EMA accepts regulatory submission for avalglucosidase alfa, an enzyme replacement therapy for Pompe disease.- Genzyme/Sanofi

The European Medicines Agency (EMA) has accepted for review the Marketing Authorization Application (MAA) from Genzyme/ Sanofi for avalglucosidase alfa, for long-term enzyme replacement therapy for the treatment of patients with Pompe disease (acid alfa-glucosidase deficiency). Avalglucosidase alfa is an investigational enzyme replacement therapy, which, if approved, would offer a potential new standard of care for patients with Pompe disease. Pompe disease is a rare, degenerative muscle disorder that can impact an individual’s ability to move and breathe. It affects an estimated 50,000 people worldwide and can manifest at any age from infancy to late adulthood. Regulatory approval in Europe anticipated in the second half of 2021. The MAA is based on positive data from two trials : Phase III, double-blind, comparator-controlled, pivotal COMET trial , which evaluated the safety and efficacy of avalglucosidase alfa compared to alglucosidase alfa (standard of care) in patients with late-onset Pompe disease. Results from this trial were presented during a Sanofi-hosted virtual scientific session in June 2020. Phase II mini-COMET trial which evaluated the safety and exploratory efficacy of avalglucosidase alfa in patients with infantile-onset Pompe disease previously treated with alglucosidase alfa. Results from this trial were presented at the WORLDSymposium, in February 2020. The Medicines and Healthcare Products Regulatory Agency in the UK has granted Promising Innovative Medicine designation for avalglucosidase alfa, an early indication that the investigational therapy is a promising candidate for the Early Access to Medicines Scheme in the UK. The FDA has granted Breakthrough Therapy and Fast Track designations to avalglucosidase alfa. . Delivery of GAA to Clear Glycogen: To reduce the glycogen accumulation caused by Pompe disease, the GAA enzyme must be delivered into the lysosomes within muscle cells. Research led by Sanofi has focused on ways to enhance the delivery of GAA into the lysosomes of muscle cells by targeting the mannose-6-phosphate (M6P) receptor that plays a key role in the transport of GAA. Avalglucosidase alfa is designed with approximately 15-fold increase in M6P content, compared to alglucosidase alfa, and aims to help improve cellular enzyme uptake and enhance glycogen clearance in target tissues.The clinical relevance of this difference has not been confirmed.