SS-31 (Elamipretide)
Elamipretide (also known as MTP-131, Bendavia; trade name Forzinity)
SS-31 (elamipretide) is a cell-permeable, mitochondria-targeted tetrapeptide that selectively binds cardiolipin on the inner mitochondrial membrane, stabilizing cristae structure and improving bioenergetics. It received FDA accelerated approval in September 2025 as Forzinity for Barth syndrome (https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-first-treatment-barth-syndrome). While promising in preclinical models for various age-related and mitochondrial conditions, human clinical trials have yielded mixed results, including a failed Phase 3 trial for primary mitochondrial myopathy (DOI: 10.1212/WNL.0000000000207402).
Last updated: 2026-03-12
Safety Summary
No treatment-related serious adverse events or fatalities have been reported in clinical trials across all indications (DOI: 10.1212/WNL.0000000000207402). The ELViS-FA trial (NCT05168774, n=16) in Friedreich ataxia reported SAEs including aspiration pneumonia, acute perforated appendicitis, vasovagal episode, pneumonia, and pulmonary embolism, but these were assessed as likely related to underlying disease rather than study drug. Injection site reactions are the most common adverse events and are generally mild, self-limiting, and manageable with site rotation. Well-tolerated in open-label extensions up to 168 weeks (TAZPOWER OLE, PMID: 38602181). No abuse potential identified; not a controlled substance, Forzinity FDA label.
Known Side Effects
Very common (57-75% in clinical trials)
Very common (47-75% in clinical trials)
Common (20-38% in clinical trials)
Common (20-31% in clinical trials)
Common (10-63% across trials)
Common (10-30%)
Uncommon (1-10%)
Uncommon (1-10% clinical; more common in community reports at doses >5 mg)
Uncommon (<10%)
Who Should NOT Use This
Rare hypersensitivity reactions (rash, cough, shortness of breath) requiring discontinuation have been reported.
No human pregnancy data available. Avoid in pregnancy/breastfeeding per standard precautionary principle.
50% dose reduction recommended in severe renal impairment. Renal excretion is the primary elimination pathway. Not studied in dialysis patients.
Limited data in patients with severe cardiac conduction abnormalities. Use with caution. ELViS-FA trial excluded patients with EF <35% and uncontrolled arrhythmia.
Talk to Your Doctor
Before considering SS-31 (Elamipretide), discuss it with your healthcare provider. Ask about potential interactions with your current medications, whether it is appropriate for your health conditions, and what monitoring may be needed.
Sources: [1-10]
Evidence Assessment
Elamipretide (Forzinity) received FDA accelerated approval on September 19, 2025 for Barth syndrome based on the TAZPOWER Phase 2/3 trial and open-label extension data (NDA 215244). However, accelerated approval is contingent on confirmatory trials and was based on a surrogate endpoint (knee extensor muscle strength). The Phase 3 MMPOWER-3 trial (n=218) in primary mitochondrial myopathy failed both co-primary endpoints. Active Phase 3 programs (NuPOWER, ReNEW) are ongoing. Given FDA accelerated approval with confirmatory requirements and mixed Phase 3 results across indications, Tier 2 (Phase III+ with conditional approval) is the conservative assessment.
1Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy (MMPOWER)NCT02367014PMID 29540575
Karaa A et al. - Neurology (2018) - Phase 1/2, randomized, double-blind, placebo-controlled, multiple ascending dose - 36 enrolled
Dose-dependent increase in 6MWT distance. Highest IV dose cohort (0.25 mg/kg/hr x 5 days): +51.2 m improvement vs +3.0 m placebo (adjusted p=0.03). Well tolerated.
Limitations: Small sample size, short duration (5 days IV), dose-escalation design. Positive result not replicated in larger Phase 3.
2Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical TrialNCT03323749PMID 36759381
Karaa A, Bertini E et al. - Neurology (2023) - Phase 3, randomized, double-blind, placebo-controlled - 218 randomized (109 per arm)
Failed both co-primary endpoints: 6MWT change -3.2 m difference vs placebo (p=0.69); PMMSA fatigue -0.07 difference (p=0.37). Well tolerated with no new safety signals.
Limitations: Heterogeneous PMM genotypes, challenging endpoint selection, potential placebo effect in 6MWT.
3A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER)NCT03098797PMID 33082543
Thompson WR et al. - Genetics in Medicine (2021) - Phase 2/3, randomized, double-blind, placebo-controlled crossover + open-label extension - 12 in crossover; 10 in OLE
Crossover: primary endpoints not met (6MWT 398 vs 379 m, p=0.08). OLE 36 weeks: 6MWT +95.9 m (p=0.024), BTHS-SA -2.1 (p=0.031), stroke volume +27%. Supported FDA accelerated approval.
Limitations: Very small sample (n=12 crossover), ultra-rare disease, OLE not placebo-controlled, surrogate endpoints.
4Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWERNCT03098797PMID 38602181
Thompson WR et al. (2024) - Open-label extension - 10 participants
Sustained improvements in muscle strength and functional outcomes through 168 weeks. Well tolerated with no new safety signals.
Limitations: Very small sample, no placebo control, open-label design.
5The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipinPMID 23813215
Birk AV et al. - J Am Soc Nephrol (2013) - Preclinical (biophysical and functional) - N/A (in vitro / animal)
Demonstrated SS-31 selectively binds cardiolipin (KD -1.87 μM), inhibits cytochrome c peroxidase activity, protects cristae structure, and re-energizes ischemic mitochondria. Established the cardiolipin-binding mechanism.
Limitations: Preclinical only.
6Mitochondrial protein interaction landscape of SS-31PMID 32554501
Chavez JD et al. - PNAS (2020) - Preclinical (cross-linking mass spectrometry proteomics) - N/A (murine mitochondria)
Identified 12 cardiolipin-binding mitochondrial proteins that interact with SS-31, including complex III/IV subunits, ADP/ATP translocase, ATP synthase, creatine kinase, and OGDH.
Limitations: Mouse heart mitochondria; human interactome may differ.
7In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trialNCT02245620
Siegel MP et al. - PLoS One (2021) - Phase 2, randomized, double-blind, placebo-controlled - 41 randomized
Single IV infusion improved in vivo skeletal muscle ATPmax (31P-MRS) in older adults. Statistically significant improvement vs placebo.
Limitations: Single dose, acute measurement, older adults only.
8ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-Related Macular DegenerationNCT03891875PMID 39600327
Khanani AM et al. - Ophthalmology Science (2024) - Phase 2, randomized, double-blind, placebo-controlled - 176 randomized (117 elamipretide, 59 placebo)
Primary endpoints (LL BCVA, GA area) not met. EZ complete loss reduced by 43% and partial degradation by 47% vs placebo at 48 weeks (secondary endpoints). -¥10 letter LL BCVA gain: 14.6% vs 2.1% (p=0.04).
Limitations: Primary endpoints not met; clinical significance of EZ preservation secondary finding requires confirmation.
9ELViS-FA: Pilot Study to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Friedreich AtaxiaNCT05168774
Lynch D et al. - ClinicalTrials.gov (results posted) (2024) - Phase 1/2, randomized, open-label, parallel - 16 treated (20 enrolled, 4 screen failures)
Low dose (20-30 mg): median +5.5 letters high contrast visual acuity at 52 weeks. High dose (40-60 mg): median 0 change. 8/16 withdrew. SAEs reported likely disease-related.
Limitations: Very small (n=16), open-label, high dropout rate (50%).
10NuPOWER: Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)NCT05162768
Stealth BioTherapeutics (Ongoing) - Phase 3, randomized - Enrollment ongoing
Ongoing late-stage trial in nuclear-DNA primary mitochondrial disease. No results available yet.
Limitations: Ongoing; no results.