The FDA has granted full approval for Sanofi’s Fabrazyme, which means Avrobio can no longer pursue an accelerated approval pathway for AVR-RD-01.
AVR-RD-01 is an investigational ex vivo lentiviral gene therapy designed to provide therapeutic benefit for people with Fabry disease. Three weeks before Avrobio’s End-of-Phase I meeting, the FDA granted full approval of Fabrazyme for the treatment of Fabry disease, more than 18 years after the enzyme replacement therapy (ERT) originally received accelerated approval. The approval was granted on the basis of reduction of GL-3 inclusions in biopsied renal peritubular capillaries as a surrogate endpoint.
The approval Fabrazyme opens a new pathway for approval of ERTs based on this surrogate endpoint, which could potentially apply to AVR-RD-01. However, the conversion of Fabrazyme to full approval also limits the accelerated approval pathways available for new therapies for Fabry disease. This means Avrobio can no longer pursue an accelerated approval pathway for AVR-RD-01 with its current trial design.
Avrobio now has plans for a registration trial with a primary efficacy endpoint of clearance of GL-3 inclusions in biopsied renal PTCs as the basis for full approval. The company hopes to discuss and agree upon this revised approach with the FDA, with the aim of initiating the registration trial in mid-2022.
“We believe we have a potential new path to pursue full approval for investigational AVR-RD-01 as a first-line therapy for Fabry disease by conducting a single, head-to-head registration trial versus Fabrazyme using a kidney biopsy surrogate endpoint similar to our FAB-GT Phase 2 trial, where we have seen 100% and 87% substrate reductions at one year post-gene therapy in the two patients with evaluable kidney biopsies,” said Geoff MacKay, CEO and president of Avrobio. “We plan to design a registration trial with a scope, size and duration comparable to other gene therapy trials.”