SS-31 (elamipretide)

Elamipretide is FDA approved as Forzinity for a narrow Barth syndrome indication under accelerated approval. That does not validate general mitochondrial, anti-aging, heart-failure, or eye-disease use.

Cardiolipin-binding cell-penetrating tetrapeptide

Also called elamipretide
FDA brand name Forzinity
Accelerated approval is limited to Barth syndrome patients weighing at least 30 kg

Who is Forzinity approved for?

FDA granted accelerated approval to Forzinity on September 19, 2025 to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg. It is administered once daily by subcutaneous injection.

The approval does not cover fatigue, aging, athletic recovery, heart failure, macular degeneration, or general mitochondrial health.

Forzinity approval · Barth syndrome

FDA approval announcement

U.S. Food and Drug Administration, September 19, 2025

FDA describes the narrow indication, surrogate endpoint, accelerated-approval basis, and required confirmatory evidence.

Participants / model: Adults and children with Barth syndrome weighing at least 30 kg
Treatment: Once-daily subcutaneous elamipretide
Follow-up: Continued use under an accelerated approval
Study design: Regulatory action based on integrated evidence

Accelerated approval means clinical benefit remains to be confirmed.

Read the original source

Forzinity label · use and safety

FDA label

Stealth BioTherapeutics; U.S. FDA, 2025

Defines the indication, weight threshold, subcutaneous administration, hypersensitivity warning, benzyl-alcohol warning, and common injection-site reactions.

Participants / model: Barth syndrome patients weighing at least 30 kg
Treatment: Forzinity subcutaneous injection
Follow-up: Chronic labeled use
Study design: FDA-approved prescribing information

The label does not authorize other mitochondrial or aging indications.

Read the original source

What endpoint supported accelerated approval, and what remains unconfirmed?

The 12-person randomized crossover phase did not beat placebo on its two primary endpoints, six-minute walk distance and fatigue score, and did not show a significant knee-strength difference. FDA's accelerated approval relied on knee-extensor strength increases observed later in the open-label extension, treating that measure as reasonably likely to predict benefit.

All 12 participants were male. Ten entered the open-label extension and eight remained through week 168. Median knee-strength change was -5 newtons on placebo and +4 newtons on Forzinity during the randomized period, then +34 newtons at extension week 12, +41 at week 48, and +63 among eight participants at week 168. With no concurrent control in the extension, natural history, selection, and time effects remain unresolved.

Forzinity approval · Barth syndrome

FDA approval announcement

U.S. Food and Drug Administration, September 19, 2025

FDA describes the narrow indication, surrogate endpoint, accelerated-approval basis, and required confirmatory evidence.

Participants / model: Adults and children with Barth syndrome weighing at least 30 kg
Treatment: Once-daily subcutaneous elamipretide
Follow-up: Continued use under an accelerated approval
Study design: Regulatory action based on integrated evidence

Accelerated approval means clinical benefit remains to be confirmed.

Read the original source

FDA snapshot · randomized failure and open-label strength

FDA trial review summary

U.S. Food and Drug Administration, 2025

FDA reports that the 12-person randomized phase was not superior to placebo on six-minute walk distance or fatigue and showed no significant knee-strength difference; descriptive strength increases appeared in the uncontrolled extension.

Participants / model: Twelve male participants aged 12 to 35 with genetically confirmed Barth syndrome
Treatment: Forzinity 40 mg subcutaneously daily and placebo in crossover, followed by open-label Forzinity
Follow-up: 12-week randomized periods and extension through 192 planned weeks; eight participants reached week 168
Study design: FDA summary of randomized crossover and single-arm extension evidence

The approval endpoint emerged in an open-label extension after the randomized primary endpoints failed.

Read the original source

Forzinity · confirmatory requirement

FDA postmarketing requirement table

U.S. Food and Drug Administration.

Lists Forzinity's required randomized confirmatory study and target completion date.

Participants / model: Barth syndrome population specified by FDA
Treatment: Elamipretide versus placebo
Follow-up: Target completion March 31, 2030
Study design: Postmarketing requirement

The date is a regulatory target, not a result.

Read the original source

Did elamipretide work in heart failure or geographic atrophy?

Not in the principal randomized outcomes. PROGRESS-HF randomized 71 people with stable heart failure and reduced ejection fraction for 28 days and did not improve left-ventricular end-systolic volume or ejection fraction. ReCLAIM-2 randomized 176 people with geographic atrophy for 48 weeks and missed both co-primary outcomes.

