Human study PLS-00100

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

Randomized controlled trial · 218 participants enrolled

Version 1 · published November 7, 2026 · evidence through November 7, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

Only the abstract was available. Essential methods may be missing, which limits what can be judged.

Reports of this study

Every publication, registration and abstract describing this one study. Participants are counted once.

Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial.primary · Orphanet journal of rare diseases · 2024-11-21 · PMID 39574155 · DOI
A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extensionregistry entry · NCT03323749 (TERMINATED, results posted, planned enrollment 218)

Design and participants

Design: Randomized controlled trial
Population: Adults with genetically confirmed primary mitochondrial myopathy in MMPOWER-3. 74% had mtDNA pathogenic variants or single large-scale mtDNA deletions. The rest had nDNA variants, mostly in mtDNA replisome genes such as POLG and TWNK. Analyzed post hoc by genotype subgroup.
Conditions: Primary mitochondrial myopathy, mtDNA replisome (maintenance) disorders, Chronic progressive external ophthalmoplegia
Setting: Multicentre Phase 3 clinical trial (registry status terminated); sites not stated in record
Planned enrollment (registry): Not reported
Enrolled: 218
Randomized: Not reported
Completed follow-up: Not reported
Funding: Publication types list NIH extramural and non-US government research support; sponsor not stated.
Authors’ conflicts: Not stated in record

Intervention and comparator

What each group received. Related peptides, analogs and combinations are never treated as the compound itself.

Elamipretide (intervention) · elamipretide · Elamipretide (MTP-131) · Not reported assigned
Placebo (comparator) · Placebo comparator · placebo · Not reported assigned

What the authors reported

As stated in the sources. This is the authors’ account, not Peptide Library’s assessment.

Six-minute walk test distance, overall trial population

primary outcome · patient-important · Six-minute walk test

Elamipretide vs Placebo: narrative — MMPOWER-3 did not show a significant benefit of elamipretide in the genotypically diverse population

Six-minute walk test distance, prespecified nDNA and mtDNA subgroups

secondary outcome · patient-important · Six-minute walk test

Elamipretide vs Placebo: narrative — nDNA subgroup on elamipretide improved on 6MWT; mtDNA cohort showed no difference versus placebo

Six-minute walk test change, mtDNA replisome post hoc cohort

post hoc outcome · patient-important · Six-minute walk test distance change (m)

Elamipretide: change from baseline 25.2 — 25.2 ± 8.7 m improvement in elamipretide group
Placebo: change from baseline 2 — 2.0 ± 8.6 m in placebo group
Elamipretide vs Placebo: narrative, p = 0.06 — Improvement trending towards significance versus placebo

Six-minute walk test change, replisome subjects with CPEO

post hoc outcome · patient-important · Week 24 · Six-minute walk test distance change (m)

Elamipretide: change from baseline 37.3 — 37.3 ± 9.5 m in elamipretide group
Placebo: change from baseline -8 — -8.0 ± 10.7 m in placebo group
Elamipretide vs Placebo: narrative, p = 0.0024 — Significant difference versus placebo at week 24

Exposure-response: plasma elamipretide concentration vs 6MWT improvement, nDNA cohort

post hoc outcome · surrogate · Pharmacokinetic exposure-response correlation

Elamipretide: narrative — Weak positive correlation between plasma concentration and 6MWT improvement

Adverse events

None reported. That is not evidence of safety.

Monitoring: Registry title states safety evaluation; no safety results are given in the record.

The authors concluded (paraphrased): Post hoc analyses suggested elamipretide benefited PMM patients with mtDNA replisome disorders. This supports genotype-specific trial design and a follow-up Phase 3 trial (NuPOWER) in mtDNA maintenance disorders.

Peptide Library’s assessment

An automated assessment, made by AI separately from the authors’ conclusions and not reviewed by a person. How risk of bias is assessed.

Limitations

selective reporting: Subgroups such as the replisome and CPEO cohorts were defined post hoc after the main trial failed its primary endpoint, so the risk of chance findings is high.
small or imprecise: Subgroup sizes are not stated and the replisome result was not significant (p = 0.06); the estimates are imprecise.
abstract only: Only the abstract and registry fields are available; arm sizes, dosing, attrition and safety data are not reported.
other: The overall trial showed no significant benefit, so the positive findings come from genotype-restricted subsets only.
funding or conflicts: Funding is only partly described and conflicts of interest are not stated in the record.

Six-minute walk test distance, overall trial population: Some concerns (Cochrane RoB 2)