Recommended Dosing Regimen for Elamipretide (SS31)

Based on the most recent clinical trials, the recommended dosing for Elamipretide (SS31) is 40 mg per day administered subcutaneously.

Evidence-Based Dosing Recommendations

The most recent Phase 3 trial (MMPOWER-3) used a dose of 40 mg/day administered subcutaneously for 24 weeks in patients with primary mitochondrial myopathy 1
Previous Phase 2 trials (MMPOWER-2) also utilized 40 mg/day subcutaneous dosing for 4 weeks 2
Earlier Phase 1/2 trials (MMPOWER) tested intravenous administration at doses of 0.01,0.1, and 0.25 mg/kg/hour for 2 hours, with the highest dose showing the greatest efficacy 3
In patients with Barth syndrome, 40 mg/day subcutaneous dosing was used for up to 36 weeks 4

Subcutaneous administration is the most common and well-studied route in recent clinical trials 1, 2, 4
Intravenous administration has also been studied at 0.05 mg/kg per hour in patients with atherosclerotic renal artery stenosis 5

Injection site reactions are the most commonly reported adverse events (80% in MMPOWER-2), though most are mild in severity 2
The drug is generally well-tolerated with most adverse events being mild to moderate 1

Clinical trials have evaluated treatment durations ranging from 5 days 3 to 24 weeks 1 and up to 36 weeks 4
Longer treatment duration (36 weeks) has shown significant improvements in functional outcomes in Barth syndrome patients 4

Improvement in exercise capacity as measured by the 6-minute walk test (6MWT) is a key efficacy endpoint 1, 2, 3
Patient-reported outcomes measuring fatigue should be monitored, including the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) and Neuro-QoL Fatigue Short Form 1, 2
In the MMPOWER-2 trial, statistically significant improvements were observed in patient-reported fatigue measures after 4 weeks of treatment 2

No specific dosing recommendations for renal impairment were provided in the available evidence
Caution should be exercised in patients with kidney disease, similar to other medications that may affect renal function 5

Elamipretide should be administered as a daily subcutaneous injection of 40 mg 1, 2, 4
Treatment response should be assessed after 4-12 weeks based on functional measures and patient-reported outcomes 2, 4
Long-term treatment (24-36 weeks) may be necessary to observe significant clinical benefits in some conditions 1, 4

The MMPOWER-3 Phase 3 trial did not meet its primary endpoints for the 6MWT and PMMSA total fatigue score despite using the 40 mg/day dose 1
Earlier, smaller trials showed more promising results with the same dosing regimen 2, 3
The optimal duration of treatment may vary based on the specific mitochondrial disorder being treated 1, 4