SS-31 (elamipretide) in primary mitochondrial myopathy and bioenergetic disorders: effect on the anchor outcome
In the population defined for primary mitochondrial myopathy and bioenergetic disorders, what is the effect of SS-31 (elamipretide) compared with the comparator used in its contributing trials on the anchor outcome for this indication?
Templated review frame. This review question was generated by crossing an indication with a compound for which contributing trials exist. Its prose frame is templated and is shared with other questions of the same shape. Its included studies, its summary of findings and its certainty rating are computed from the underlying records and are not templated. The Institute publishes these questions because the alternative is to leave a question the document set can answer unanswered, and it labels them because the alternative is to present a templated frame as an authored one.
§1Abstract
§1.1Review question
In the population defined for primary mitochondrial myopathy and bioenergetic disorders, what is the effect of SS-31 (elamipretide) compared with the comparator used in its contributing trials on the anchor outcome for this indication?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Genetically determined impairment of oxidative phosphorylation producing myopathy, exercise intolerance or multisystem disease. |
| Intervention | SS-31 (elamipretide) administered as subcutaneous or intravenous in clinical studies. |
| Comparator | The comparator used in each contributing trial, reported per trial rather than pooled across comparator types. |
| Outcomes | Anchor outcome for this indication: Six-minute walk distance. Additional outcomes: Primary mitochondrial myopathy symptom assessment; Muscle phosphocreatine recovery kinetics. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 22 July 2025 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1,2]
§1.4Conclusion
Moderate certainty evidence from 2 contributing trials bears on the effect of SS-31 (elamipretide) on the anchor outcome for primary mitochondrial myopathy and bioenergetic disorders. The estimate the Institute carries in the monograph is: 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. 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.
The conclusion rests on 2 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
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.
- 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
- 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
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.