SS-31

FDA granted Forzinity (elamipretide) accelerated approval on September 19, 2025 to improve muscle strength in adults and children with Barth syndrome weighing at least 30 kg. Approval used knee-extensor strength as an intermediate endpoint and requires confirmation of clinical benefit. It does not approve research-market SS-31 products or performance and longevity uses.^[1][2]

Jurisdiction

United States

Product

FORZINITY (elamipretide) injection

Indication

Improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg

Record date

2026-09-08 · Approved 2025-09-19

• US product-specific approval; benefit outside the labeled population is not established.

SS-31 is also called elamipretide, a tetrapeptide that binds cardiolipin in the inner mitochondrial membrane. Forzinity is the approved elamipretide hydrochloride injection. Shared peptide names do not establish that research-market preparations have the same composition, quality or clinical effects as the approved product.^[2][3]

• Molecular identity and brand identity are distinct from authentication or equivalence of a third-party product.

Forzinity is contraindicated in people with a history of serious hypersensitivity to elamipretide or its excipients. Serious allergic reactions requiring emergency intervention have occurred, and injection-site reactions were common in the labeled trial. Human pregnancy and lactation data are lacking; neither is listed as an absolute contraindication.^[2]

• The label does not establish the safety of unapproved research-market preparations.

Forzinity contains benzyl alcohol. Its label warns of serious and potentially fatal toxicity in neonates from benzyl-alcohol-containing medicines and states that Forzinity is not approved for neonates or intravenous use. The historical neonatal events described in this warning involved other medicines.^[2]

• This excipient warning applies to the labeled formulation; it does not describe neonatal deaths in the elamipretide trial.

The Forzinity label reports eosinophil increases during longer treatment. Counts generally returned toward baseline during continued treatment or after discontinuation, without associated clinical manifestations or other laboratory abnormalities identified in the label.^[2]

• This observation does not establish comprehensive hematologic safety or a routine monitoring schedule.

Forzinity exposure increases with renal impairment. The label reports urinary elimination of elamipretide and its metabolites and provides a reduced regimen for adults with severe renal impairment who are not receiving dialysis. It does not provide a single elimination half-life applicable to all SS-31 products.^[2]

• Renal dosing and exposure findings are specific to the approved formulation; pediatric renal and dialysis regimens are not established.

The FDA review reports different parent-drug half-lives after a single studied 40 mg subcutaneous dose: a mean of 3.16 hours in 32 healthy participants and 1.48 hours in seven participants with Barth syndrome. These study-specific estimates are not a universal value for SS-31 products or a measure of how long a clinical effect lasts.^[8]

• Small, distinct pharmacokinetic cohorts and specific formulations; parent-drug estimates must not be conflated with metabolite half-lives or clinical duration.

In the 12-person randomized Barth syndrome crossover trial, elamipretide did not outperform placebo on walking distance or fatigue, and knee-extensor strength did not increase during randomized treatment. Separately, the 218-person MMPOWER-3 trial did not demonstrate superiority on walking distance or fatigue after 24 weeks in primary mitochondrial myopathy.^[2][3][4]

• Barth syndrome and primary mitochondrial myopathy populations are not interchangeable.
• MMPOWER-3 abstract/body fatigue statistics disagree; the null primary conclusion is consistent, and disputed precise statistics are omitted.

Knee-extensor strength increased during the uncontrolled Barth syndrome extension. Ten participants entered, and eight participated through 168 weeks. These descriptive changes lack a concurrent placebo comparison and do not establish the confirmed clinical benefit required after accelerated approval.^[2][1]

• Same small cohort as the randomized Barth trial; attrition, lack of blinding and effort-dependent testing limit causal inference.

A randomized single-infusion study reported on 39 treated healthy adults aged 60–85 selected for low muscle mitochondrial function. The absolute ATP-capacity comparison did not reach statistical significance, while a relative-change analysis did; there was no significant between-group ATP-capacity difference at day 7. Prespecified fatigue-resistance analyses were nonsignificant, while exploratory analyses reported positive muscle-performance signals. The study does not establish longevity or athletic benefits.^[5][6]

• Small selected older population, surrogate endpoint, amended primary outcome and short follow-up; not chronic SC treatment or healthy young athletes.
• The publication describes 39 randomized participants; the registry reports 41 randomized, two excluded before treatment and 39 treated/completed. Use the treated denominator and preserve the reporting discrepancy.

Later genotype and phenotype analyses of MMPOWER-3 reported walking-distance signals in selected nuclear-DNA disease subgroups. These exploratory and posthoc analyses used participants from the same trial, whose overall primary outcomes were null; they provide hypotheses for further trials rather than independent confirmation of benefit.^[7][4]

• Multiple small subgroup analyses, corrected genotype grouping and per-protocol selection limit inference. No corresponding differential fatigue benefit was established.

Elamipretide inhibits the MATE1 transporter in vitro. FDA required a clinical study with metformin to characterize the interaction after repeat Forzinity exposure. The in-vitro finding and study requirement do not establish the size or clinical consequences of an interaction.^[2][1]

• Clinical interaction results were not verified in this bounded review; no pair-level safety or harm classification is implied.