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AVROBIO provided an update on its regulatory plans for AVR-RD-01, the first investigational lentiviral gene therapy for Fabry disease. This update follows a recent U.S. regulatory development for Fabry disease therapies, as well as AVROBIO's receipt of minutes from the company's Type B meeting with the U.S. Food and Drug Administration on March 31, On March 11, 2021, approximately three weeks before the company's End-of-Phase 1 meeting, FDA granted full approval of Fabrazyme(R) more than 18 years after the enzyme replacement therapy received accelerated approval on the basis of a surrogate endpoint: reduction of GL-3 (also referred to as Gb3) inclusions in biopsied renal peritubular capillaries. The conversion of Fabrazyme to full approval opens a new pathway for full approval of ERTs based on this surrogate endpoint, which AVROBIO believes could potentially apply to investigational AVR-RD-01. In addition, the conversion of Fabrazyme to full approval limits the accelerated approval pathways available for new therapies to treat Fabry disease. As a result, AVROBIO can no longer pursue an accelerated approval pathway for AVR-RD-01 with the FAB-GT trial as currently designed, and instead intends to discuss with FDA a registration trial with a primary efficacy endpoint of clearance of GL-3/Gb3 inclusions in biopsied renal PTCs as the basis for full approval. "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." In its FDA briefing book, which was submitted to FDA prior to Fabrazyme's full approval, the company sought an accelerated approval pathway by expanding the FAB-GT Phase 2 clinical trial and conducting an additional confirmatory trial. The revised regulatory plan anticipates retaining the two-study approach with a similar overall requirement in terms of scope, size and duration. The company plans to engage FDA to discuss and agree upon its revised approach, with the goal of initiating the registration trial in mid-2022. Although FDA guidance provides that a surrogate endpoint in a particular clinical development program should not be assumed to be appropriate for use in a different program, AVROBIO believes this recent development could potentially apply to investigational AVR-RD-01, a gene therapy designed to facilitate the production of functional enzyme by the patient's own stem cells after a one-time treatment with the therapeutic gene.