MPSII Gene Therapy Granted Orphan Drug Designation


AVROBIO decided to deprioritize their Fabry disease gene therapy program in January 2022.

The FDA has granted orphan drug designation to AVROBIO’s gene therapy AVR-RD-05 for the potential treatment of mucopolysaccharidosis type II (MPSII) also known as Hunter syndrome.1

AVR-RD-05 is a hematopoietic stem cell (HSC) gene therapy transduced ex vivo with a lentiviral vector that encodes the human IDS enzyme. AVROBIO is planning to evaluate the therapy in a phase 1/2 clinical trial in 2023 sponsored by AVROBIO’s collaborator, University of Manchester, in the UK. Brian Bigger, PhD, professor of cell and gene therapy at the University of Manchester previously published preclinical data demonstrating that the HSC gene therapy approach had the potential to correct peripheral disease and normalize brain pathology.

AVROBIO is developing multiple gene therapies to treat lysosomal diseases in addition to AVR-RD-05. Among those in clinical trials are AVR-RD-02 for the treatment of Gaucher disease type 1 (NCT04145037) and AVR-RD-04 for the treatment of cystinosis (NCT03897361). AVROBIO was also developing AVR-RD-01 for the treatment of Fabry disease but the company announced in January 2022 that they were deprioritizing the program and stopping recruitment in the phase 1/2 FAB-GT trial (NCT03454893).2 The decision was made after disappointing engraftment data was observed in the 5 most recently treated participants.

READ MORE: Patient-Informed Study to Evaluate Hunter Syndrome Gene Therapy

“Previously reported data from 13 patients treated across our three clinical-stage programs have shown durable engraftment out 9 to 54 months. It is the new data from the 5most recently dosed Phase 2 FAB-GT patients that are discordant with these other data and show variable engraftment. In addition, the last 12 months have presented multiple challenging market and regulatory dynamics for our Fabry disease program, which would now be exacerbated by a meaningfully extended development timeline,” Geoff MacKay, president and chief executive officer, AVROBIO, said in a statement.2

AVROBIO also presented data on the analytical pipeline they have developed for their molecular follow-up of lentiviral cell therapies in patients with lysosomal disease at the 18th Annual WORLDSymposium, February 7-11, 2022 in San Diego, CA.3 The presentation was given by Luca Biasco, PhD, director, research and development, AVROBIO.

“As you would study the pharmacokinetics of chemical drugs, you need to also monitor the biodistribution and dynamics of these cells, with the added complexity that these cells are a much more complicated vehicle for therapies,” Biasco told CGTLive in an interview.

1. AVROBIO receives orphan drug designation from the U.S. Food and Drug Administration for AVR-RD-05, a gene therapy for mucopolysaccharidosis type II (MPSII) or Hunter syndrome. News release. AVROBIO. July 13, 2022.
2. AVROBIO reprioritizes pipeline programs. News release. AVROBIO. January 4, 2022.
3. Biasco L, Baricordi C, Loperfido M, et al. High throughput monitoring of safety, potency and stability of gene therapy cell products in lysosomal disease patients. Presented at: 18th Annual WORLDSymposium. February 7-11, 2022; San Diego, CA. Poster #26
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