AVROBIO has cancelled its Fabry disease (FD) gene therapy AVR-RD-01, which was due to launch in H2 2022 following disappointing results from a recent Phase II clinical trial. In earlier clinical trials the company had reported promising results for AVR-RD-01 with these recent poor results occurring unexpectedly. This will prove to be significantly disappointing to physicians and patients hoping for a gene therapy with curative potential to enter the FD market. In addition, AVROBIO’s position in the rare disease gene therapy market is likely to be significantly negatively affected as much of its pipeline is based on its lentiviral vector platform that developed AVR-RD-01.

Akash Patel, Pharma Analyst at GlobalData, comments: “Key opinion leaders (KOLs) interviewed by GlobalData have expressed positive sentiment for a gene therapy that has curative potential, especially for severe FD patients, where the current regimen of enzyme replacement therapy (ERT) has proven insufficient. With AVROBIO cancelling its FD program, this will likely provide an increased market share for its competitors in the FD gene therapy space, including 4D Molecular Therapeutics’ 4D-310 and Freeline Therapeutics’ FLT-190, both in Phase II.”

New data demonstrated that five patients in the Phase II trial for AVR-RD-01 may have become resistant to engraftment. AVR-RD-01 was developed to be administered intravenously and consists of autologous CD34+ hematopoietic stem cells genetically modified with lentivirus to express α-Gal A. AVROBIO had initially hoped that the therapy would lead to patients expressing functional copies of the α-Gal A gene that encode for the α-Gal A protein. Previously, AVROBIO had found durable engraftment from 13 patients across three clinical trials for AVR-RD-01, leading to the therapy being indicated as having curative potential for FD patients.

Patel continues: “The FD market will likely have a successful gene therapy entering the market before 2030, but the level of efficacy for such a therapy remains to be determined. In addition, AVROBIO will require good clinical data from its other candidates in the pipeline to remain a leader in the lysosomal storage disease and wider gene therapy market.”