ReCLAIM-2 missed both co-primary endpoints. Nominal secondary retinal-structure findings require confirmation and do not establish treatment benefit.

PROGRESS-HF · negative cardiac outcomes

Randomized trial

Butler et al., Journal of Cardiac Failure, 2020

In 71 participants, 28 days of elamipretide did not significantly improve the primary ventricular-volume outcome or ejection fraction versus placebo.

Participants / model: Stable heart failure with reduced ejection fraction
Treatment: Daily elamipretide infusion or placebo
Follow-up: 28 days
Study design: Randomized, double-blind, placebo-controlled trial

Short duration limits long-term conclusions, but the prespecified cardiac endpoints were negative.

Read the original source

ReCLAIM-2 · missed co-primary outcomes

Randomized trial

Metelitsina et al., Ophthalmology Science, 2024

The 176-person trial missed its co-primary low-luminance visual-acuity and geographic-atrophy-area outcomes; secondary ellipsoid-zone findings were nominal.

Participants / model: Adults with geographic atrophy from dry age-related macular degeneration
Treatment: Daily subcutaneous elamipretide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-masked, placebo-controlled phase 2 trial

Both co-primary endpoints failed; the nominal secondary structural findings require confirmation.

Read the original source

What safety issues matter for Forzinity?

The label warns that serious hypersensitivity reactions can occur minutes to months after starting treatment. It also warns about benzyl-alcohol toxicity in neonates and reports injection-site reactions as common adverse effects.

The small Barth syndrome population cannot characterize rare or long-term harms from broader off-label use.

Forzinity label · use and safety

FDA label

Stealth BioTherapeutics; U.S. FDA, 2025

Defines the indication, weight threshold, subcutaneous administration, hypersensitivity warning, benzyl-alcohol warning, and common injection-site reactions.

Participants / model: Barth syndrome patients weighing at least 30 kg
Treatment: Forzinity subcutaneous injection
Follow-up: Chronic labeled use
Study design: FDA-approved prescribing information

The label does not authorize other mitochondrial or aging indications.

Read the original source

What does cardiolipin binding establish in people?

Primary mechanistic work supports binding to cardiolipin and effects on mitochondrial membrane processes. It does not show that the drug ignores every healthy mitochondrion or that cardiolipin binding predicts benefit across unrelated diseases.

Cardiolipin binding was demonstrated preclinically, but efficacy differed across disease-specific randomized trials.

Elamipretide mechanism · cardiolipin

Preclinical mechanism study

Birk et al., Journal of the American Society of Nephrology, 2013

Experimental models support an interaction with cardiolipin and preservation of mitochondrial cristae and electron transport.

Participants / model: Cell and animal models
Treatment: Elamipretide exposure
Follow-up: Acute experimental studies
Study design: Preclinical mechanistic experiments

Preclinical binding and organelle findings do not establish selective clinical action or efficacy in people.

Read the original source

Is there direct human evidence for general longevity use?

The cited human evidence does not establish that claim. The FDA indication is Barth syndrome, while randomized studies tested Barth syndrome, heart failure, and geographic atrophy. None establishes longer life, slower general aging, or benefit in healthy adults.

None of the cited human studies measured lifespan, mortality, or healthy-aging outcomes.

Forzinity label · use and safety

FDA label

Stealth BioTherapeutics; U.S. FDA, 2025

Defines the indication, weight threshold, subcutaneous administration, hypersensitivity warning, benzyl-alcohol warning, and common injection-site reactions.

Participants / model: Barth syndrome patients weighing at least 30 kg
Treatment: Forzinity subcutaneous injection
Follow-up: Chronic labeled use
Study design: FDA-approved prescribing information

The label does not authorize other mitochondrial or aging indications.

Read the original source

PROGRESS-HF · negative cardiac outcomes

Randomized trial

Butler et al., Journal of Cardiac Failure, 2020

In 71 participants, 28 days of elamipretide did not significantly improve the primary ventricular-volume outcome or ejection fraction versus placebo.

Participants / model: Stable heart failure with reduced ejection fraction
Treatment: Daily elamipretide infusion or placebo
Follow-up: 28 days
Study design: Randomized, double-blind, placebo-controlled trial

Short duration limits long-term conclusions, but the prespecified cardiac endpoints were negative.

Read the original source

ReCLAIM-2 · missed co-primary outcomes

Randomized trial

Metelitsina et al., Ophthalmology Science, 2024

The 176-person trial missed its co-primary low-luminance visual-acuity and geographic-atrophy-area outcomes; secondary ellipsoid-zone findings were nominal.

