not verified by anyone — an odd position for a molecule that also exists as a carefully manufactured investigational medicine.
References
Bibliographic detail is fetched from PubMed, not written by us - so a citation here cannot drift from the paper it names. Study design comes from PubMed's own tags rather than our judgement.
- 1.Karaa A, Bertini E, Carelli V et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252.Randomised trialPMID 37268435full text
- 2.Thompson WR, Manuel R, Abbruscato A et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138.Randomised trialPMID 38602181
- 3.Karaa A, Haas R, Goldstein A et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018;90(14):e1212-e1221.Randomised trialPMID 29500292full text
- 4.Karaa A, Haas R, Goldstein A et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle. 2020;11(4):909-918.Randomised trialPMID 32096613full text
- 5.Karanjia R, Sadun AA. Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial. Ophthalmology. 2024;131(4):422-433.Randomised trialPMID 37923251