Gene Therapy for Fabry Disease to Advance to Phase 2 Clinical Trials

Biotechnology company Avrobio has completed a $60 million Series B financing to advance multiple gene therapies, including AVR-RD-01, a proposed single-dose lentiviral gene therapy for Fabry disease (FD).

FD is caused by absent or deficient activity of the lysosomal enzyme alpha-galactosidase A (a-Gal A) (encoded by the GLA gene), and causes buildup of globotriaosylceramide in cells, which can result in irreversible organ damage. Avrobio’s proposed treatment, AVR-RD-01, is created by extracting and isolating CD34+ stem cells from patients with FD, then transducing them with lentiviral vector that carries a normal GLA gene. The resulting product is infused back into the patient in an out-patient setting in a single dose.

The company will use the newly raised funds to initiate a phase 2 trial of AVR-RD-01 based on promising initial results of a phase 1 clinical trial in 1 patient with FD; the data, presented at the 59th Annual Meeting of the Japanese Society for Inherited Metabolic Diseases, showed that the patient had plasma a-Gal A activity near zero at the study’s initiation. Within 45 days of receiving AVR-RD-01, the patient’s plasma a-Gal A activity increased into the normal range for individuals without FD. The 6-month assessment showed that the patient’s plasma levels remained in the normal range. No related serious adverse events (AEs) were reported during the initial 6-month study period.

If eventually approved, AVR-RD-01 could revolutionize the treatment of FD; currently, the standard of care for the disease is enzyme replacement therapy that involves lifelong, biweekly infusions of the high-cost drug Fabrazyme (agalsidase beta), which carries a price tag of over $300,000 per patient per year. In addition to its expense, Fabrazyme was also subject to a global shortage in 2009 after a manufacturing process introduced viral contamination into the drug supply, and some patients were forced to undergo reduced-dose therapies that resulted in increased rates of serious AEs.

In addition to AVR-RD-01, Avrobio hopes to develop 3 more gene therapies targeting other lysosomal storage disorders: Gaucher disease, and cystinosis (for both of which Avrobio hopes to initiate clinical development by mid-2019), as well as Pompe disease.