Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome.

Hornby B, Thompson WR, Almuqbil M, Manuel R, Abbruscato A, Carr J, Vernon HJ

Orphanet journal of rare diseases2 Sept 2022Cited by 17 (Europe PMC)

PMID36056411PMCIDPMC9438322DOI10.1186/s13023-022-02469-5PepBankPUB-36056411

Summary

BackgroundNatural history studies are increasingly recognized as having an important role in drug development for rare diseases. A phase 3, observational, retrospective, and non-interventional study was designed to establish a natural history control (NHC) cohort of patients with Barth syndrome (BTHS) to provide further analysis of the efficacy of elamipretide observed in an open-label extension (OLE) phase of the TAZPOWER trial, a clinical trial that tested the efficacy of 40 mg daily of elamipretide in patients with BTHS.MethodsThis was a retrospective, non-interventional study. A propensity score model was used to compare elamipretide-treated patients and NHCs. The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).ResultsFor the 6-min walk test (6MWT, primary endpoint), the least squares (LS) mean difference between groups was 79.7 m (P = 0.0004) at week 64 and 91.0 m (P = 0.0005) at week 76 in favor of elamipretide. Significant improvements in muscle strength (secondary endpoint), as assessed by handheld dynamometry (HHD) were also observed with elamipretide, with LS mean differences of 40.8 Newtons at 64 weeks (P = 0.0002) and 56.7 Newtons at 76 weeks (P = 0.0005). Patients continuously treated with elamipretide also experienced statistically significant improvements in other secondary endpoints (i.e., 5 times sit-to-stand [5XSST], multi-domain responder index [MDRI]). The functional improvements were robust to sensitivity analyses. Left ventricular stroke volume increased from baseline in patients with elamipretide but decreased in NHCs.ConclusionsOverall, the study established a NHC for use in assessing the efficacy of therapeutic interventions in patients with BTHS and the results suggest that elamipretide may improve natural history of BTHS at least in part by attenuating the natural decline in heart function and provide meaningful improvements in heart function and functional capacity in patients with BTHS compared to NHCs.HighlightsA matched Natural History Control (NHC) was used to evaluate elamipretide in BTHS Elamipretide may improve natural history of BTHS by attenuating natural decline in heart function Elamipretide was associated with meaningful clinical improvements in skeletal muscle and cardiovascular parameters that were not observed in NHCs The study established a NHC for use in assessing the efficacy of therapeutic interventions in BTHS.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

5 results from studies that gave the peptide. 5 results from people.

01HumanNon-randomized trialEfficacy outcome
In patients with Barth syndrome, elamipretide improved 6-min walk distance versus untreated natural history controls at week 64 and week 76.
In plain wordsIn people with Barth syndrome, those treated with elamipretide walked farther in 6 minutes than untreated patients.
Peptide
Elamipretide (SS-31)
Outcome
Increase6-min walk test distance
Study
n = 27
Comparator
Untreated natural history controls
Analysis
Primary
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
40 mg dailyAs given in this study (human).
Measurements
LS mean difference 6MWT
79.7 m
week 64
LS mean difference 6MWT
91 m
week 76
Source sentences
Summary
For the 6-min walk test (6MWT, primary endpoint), the least squares (LS) mean difference between groups was 79.7 m (P = 0.0004) at week 64 and 91.0 m (P = 0.0005) at week 76 in favor of elamipretide.
2 context sentences(design, population, supporting numbers)
Summary · context
tested the efficacy of 40 mg daily of elamipretide in patients with BTHS
Summary · context
The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).
Show in the study text Report a problemFND-3605641101
02HumanNon-randomized trialEfficacy outcome
In patients with Barth syndrome, elamipretide improved muscle strength by handheld dynamometry versus untreated natural history controls at weeks 64 and 76.
In plain wordsIn people with Barth syndrome, elamipretide-treated patients had greater muscle strength than untreated patients.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMuscle strength by handheld dynamometry
Study
n = 27
Comparator
Untreated natural history controls
Analysis
Secondary
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
40 mg dailyAs given in this study (human).
Measurements
LS mean difference HHD
40.8 Newtons
week 64
LS mean difference HHD
56.7 Newtons
week 76
Source sentences
Summary
Significant improvements in muscle strength (secondary endpoint), as assessed by handheld dynamometry (HHD) were also observed with elamipretide, with LS mean differences of 40.8 Newtons at 64 weeks (P = 0.0002) and 56.7 Newtons at 76 weeks (P = 0.0005).
2 context sentences(design, population, supporting numbers)
Summary · context
tested the efficacy of 40 mg daily of elamipretide in patients with BTHS
Summary · context
The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).
Show in the study text Report a problemFND-3605641102
03HumanNon-randomized trialEfficacy outcome
In patients with Barth syndrome, continuous elamipretide treatment improved the 5 times sit-to-stand test versus untreated natural history controls.
In plain wordsIn people with Barth syndrome, elamipretide improved sit-to-stand performance compared with untreated patients.
Peptide
Elamipretide (SS-31)
Outcome
Increase5 times sit-to-stand test
Study
n = 27
Comparator
Untreated natural history controls
Analysis
Secondary
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
40 mg dailyAs given in this study (human).
Source sentences
Summary
Patients continuously treated with elamipretide also experienced statistically significant improvements in other secondary endpoints (i.e., 5 times sit-to-stand [5XSST]
2 context sentences(design, population, supporting numbers)
Summary · context
tested the efficacy of 40 mg daily of elamipretide in patients with BTHS
Summary · context
The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).
Show in the study text Report a problemFND-3605641103
04HumanNon-randomized trialEfficacy outcome
In patients with Barth syndrome, continuous elamipretide treatment improved the multi-domain responder index versus untreated natural history controls.
In plain wordsIn people with Barth syndrome, elamipretide improved a combined responder score compared with untreated patients.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseMulti-domain responder index
Study
n = 27
Comparator
Untreated natural history controls
Analysis
Secondary
Outcome group
Exercise and physical function · Musculoskeletal
Studied dose
40 mg dailyAs given in this study (human).
Source sentences
Summary
Patients continuously treated with elamipretide also experienced statistically significant improvements in other secondary endpoints (i.e., 5 times sit-to-stand [5XSST], multi-domain responder index [MDRI]).
2 context sentences(design, population, supporting numbers)
Summary · context
tested the efficacy of 40 mg daily of elamipretide in patients with BTHS
Summary · context
The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).
Show in the study text Report a problemFND-3605641104
05HumanNon-randomized trialEfficacy outcome
In patients with Barth syndrome, left ventricular stroke volume increased from baseline with elamipretide but decreased in untreated natural history controls.
In plain wordsIn people with Barth syndrome, heart stroke volume rose with elamipretide but fell in untreated patients.
Peptide
Elamipretide (SS-31)
Outcome
IncreaseLeft ventricular stroke volume
Study
n: not reported in source
Comparator
Untreated natural history controls
Outcome group
Heart function · Cardiovascular
Studied dose
40 mg dailyAs given in this study (human).
Source sentences
Summary
Left ventricular stroke volume increased from baseline in patients with elamipretide but decreased in NHCs.
2 context sentences(design, population, supporting numbers)
Summary · context
tested the efficacy of 40 mg daily of elamipretide in patients with BTHS
Summary · context
The analysis included 8 patients from the TAZPOWER OLE and 19 untreated NHCs (including 12 with serial echocardiographic assessments).
Show in the study text Report a problemFND-3605641105

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Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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