Sanofi's Avalglucosidase Alfa Receives FDA Priority Review for Pompe Disease, Poised to Become New Standard of Care

Recently, Sanofi announced that the U.S. FDA has accepted its Biologics License Application (BLA) for avalglucosidase alfa as a long-term enzyme replacement therapy for patients with glycogen storage disease type II (also known as Pompe disease). The FDA also granted priority review status to this application, with an expected response by May 8 next year.

Pompe disease is a rare degenerative muscle disorder that affects an individual’s mobility and respiratory function. In the United States, an estimated 3,500 people are affected by this condition, which can manifest at any age from infancy to adulthood. It is caused by a genetic defect or dysfunction of acid alpha-glucosidase (GAA) in the lysosomes, leading to glycogen accumulation in muscle cells throughout the body. This ultimately results in irreversible muscle damage, including to the respiratory muscles and diaphragm that support pulmonary function, as well as other skeletal muscles that affect mobility.

Avalglucosidase alfa is an investigational enzyme replacement therapy designed to improve the delivery of GAA to muscle cells. To reduce glycogen accumulation, GAA must be delivered to the lysosomes within muscle cells. Research led by Sanofi has primarily focused on enhancing the delivery of GAA to lysosomes in muscle cells by targeting the mannose-6-phosphate (M6P) receptor, which plays a key role in GAA transport. Compared with the standard treatment, alglucosidase alfa, avalglucosidase alfa has approximately 15-fold higher M6P content, aiming to help improve cellular uptake of the enzyme and enhance targeted glycogen clearance. This investigational therapy has been granted Breakthrough Therapy Designation and Fast Track designation by the FDA for the treatment of Pompe disease. If approved, it would provide a potential new standard of care for these patients.

▲Glycogen degradation is impaired in patients with Pompe disease (Image source: pompe.com)

This BLA is based on the results of two clinical trials. One was a pivotal, double-blind, active-controlled Phase 3 clinical trial evaluating the safety and efficacy of avalglucosidase alfa compared with acid alpha-glucosidase (standard of care) in patients with late-onset Pompe disease. The other was a Phase 2 clinical trial assessing the safety and exploratory efficacy of avalglucosidase alfa in infantile-onset patients who had previously received acid alpha-glucosidase therapy. The results of both clinical trials were presented at medical conferences earlier this year.

References:

[1] FDA grants priority review for avalglucosidase alfa, a potential new therapy for Pompe disease. Retrieved November 17, 2020, from https://www.globenewswire.com/news-release/2020/11/18/2128825/0/en/FDA-grants-priority-review-for-avalglucosidase-alfa-a-potential-new-therapy-for-Pompe-disease.html

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