PeptideTreatments
Reviewed by Peptide Treatments Medical Advisory Board

SS-31: Research & Evidence

Emerging Evidence

Published research, clinical trial data, and evidence grading for SS-31 across studied indications.

Back to SS-31 overview

Research Summary

SS-31/elamipretide has completed 8+ Phase 2 trials with 800-1,000 total subjects exposed and 6+ placebo-controlled RCTs. The EMBRACE-HF trial (n=67) showed a 42-meter improvement in 6-minute walk distance vs 10 meters for placebo in HFpEF patients. It received FDA Breakthrough Therapy designation for HFpEF (2019) and Fast Track designation for primary mitochondrial disease. Two Phase 3 trials (SPRING-HF, n=600 and mitochondrial disease, n=400) are currently recruiting with readouts expected 2026-2027.

Evidence by Indication (4 indications)

Indication Tier Trials Summary
Heart failure Tier B 4 Phase 2 trials show improved cardiac function and exercise capacity in HFpEF and HFrEF; Phase 3 recruiting
Mitochondrial dysfunction Tier C 3 Barth syndrome and primary mitochondrial myopathy trials show functional improvement; mixed primary endpoints
Age-related decline Tier C 1 Improved exercise tolerance in elderly subjects via cardiolipin stabilization mechanism
Duchenne muscular dystrophy Tier C 1 Modest functional improvement in Phase 2; mechanism supports further investigation

Graded using our evidence tier methodology.

Research Gap Score /10

Higher score = larger gap between therapeutic potential and available clinical evidence.

Citations (11 sources)

  1. 1. EMBRACE-HF Phase 2 trial of elamipretide in HFpEF Clinical Trial

    Various (2021), JACC: Heart Failure

  2. 2. Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential Review

    (2025), International journal of molecular sciences

  3. 3. The Mitochondria-Targeted Peptide Therapeutic Elamipretide Improves Cardiac and Skeletal Muscle Function During Aging Without Detectable Changes in Tissue Epigenetic or Transcriptomic Age Study

    (2025), Aging cell

  4. 4. Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial Clinical Trial

    (2024), Orphanet journal of rare diseases

  5. 5. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER Study

    (2024), Genetics in Medicine

  6. 6. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial Clinical Trial

    (2023), Neurology

  7. 7. New insight for SS-31 in treating diabetic cardiomyopathy: Activation of mitoGPX4 and alleviation of mitochondria-dependent ferroptosis Study

    (2024), International journal of molecular medicine

  8. 8. SS-31 alleviated nociceptive responses and restored mitochondrial function in a headache mouse model via Sirt3/Pgc-1alpha positive feedback loop Study

    (2023), The journal of headache and pain

  9. 9. Elamipretide (SS-31) Attenuates Idiopathic Pulmonary Fibrosis by Inhibiting the Nrf2-Dependent NLRP3 Inflammasome in Macrophages Study

    (2023), Antioxidants

  10. 10. The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT). Study

    Pharaoh G, Kamat V, Kannan S, et al. (2023), GeroScience

  11. 11. Application research of novel peptide mitochondrial-targeted antioxidant SS-31 in mitigating mitochondrial dysfunction. Study

    Du X, Zeng Q, Luo Y, et al. (2024), Mitochondrion