Elamipretide

Summary

Elamipretide (SS-31) is a novel mitochondria-targeting tetrapeptide that selectively partitions into the inner mitochondrial membrane via interaction with cardiolipin. It reduces oxidative stress, preserves mitochondrial membrane integrity, and enhances bioenergetics. It is under clinical investigation for conditions involving mitochondrial dysfunction including heart failure with preserved ejection fraction (HFpEF), Barth syndrome, primary mitochondrial myopathies, and renal ischemia-reperfusion injury.

Mechanism of Action

Selectively targets and concentrates in the inner mitochondrial membrane; binds to cardiolipin, stabilizing mitochondrial cristae structure, reducing reactive oxygen species (ROS) production, improving electron transport chain efficiency, and preserving mitochondrial function and ATP synthesis.

Routes of Administration

Goals & Uses

• Reduction of oxidative stressAntioxidant / CytoprotectionModerate
• Mitochondrial dysfunction improvementBioenergeticsModerate
• Barth syndrome treatmentRare Genetic DiseaseModerate
• Heart failure with preserved ejection fraction (HFpEF)CardiovascularModerate
• Renal ischemia-reperfusion protectionNephroprotectionModerate
• Primary mitochondrial myopathyNeuromuscular DiseaseModerate

Contraindications

• Severe hepatic impairmentOrganModerateLiver function concerns
• PregnancyPopulationModeratePotential fetal risk or insufficient safety data
• Known hypersensitivity to elamipretide or excipientsAllergyHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• Hypersensitivity reactionImmunologicRare
• NauseaGastrointestinalUncommonFeeling of sickness or urge to vomit
• FatigueGeneralUncommonLow energy or tiredness

Drug Interactions

• ImmunosuppressantsLowPotential interaction with immune pathways or infection risk
• Anticoagulants (e.g., warfarin, heparin)Low

Population Constraints

• Severe renal impairmentOrgan ImpairmentRelative
• Pediatric patientsAgeRelative
• Pregnant or breastfeeding womenReproductiveRelative

Regulatory Status

• European UnionInvestigationalOrphan designation granted by EMA for Barth syndrome. No marketing authorization granted.
• United StatesInvestigationalFDA Orphan Drug Designation for Barth syndrome and primary mitochondrial myopathies. Not approved for any indication. Multiple Phase 2/3 trials completed or ongoing.
• United KingdomInvestigationalNo approval; investigational status following EMA framework pre-Brexit alignment.

Received FDA Orphan Drug Designation for Barth syndrome and primary mitochondrial myopathies. Not yet FDA-approved for any indication. Previously granted Breakthrough Therapy Designation for Barth syndrome (later withdrawn/not maintained). Developed by Stealth BioTherapeutics (now Mitobridge/Astellas).

Evidence & Sources

No sources recorded yet.