Participants / model: Adults with geographic atrophy from dry age-related macular degeneration
Treatment: Daily subcutaneous elamipretide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-masked, placebo-controlled phase 2 trial

Both co-primary endpoints failed; the nominal secondary structural findings require confirmation.

Read the original source

Studies and sources

FDA snapshot · randomized failure and open-label strength

FDA trial review summary

U.S. Food and Drug Administration, 2025

FDA reports that the 12-person randomized phase was not superior to placebo on six-minute walk distance or fatigue and showed no significant knee-strength difference; descriptive strength increases appeared in the uncontrolled extension.

Participants / model: Twelve male participants aged 12 to 35 with genetically confirmed Barth syndrome
Treatment: Forzinity 40 mg subcutaneously daily and placebo in crossover, followed by open-label Forzinity
Follow-up: 12-week randomized periods and extension through 192 planned weeks; eight participants reached week 168
Study design: FDA summary of randomized crossover and single-arm extension evidence

The approval endpoint emerged in an open-label extension after the randomized primary endpoints failed.

Read the original source

Forzinity approval · Barth syndrome

FDA approval announcement

U.S. Food and Drug Administration, September 19, 2025

FDA describes the narrow indication, surrogate endpoint, accelerated-approval basis, and required confirmatory evidence.

Participants / model: Adults and children with Barth syndrome weighing at least 30 kg
Treatment: Once-daily subcutaneous elamipretide
Follow-up: Continued use under an accelerated approval
Study design: Regulatory action based on integrated evidence

Accelerated approval means clinical benefit remains to be confirmed.

Read the original source

Forzinity label · use and safety

FDA label

Stealth BioTherapeutics; U.S. FDA, 2025

Defines the indication, weight threshold, subcutaneous administration, hypersensitivity warning, benzyl-alcohol warning, and common injection-site reactions.

Participants / model: Barth syndrome patients weighing at least 30 kg
Treatment: Forzinity subcutaneous injection
Follow-up: Chronic labeled use
Study design: FDA-approved prescribing information

The label does not authorize other mitochondrial or aging indications.

Read the original source

Forzinity · confirmatory requirement

FDA postmarketing requirement table

U.S. Food and Drug Administration.

Lists Forzinity's required randomized confirmatory study and target completion date.

Participants / model: Barth syndrome population specified by FDA
Treatment: Elamipretide versus placebo
Follow-up: Target completion March 31, 2030
Study design: Postmarketing requirement

The date is a regulatory target, not a result.

Read the original source

PROGRESS-HF · negative cardiac outcomes

Randomized trial

Butler et al., Journal of Cardiac Failure, 2020

In 71 participants, 28 days of elamipretide did not significantly improve the primary ventricular-volume outcome or ejection fraction versus placebo.

Participants / model: Stable heart failure with reduced ejection fraction
Treatment: Daily elamipretide infusion or placebo
Follow-up: 28 days
Study design: Randomized, double-blind, placebo-controlled trial

Short duration limits long-term conclusions, but the prespecified cardiac endpoints were negative.

Read the original source

ReCLAIM-2 · missed co-primary outcomes

Randomized trial

Metelitsina et al., Ophthalmology Science, 2024

The 176-person trial missed its co-primary low-luminance visual-acuity and geographic-atrophy-area outcomes; secondary ellipsoid-zone findings were nominal.

Participants / model: Adults with geographic atrophy from dry age-related macular degeneration
Treatment: Daily subcutaneous elamipretide or placebo
Follow-up: 48 weeks
Study design: Randomized, double-masked, placebo-controlled phase 2 trial

Both co-primary endpoints failed; the nominal secondary structural findings require confirmation.

Read the original source

Elamipretide mechanism · cardiolipin

Preclinical mechanism study

Birk et al., Journal of the American Society of Nephrology, 2013

Experimental models support an interaction with cardiolipin and preservation of mitochondrial cristae and electron transport.

Participants / model: Cell and animal models
Treatment: Elamipretide exposure
Follow-up: Acute experimental studies
Study design: Preclinical mechanistic experiments

Preclinical binding and organelle findings do not establish selective clinical action or efficacy in people.

Read the original source

Why is SS-31 (elamipretide) in A tier?

The A tier reflects accelerated approval for a narrow Barth syndrome indication. The pivotal 12-person randomized period missed its primary endpoints, benefit remains subject to confirmation, and trials in other diseases were negative.