Common and Less Common Side Effects
Based on data from clinical trials for conditions like Barth syndrome, primary mitochondrial myopathy (PMM), and dry age-related macular degeneration (dry AMD), Elamipretide has a generally favorable tolerability profile. The most frequently reported adverse events are mild to moderate in severity and typically transient.
Commonly reported adverse events (incidence >10% in some trials) include:
- Injection site reactions (pain, redness, itching, swelling, induration, bruising)
- Headache
- Dizziness
Less common adverse events reported across trials (incidence <10%) include:
- Nausea
- Abdominal pain
- Fatigue
- Urticaria (hives)
- Flatulence
Serious Side Effects and Allergic Reactions
While most adverse events are mild, serious reactions have been reported. Patients should be aware of the signs of a serious allergic reaction (hypersensitivity), such as rash, hives, severe itching, wheezing, or swelling of the face, lips, tongue, or throat. Immediate medical attention is necessary for serious hypersensitivity reactions, and Elamipretide should be discontinued.
Elamipretide contains benzyl alcohol and is not approved for neonates due to the risk of serious adverse reactions, including potentially fatal outcomes like metabolic acidosis and gasping syndrome, particularly in low-birth-weight and preterm infants.
Serious adverse events (SAEs) in clinical trials were generally rare and often not linked to the drug. No deaths were reported in trials for PMM and Barth syndrome.
Side Effects in Specific Clinical Trials
Barth Syndrome (Forzinity)
In studies for Barth syndrome, daily subcutaneous injections of Elamipretide (Forzinity) most commonly resulted in injection site reactions (erythema, pain, induration, pruritus, bruising, urticaria), occurring more frequently than with placebo. Serious hypersensitivity has also been reported.
Primary Mitochondrial Myopathy (PMM)
MMPOWER-2 and MMPOWER-3 trials for PMM also identified injection site reactions as the most common side effect. In the MMPOWER-2 study, 80% of the elamipretide group experienced injection site reactions, predominantly mild, though one participant stopped treatment due to moderate pain. Dizziness was another less common effect.
Dry Age-Related Macular Degeneration (Dry AMD)
The Phase 2 ReCLAIM-2 trial for dry AMD showed injection site reactions were the most common adverse event in both elamipretide (60%) and placebo (27%) groups, more frequent with the active drug. Common reactions included pruritus, pain, bruising, and erythema, mostly mild to moderate. Discontinuation due to injection site reactions was notable in the elamipretide group (17.1%).
Comparative Overview of Side Effects
The table below compares the incidence of common adverse events in clinical trials of Elamipretide versus placebo, using data from the MMPOWER-2 and ReCLAIM-2 studies.
| Adverse Event | MMPOWER-2 Elamipretide (n=30) | MMPOWER-2 Placebo (n=30) | ReCLAIM-2 Elamipretide (n=117) | ReCLAIM-2 Placebo (n=59) |
|---|---|---|---|---|
| Any Adverse Event | 90% | 70% | 86% | 71% |
| Injection Site Reactions (Any) | 80% | 23.3% | 60% | 27% |
| Injection Site Erythema | 57% | <10% | >5% | N/A |
| Injection Site Pruritus | 47% | <10% | >5% | N/A |
| Headache | <10% | 22.2%* (higher dose) | N/A | N/A |
| Dizziness | 10% | <10% | N/A | N/A |
*Note: Headache incidence for MMPOWER-2 was low; value from MMPOWER Phase I/II.
Conclusion
Clinical data indicates Elamipretide is generally well-tolerated across various mitochondrial-related conditions, primarily with mild-to-moderate injection site reactions as the main side effect. Less common effects include headache, dizziness, and mild GI issues. Serious allergic reactions are rare but require immediate medical care. There is a specific warning regarding benzyl alcohol toxicity in neonates, for whom the drug is not approved. Patients should consult their healthcare provider to discuss potential risks and benefits.
Medical Disclaimer
Disclaimer: This article is for informational purposes only and does not constitute medical advice. It is essential to consult a healthcare professional for diagnosis, treatment, and guidance regarding Elamipretide or any other medication. For prescribing information, please refer to the FDA-approved labeling for Forzinity.
Key Takeaways
Common Adverse Events: The most frequently reported side effects are localized injection site reactions, including pain, redness, swelling, and itching. Injection Site Reaction Management: These reactions are usually mild to moderate and can often be managed with topical corticosteroids or oral antihistamines. Less Common Systemic Effects: Some patients may experience mild systemic effects like headaches, dizziness, abdominal discomfort, or nausea. Risk of Allergic Reaction: Though rare, serious hypersensitivity reactions are possible, requiring immediate medical intervention. Neonatal Warning: The presence of benzyl alcohol means Elamipretide is contraindicated for use in neonates due to the risk of severe toxicity. Overall Tolerability: Overall, Elamipretide has a favorable tolerability profile, and most side effects are mild, transient, and subside over time.
