SS-31 / Elamipretide

ID: ss31_elamipretide

Aliases: elamipretide, MTP-131, Bendavia, FORZINITY, SS-31

Type: compound

Route/form: subcutaneous injection

Status: approved_accelerated_for_barth_syndrome

Evidence level: approved / labelled

Best data tier: approved label + human controlled/review

Support scope: human, non-human/mechanistic, review/regulatory

Source types: human_physiology, human_rct, human_rct_negative, label, mechanistic, regulatory_review

Linked sources: 7

Broad outcomes: Cardiovascular / lipids / blood pressure, Longevity / mitochondrial / redox, Muscle growth / performance / recovery

Reading note: These are curation notes anchored to linked sources, not a clinical recommendation or protocol.

Targets / mechanism

• mitochondrial cardiolipin interaction
• inner mitochondrial membrane/cristae stabilization hypothesis
• mitochondrial ATP production/coupling

Optimization domains

• mitochondrial
• cardiology
• rare disease
• Barth syndrome
• primary mitochondrial myopathy
• exercise tolerance
• aging

Research basis

• Mitochondrial cardiolipin-binding and membrane-mechanism data are better defined than many broad 'mitochondria peptides'.
• FDA accelerated approval in Barth syndrome, primary mitochondrial myopathy trials, and an older-adult ATP production study provide real human anchors.

Limits, risks, and missing evidence

• The approved context is Barth syndrome, not general performance, longevity, or mitochondrial optimization.
• Clinical results are mixed: the Barth randomized period and the MMPOWER-3 phase 3 PMM trial did not meet key endpoints, so general use should not be treated as established efficacy.

Risk flags

• accelerated approval
• rare disease context
• injection site reactions
• medical supervision
• unapproved context

Linked papers, labels, and reviews

1. DailyMed label: FORZINITY (elamipretide) injection
   label / dailymed_forzinity_label
   U.S. accelerated-approval label for Barth syndrome in patients weighing at least 30 kg.
2. FDA grants accelerated approval to first treatment for Barth syndrome
   regulatory_review / fda_forzinity_approval_2025
   FDA approval context and confirmatory-trial caveat for elamipretide.
3. Phase 2/3 randomized clinical trial and open-label extension of elamipretide in Barth syndrome
   human_rct / pubmed_elamipretide_barth_phase23_2020
   Randomized crossover Barth syndrome trial; primary endpoints were not met in the placebo-controlled part.
4. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy
   human_rct / pubmed_elamipretide_pmm_dose_2018
   MMPOWER phase 1/2 PMM trial; short IV dosing showed a dose-response signal on 6-minute walk distance while other endpoints were limited.
5. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
   human_rct_negative / pubmed_elamipretide_pmm_mmpower3_2023
   Phase 3 PMM trial; subcutaneous elamipretide was tolerated but did not improve 6MWT or fatigue endpoints versus placebo at 24 weeks.
6. In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial
   human_physiology / pubmed_elamipretide_older_muscle_atp_2021
   Randomized older-adult physiology study using 31P MRS ATPmax; supports a mitochondrial energetics signal, not a clinical performance protocol.
7. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics
   mechanistic / pubmed_ss31_bilayer_mechanism_2020
   Biophysical mechanism source for SS-31/elamipretide membrane and cardiolipin-linked activity.