Global Mitochondrial Disease Awareness Week 9/17
SHARE THE WAYS MITOCHONDRIA MATTER THIS WEEK
September 17-23 is Global Mitochondrial Disease Awareness Week. Mitochondria are in every cell of our body, except red blood cells, and are tiny cellular powerhouses, essential for energy creation in organ systems, like brain, heart and muscles. Approximately 1 in 2,500 adults, teens and children are affected, making mitochondrial disease more common than childhood cancers. Mitochondrial dysfunction is proven to be at the root of many common diseases and conditions that affect young and old, from Autism to Parkinson’s, Alzheimer’s, some cancers, and it may even be responsible for aging itself. With mitochondrial dysfunction contributin
g to so many disparate diseases, collaboration across specialties, among clinicians, researchers and pharmaceutical companies is vital. Non-profit organizations, such as ours, are forming partnerships to maximize our work. To learn more about mitochondrial disease, and how you can help progress research and treatment, please visit: www.hopeflies.org www.mitoaction.org www.umdf.org
The Foundation for Mitochondrial Medicine’s mission is to support the development of the most promising research and treatments for the many forms of mitochondrial disease. Treatments for mitochondrial disease could impact cures for Autism, Alzheimer’s, Parkinson’s, muscular dystrophy and more. For more information on FMM-funded research such as functional MRI studies on cognitive fatigue and testing of new drug compounds, visit www.mitochondrialdiseases.org
MitoAction is a nonprofit organization dedicated to improving the quality of life for children, adults, and families living with mitochondrial disease through support, education, outreach, advocacy, and clinical research initiatives. For more information, visit www.mitoaction.org.
Founded in 1996, the United Mitochondrial Disease Foundation (UMDF) works to promote research and education for the diagnosis, treatment and cure of mitochondrial diseases and to provide support for affected individuals and families. Since its inception, the UMDF has funded nearly $11.5 million in research, making it the leading non-governmental contributor of grants focused solely on mitochondrial disease. The UMDF, based in Pittsburgh, PA, is a national organization, represented around the world by thousands of members. For more information about mitochondrial disease or the UMDF, visit www.umdf.org
Stealth BioTherapeutics Shares Promising Data From Mitochondrial Myopathy Trial
July 19, 2017
STEALTH BIOTHERAPEUTICS SHARES PROMISING DATA FROM MITOCHONDRIAL MYOPATHY TRIAL
Recently, at the 2017 UMDF Mitochondrial Medicine Symposium, Stealth BioTherapeutics shared very encouraging results from its second clinical trial for primary mitochondrial myopathy, the MMPOWER-2 study. Stealth is a Boston-based biopharmaceutical company developing therapeutics to treat mitochondrial dysfunction; its lead drug under investigation is elamipretide (previously known as Bendavia). Primary mitochondrial myopathy (PMM) is a genetically-acquired mitochondrial disease characterized by signs and symptoms of myopathy (debilitating muscle weakness, easy fatigability, exercise intolerance and pain). The Phase 2 MMPOWER-2 trial was conducted to evaluate safety, tolerability and efficacy of treatment using elamipretide in 30 adult (ages 16-65) patients with PMM. An overall assessment of the top-line MMPOWER-2 results showed benefit across multiple endpoints and is supportive of continuation toward a Phase 3 study in this patient population.
Patients enrolled in MMPOWER-2 previously participated in Stealth’s MMPOWER trial, designed to assess dosing, which demonstrated a dose-dependent improvement in distance walked in the 6-Minute walk test (6MWT) after 5 days of once daily intravenous administration of elamipretide or placebo. In MMPOWER-2, patients were randomized to once daily subcutaneous administration of elamipretide or placebo for a longer period of time (four weeks), and then, after a washout period, received the opposite treatment during a second four-week dosing period. Patients, their doctors and investigators at Stealth were unaware of which group patients belonged to during the trial and the subsequent assessments.
This type of study design, known as a randomized, double-blind, placebo-controlled crossover study, is considered a “gold standard” in clinical trials evaluating investigational drugs. Randomized controlled trials can be challenging in rare and orphan diseases because there simply are not as many patients available to participate, and there tend to be as many differences as there are similarities between patients who may have the same diagnosis (also known as heterogeneity).
Multiple endpoints, or outcomes, were considered and evaluated during the MMPOWER-2 trial in addition to the 6MWT, including the Neuro-QoL (Quality of Life in Neurological Disorders) measurement system, and a new patient-reported outcome tool, the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA), developed by Stealth specifically for this patient population. Other tools and measures for safety, tolerability and functional assessment were also applied.
Chuck Mohan, Executive Director of the United Mitochondrial Disease Foundation, comments “Clinical trials for rare diseases are challenging and we are very supportive of Stealth for their efforts to evaluate potential therapeutics in a meaningful, rigorous and scientific manner. The progress of the MMPOWER-2 trial provides hope to our global mitochondrial disease community. ”
The primary objective of the study was to evaluate the effect of a single daily subcutaneous dose of elamipretide for four weeks on a PMM patient’s walking distance, as measured by the 6MWT. Patients receiving elamipretide walked an average of 20 meters more than those receiving placebo at the end of the 4-week dosing period. In addition, those patients who were the most impaired at baseline demonstrated the greatest improvement.
Data gathered and analyzed for several other secondary endpoints is also informative and promising. Treatment with elamipretide resulted in statistically significant and clinically meaningful improvements in the Neuro-QOL Fatigue Short Form score and in the PMMSA Total Fatigue score. In other words, patients showed overall improvement in fatigue and in symptoms which impacted their daily quality of life and functional abilities. Patients also reported a statistically significant improvement in the PMMSA identified symptom most bothersome to them individually, such as tiredness, muscle weakness, muscle pain, abdominal discomfort, vision problems, or balance problems. Data also continued to demonstrate safety and tolerability of elamipretide, with the most common side effect being redness or itching at the injection site.
Kira Mann, CEO of MitoAction, is enthusiastic about these findings. “These results are very promising for patients struggling with fatigue, pain, and weakness due to mitochondrial myopathy. On behalf of patients and families with mitochondrial disease, we are excited about this data and continue to be supportive of future elamipretide studies.”
Stealth continues to be committed to developing mitochondrial therapeutics and engaging with the mitochondrial disease clinician and patient/family community. In March of 2017, Stealth initiated RePOWER, a prospective, observational study of patients with mitochondrial myopathy. RePOWER will assess approximately 300 PMM patients, ages 16-65, and will gather information about current symptoms, quality of life, functional abilities and medical history. Findings from MMPOWER, MMPOWER-2 and RePOWER will together help establish and inform a Phase 3 trial to continue to evaluate the potential efficacy, safety and tolerability of elamipretide. Stealth plans to launch its Phase 3 trial around the end of this year.
The executive director of the Foundation for Mitochondrial Medicine, Laura Stanley, has a child with mitochondrial disease. She states, “Results such as these demonstrate why it is so important for every patient and family with primary mitochondrial disease to be involved in these very important and groundbreaking studies. Together we are pioneering this field.”