Astellas Pharma Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the development of ASP0367/MA-0211 ("ASP0367") as a potential treatment for primary mitochondrial myopathies (PMM).

PMM is a complex mitochondrial disease in which genetic mutations primarily impair the function of mitochondria, resulting in reduced muscle function, reduced endurance to exercise (i.e., exercise intolerance), increased fatigue, and muscle atrophy. In addition, PMM may present serious and life-threatening health conditions due to multiple organ involvement.  For example, decreased myocardial function may lead to cardiomyopathy and heart failure. Decreased function of respiratory muscles may cause respiratory failure and pneumonia. In patients with mitochondrial disease due to pathogenic mutations in either the mtDNA or nDNA genome, the minimum point prevalence is estimated at 12.5 in 100,000 (approximately 1 in 8,000) for adults with clinical manifestations, and 23 in 100,000 (approximately 1 in 4,300) for adults with or without clinical manifestations. There is no FDA-approved treatment for PMM, a rare disease with a high unmet medical need.

Preclinical data and results from Astellas' Phase I healthy volunteer study collectively suggest that ASP0367 - an orally administered PPARδ modulator - could improve exercise intolerance and fatigue in PMM patients by increasing the number and enhancing the function of mitochondria in patient's cells. ASP0367 will be entering a Phase II / III study (MOUNTAINSIDE) to validate the efficacy and safety of PMM patients.

Astellas explores mitochondrial biology as a Primary Focus of its R&D strategy and is committed to providing treatments using new modalities. Targeting mitochondrial function is an innovative approach to address diseases with significant unmet medical needs in novel and effective ways. With the acquisition of Mitobridge, Inc. in 2018, Astellas has gained access to Mitobridge's expertise in mitochondrial biology and a pipeline of innovative programs including ASP0367.

The FDA's Fast Track designation system aims to expedite the development and review of therapeutic agents for serious or potentially life-threatening diseases with a high unmet medical need. The Fast Track designation is expected to accelerate the clinical development of ASP0367.

"Primary mitochondrial myopathies are a serious, complex disease with significant unmet need and no approved therapies," said Salim Mujais, M.D., Senior Vice President and Therapeutic Area Head, Medical Specialties, Astellas. "With the development of ASP0367, an oral, once-daily modulator of mitochondrial energy production, we are hoping to alleviate the serious burden of this disease on patients, their families and caregivers."

"At Astellas, mitochondrial biology is one of our Primary Focus Areas, driving our commitment to bring new biological concepts into the clinic for rapid proof of concept," said Mike Patane, Ph.D., President of Mitobridge, an Astellas Company, located in Cambridge, Mass. and part of the Astellas Biomedical Innovation Hub. "We are pleased to see this new milestone for ASP0367 as it shows steady progress in our Primary Focus and further demonstrates our focus on turning innovative science into value for patients."

ASP0367, a selective modulator of PPARδ, has the potential to be a first-in-class treatment for PMM. In a preclinical study, ASP0367 increased the expression of PPARδ target genes and enhanced mitochondrial function in fibroblasts collected from patients with PMMs. A phase I study in healthy adults demonstrated dose-dependent increased expression of PPARδ target genes and ASP0367 doses were found to be safe and well-tolerated in this study. ASP0367 is also being developed as a potential treatment for Duchenne muscular dystrophy.