Table 1. Summary of the main preclinical studies investigating the properties of Elamipretide.
Model Design Results Interpretation Cardiovascular Disease Preclinical studies in animal models of heart failure. Chronic therapy improved LV function, reduced LVESV, increased EF, stroke volume, and cardiac output, while reversing mitochondrial dysfunction, hypertrophy, and fibrosis. Skeletal muscle mitochondrial function and morphology were also restored. The intervention stabilizes cardiolipin, improves energy production, and prevents pathological remodeling, suggesting potential for treating heart failure and post-MI cardiac dysfunction. Renal Disease Murine models of ischemia–reperfusion injury and diabetic nephropathy. The intervention reduced oxidative stress, restored ATP levels, and protected mitochondrial structure, leading to decreased kidney injury and fibrosis. The results highlight the ability to mitigate acute and chronic kidney injury by improving mitochondrial function, offering therapeutic potential for renal diseases. Neurodegenerative Disease Murine models of Alzheimer’s and Parkinson’s diseases. Treatment protected against amyloid-beta toxicity in Alzheimer’s models and preserved dopaminergic neurons in Parkinson’s models, improving mitochondrial function and reducing oxidative stress. The intervention indicates neuroprotective potential by mitigating mitochondrial damage, offering promise for slowing neurodegeneration in Alzheimer’s and Parkinson’s diseases.
Table 2. Main clinical trials testing Elamipretide.
Name Design Results Interpretation Ref(s). EMBRACE-STEMI Multicenter, randomized, double-blind Phase 2a study in first-time anterior STEMI patients undergoing PCI for proximal or mid-LAD artery occlusion.
Dose: 0.05 mg/kg/h for 1 h. No reduction in myocardial infarct size; however, a reduced incidence of chronic heart failure was observed within 24 h post-PCI. While Elamipretide did not impact infarct size, its potential to reduce chronic heart failure warranted further investigation into its cardioprotective effects. [49] PROGRESS-HF Randomized, double-blind, placebo-controlled Phase 2 trial assessing left ventricular function in patients with stable HFrEF.
Dose: 4 or 40 mg. The primary endpoint (LVESV reduction) was not met; mitochondrial function and quality of life showed improvements, though secondary cardiac parameters were unchanged. Longer therapy duration or evaluation during exercise may better capture the benefits of Elamipretide, particularly for cardiac remodeling and mitochondrial dynamics. [50] TAZPOWER Randomized, double-blind, placebo-controlled crossover study in Barth syndrome, followed by a 168-week open-label extension.
Dose: 40 mg. Significant improvements in skeletal muscle strength, cardiac stroke volume, fatigue scores, and cardiac parameters (SV, LVEDV, LVESV) were observed. Sustained efficacy and tolerability highlight the potential of Elamipretide as a therapy for Barth syndrome, with further research needed in younger patients. [51] ReCLAIM (1 and 2) Randomized, double-blind, placebo-controlled Phase 2 trial in patients with dry AMD.
Dose: 40 mg. Primary endpoints (visual acuity and geographic atrophy area) were not met, but progressive EZ degradation, a predictor of vision loss, was slowed. Elamipretide may preserve photoreceptor function by protecting mitochondria, potentially slowing AMD progression. [52,53,54] MMPOWER-3 Randomized, double-blind, placebo-controlled Phase 3 trial in patients with genetically confirmed PMM.
Dose: 40 mg. Primary endpoints, including 6MWT, were not met; however, reduced fatigue was reported, particularly in participants with DNA defects. Subgroup benefits in DNA-related PMM highlight the need for targeted trials to confirm the efficacy of Elamipretide in specific genetic variants. Further investigations are needed to explain why some endpoints were not met. [55]
