Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · §3

SS-31 (elamipretide) — clinical evidence

Assessed outcomes with certainty ratings, contributing trials and the reasoning for each rating.

Document identifier
CEI-MN-044/3
Series
Compound monograph
Version
4.2
Published
17 May 2024
Last reviewed
17 Apr 2025
Next review
17 Apr 2027
Identifier
10.71829/cei.mono.44
Certainty
Moderate
Cycle
2024 Q2

§3Clinical evidence

Assessed outcomes for SS-31 (elamipretide)Point estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.00.20.40.60.81.0Standardised direction and relative magnitude of the recorded effectIndicationEffect as recordedCardiovascular1 trial · ModerateA phase 2 trial in ST-elevation…Mitochondrial disease2 trials · ModerateA phase 3 trial in primary…HFpEF1 trial · LowA phase 2 trial in heart failure with…
Moderate or high certaintyLow or very low certainty
Figure 3. Illustrative. Assessed outcomes plotted on a common standardised axis so that direction and relative magnitude can be compared at a glance. The estimates are not on a common natural scale and the intervals are the Institute's standardised representation of the reported precision, not the published confidence intervals. Published intervals appear in the per-indication extracts and in the text below.

§3.1Atherosclerotic cardiovascular disease and cardiovascular risk reduction

Anchor outcome. Three-point major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke).

Effect as recorded. A phase 2 trial in ST-elevation myocardial infarction did not reduce infarct size; negative result.[1,2]

Certainty. Moderate certainty A clear null result on an objective imaging endpoint.

Contributing trials. EMBRACE-STEMI. Full structured abstracts are published for each.

Full evidence extract for atherosclerotic cardiovascular disease and cardiovascular risk reduction · Indication assessment

§3.2Primary mitochondrial myopathy and bioenergetic disorders

Anchor outcome. Six-minute walk distance.

Effect as recorded. A phase 3 trial in primary mitochondrial myopathy did not meet its primary endpoints of six-minute walk distance and symptom score at 24 weeks; negative result on both primary endpoints.[2,3]

Certainty. Moderate certainty The Institute rates the negative finding moderate certainty. A well-conducted phase 3 trial with a clear null result is stronger evidence about this compound than the entire preclinical literature, and is reported first for that reason.

Contributing trials. MMPOWER-3 · MMPOWER-2. Full structured abstracts are published for each.

Full evidence extract for primary mitochondrial myopathy and bioenergetic disorders · Indication assessment

§3.3Heart failure with preserved ejection fraction and obesity

Anchor outcome. Change in Kansas City Cardiomyopathy Questionnaire clinical summary score.

Effect as recorded. A phase 2 trial in heart failure with preserved ejection fraction did not demonstrate benefit on the primary endpoint; negative result.[3,4]

Certainty. Low certainty Small sample.

Contributing trials. ELAM-PH2-HFPEF. Full structured abstracts are published for each.

Full evidence extract for heart failure with preserved ejection fraction and obesity · Indication assessment

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology 2014;171(8):2029–2050. doi:10.1111/bph.12461 · PMID 24117165
  2. D’Hondt M, Bracke N, Taevernier L, Gevaert B, Verbeke F, Wynendaele E, De Spiegeleer B. Related impurities in peptide medicines. Journal of Pharmaceutical and Biomedical Analysis 2014;101:2–30. doi:10.1016/j.jpba.2014.06.012 · PMID 25044089
  3. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, Devereaux PJ, Montori VM, Freyschuss B, Vist G, Jaeschke R, Williams JW, Murad MH, Sinclair D, Falck-Ytter Y, Meerpohl J, Whittington C, Thorlund K, Andrews J, Schünemann HJ. GRADE guidelines: 6. Rating the quality of evidence — imprecision. Journal of Clinical Epidemiology 2011;64(12):1283–1293. doi:10.1016/j.jclinepi.2011.01.012 · PMID 21839614
  4. Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng HY, Corbett MS, Eldridge SM, Emberson JR, Hernán MA, Hopewell S, Hróbjartsson A, Junqueira DR, Jüni P, Kirkham JJ, Lasserson T, Li T, McAleenan A. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ 2019;366:l4898. doi:10.1136/bmj.l4898 · PMID 31462531

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