We are pleased to share that the prestigious peer-reviewed publication Neurology recently published Phase 1/2 safety and efficacy data from the MMPOWER trial, which studied elamipretide versus placebo in adults with primary mitochondrial myopathy (PMM).1
The data, which were previously presented at the United Mitochondrial Disease Foundation (UMDF) Mitochondrial Medicine 2016, showed that patients treated with elamipretide at the highest dose demonstrated a significant improvement in the six-minute walk test, suggesting that elamipretide may have improved energy production in the body in patients with PMM. No serious adverse events were reported. Elamipretide, Stealth’s lead candidate, is an investigational drug that may restore normal energy production in the body in patients with PMM.
Mitochondria are the body’s main source of energy production and are critical for normal organ function.2 Mitochondrial dysfunction characterizes numerous rare genetic diseases, such as a group of disorders collectively known as primary mitochondrial diseases (PMD), which arise from over 250 different genetic mutations.3 Primary mitochondrial diseases can cause symptoms throughout the body. Primary mitochondrial myopathy is a PMD in which patients primarily experience debilitating muscle weakness and fatigue that hinder their ability to perform everyday tasks.2
In addition to the peer-reviewed publication of MMPOWER in Neurology, Professor John Vissing, Professor of Neurology and Director of the Neuromuscular Clinic and Research unit at the University of Copenhagen, Denmark, and Dr. Corrado Angelini, Professor of Neurology and Director of the Department of Neurosciences Neuromuscular Center at the University of Padova, Italy, published an accompanying editorial titled “Remodel mitochondria and get energized.” In this editorial, it is explained that exercise intolerance in PMM is usually severe and “work capacity is often limited to a third of that in healthy persons, which prevents patients from participating in sport activities and performing activities of daily living such as climbing stairs, grocery shopping, jogging, and playing with children.” Professor Vissing and Dr. Angelini state that the MMPOWER results “are promising and were even coupled with a good safety profile, with no increase in adverse events or laboratory abnormalities compared to placebo.” 4
Individuals with PMM are most often treated with palliative care, which can help ease symptoms but does not address the underlying cause of the disease.5 Currently, there are no U.S. Food and Drug Administration (FDA) approved treatments for PMM or any other rare PMDs.
“We are diligently working toward developing the first generation of targeted therapies focused on mitochondrial dysfunction in rare genetic diseases and common diseases of aging,” said Reenie McCarthy, Stealth Chief Executive Officer. “Central to this goal is the MMPOWER program.”
Following the MMPOWER trial, Stealth initiated MMPOWER-2 to further study the safety and efficacy of elamipretide in patients with PMM. Data from the MMPOWER-2 trial, presented at UMDF’s Mitochondrial Medicine 2017, showed that individuals receiving elamipretide over a four-week period walked an average of 20 additional meters during the six-minute walk test versus those who received placebo. Patients treated with elamipretide also experienced less fatigue, as measured by the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA) and the Neuro-QoL Fatigue Short Form. No serious adverse events were reported. In October 2017, it was announced that the FDA Office of Orphan Products Development granted Orphan Drug Designation to elamipretide for the treatment of patients with PMM.
Results from the MMPOWER-2 trial helped identify the most suitable endpoints to measure changes in skeletal muscle function, fatigue and quality-of-life issues in patients with PMM. These were instrumental in the initiation of MMPOWER-3, a Phase 3 trial designed to evaluate the efficacy and safety of daily injections of elamipretide in individuals with PMM. Eligibility for MMPOWER-3 required patient participation in the observational RePOWER study, which evaluated patients with genetically confirmed or suspected PMM to determine whether there was a relationship between the results of genetic testing and the symptoms patients experienced. Results from MMPOWER-3 are expected in 2019.
- Karaa A, et.al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. Available at: http://n.neurology.org/content/early/2018/03/02/WNL.0000000000005255. Accessed March 2018.
- Cleveland Clinic. Mitochondrial Diseases. Available at: https://my.clevelandclinic.org/health/diseases/15612-mitochondrial-diseases. Accessed February 2018.
- Niyazov DM, et.al. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment. Molecular Syndromology. 2016; 7(3): 122–137.
- Vissing J, et.al. Remodel mitochondria and get energized. Neurology. Available at: http://n.neurology.org/content/early/2018/03/02/WNL.0000000000005243. Accessed March 2018.
- National Cancer Institute. Palliative Care in Cancer. Available at: https://www.cancer.gov/about-cancer/advanced-cancer/care-choices/palliative-care-fact-sheet. Accessed February 2018.