SS-31 (elamipretide) in primary mitochondrial myopathy and bioenergetic disorders: tolerability and… — summary of findings
Outcome-by-outcome summary with effect, certainty and the reason for each downgrade.
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.
§4Summary of findings
§4.1Summary of findings
Table 7. Summary of findings for SS-31 (elamipretide) in primary mitochondrial myopathy and bioenergetic disorders….
| Outcome | Participants (studies) | Effect as reported | Certainty | Reason for downgrade |
|---|---|---|---|---|
| Six-minute walk distanceThe outcome the Institute designates as anchor for this indication. | 248 (2) | Neither primary endpoint was met. The Institute records MMPOWER-3 as a negative phase 3 result and treats it as informative… | Moderate | inconsistency |
| Discontinuation for adverse eventsReported as a summary-of-findings row rather than in a tolerability annex, following a public submission. | 242 (1) | Reported per contributing trial; see the included-studies table | Moderate | indirectness |
| Serious adverse eventsEvent counts are low; the estimate is imprecise by construction. | 194 (1) | Reported per contributing trial; see the included-studies table | Low | indirectness |
| Any adverse eventAscertained by spontaneous report in the contributing trials. | 230 (2) | Reported per contributing trial; see the included-studies table | Low | inconsistency, publication bias |
| Primary mitochondrial myopathy symptom assessmentA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it. | 118 (1) | Reported as a secondary outcome in a subset of contributing trials | Low | risk of bias, inconsistency |
| Muscle phosphocreatine recovery kineticsA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it. | 121 (1) | Reported as a secondary outcome in a subset of contributing trials | Low | publication bias |
| Certainty ratings describe confidence in the effect estimate for the stated outcome. They are not recommendations and do not transfer between outcomes. | ||||
§4.2Forest plot
§4.3Certainty assessment for the anchor outcome
Table 8. Reasoning recorded against each certainty domain for the anchor outcome.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | No concern | No serious concern identified in this domain. |
| Inconsistency | Serious | Direction is consistent; magnitude varies with the intensity of the background intervention. |
| Indirectness | No concern | No serious concern identified in this domain. |
| Imprecision | No concern | No serious concern identified in this domain. |
| Publication bias | No concern | No serious concern identified in this domain. |
| Overall: Moderate certainty. The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate. | ||
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
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