At a glance

Mechanism of action

SS-31 (Elamipretide) binds specifically to cardiolipin in the inner mitochondrial membrane, stabilises the membrane folds (cristae), restores ATP production and cuts the output of reactive oxygen species (ROS).

Benefits & use

Said to reactivate cellular energy production in chronic fatigue, mitochondrial myopathies and age-related decline; the heart and kidneys benefit most.

Study status

Level 4: FDA Accelerated Approval on 19 Sept 2025 as FORZINITY (elamipretide) to improve muscle strength in Barth syndrome (≥ 30 kg). First approved mitochondria-targeted therapeutic ever; a confirmatory Phase 3 trial is required. Built on the TAZPOWER Phase 2/3 study and a 168-week open-label extension. Additional trials in dry AMD, primary mitochondrial myopathy (MMPOWER-3 post hoc, 2024) and heart failure. Consistently favourable safety profile.

Dosing note

Approved dose (FORZINITY): 40 mg subcutaneously once daily in patients ≥ 30 kg - as a ready-to-use solution, no reconstitution needed. The older research-chemical regimens (e.g. 500-1,000 mcg reconstituted in BAC water) are NOT the approved drug. No dosing instruction - information per FDA label only.

Important update (09/2025): On 19 September 2025 the FDA granted Accelerated Approval to FORZINITY (elamipretide) - the first mitochondria-targeted drug ever approved - to improve muscle strength in patients with Barth syndrome weighing at least 30 kg. Evidence level therefore rises from 3 to 4.

How does SS-31 work?

SS-31 (elamipretide, formerly coded Bendavia / MTP-131) is a small, cell-permeable peptide with an alternating aromatic-cationic structure. It binds selectively to cardiolipin, a phospholipid found exclusively in the inner mitochondrial membrane, and thereby stabilises the cristae. The FDA label summarises the mechanism as: “mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function.”

Unlike MOTS-c, which mainly targets mitochondrial gene expression and glucose metabolism, SS-31 works purely structurally: it repairs membrane geometry, lowers reactive oxygen species (ROS) output and restores ATP synthesis.

What is SS-31 used for?

Approved: FORZINITY 40 mg s.c. once daily in genetically confirmed Barth syndrome (≥ 30 kg).
In trials: primary mitochondrial myopathy (MMPOWER-3 post-hoc, 2024), dry age-related macular degeneration with geographic atrophy (ReCLAIM-2), chronic heart failure.

What does the evidence say?

The pivotal TAZPOWER trial (Phase 2/3, crossover, n = 12) narrowly missed its primary endpoints (6-minute walk test, fatigue score); in the 168-week open-label extension, however, 8 of 10 patients showed a clinically meaningful improvement in knee extensor strength and 6-minute walk distance (mean +96 m vs. baseline) together with increased cardiac stroke volume. On this basis the FDA Cardiovascular and Renal Drugs Advisory Committee voted 10:6 (Oct 2024) that elamipretide is effective, and FDA granted Accelerated Approval in September 2025. A confirmatory Phase 3 trial is a condition of continued approval.

Pharmacokinetics (FORZINITY label)

Dose-proportional exposure over 2-80 mg s.c., minimal accumulation
Tmax 0.5-1 h, s.c. bioavailability ≈ 92 %
Volume of distribution ≈ 0.5 L/kg, plasma protein binding ≈ 39 %
Metabolism: sequential C-terminal degradation to inactive metabolites M1 (tripeptide) and M2 (dipeptide); complete renal elimination within 48 h

Safety

Consistently favourable tolerability across trials. Contraindication: serious hypersensitivity to elamipretide or any excipient. Dose adjustment is required in severe renal impairment (eGFR < 30 mL/min, not on dialysis).

Note on research-chemical SS-31

Online sources still sell lyophilised “SS-31 peptide” for reconstitution in BAC water at microgram doses. This is not the approved medicinal product FORZINITY (ready-to-use 40 mg injection). For therapy, only the prescription product FORZINITY is relevant.

SS-31