“Receiving orphan drug designation from FDA is a positive step forward in our global strategy to advance single-dose, gene therapy as a new treatment paradigm for Fabry disease. We see a promising opportunity for gene therapy to displace today’s enzyme replacement therapies that currently leave significant disease progression, a shortened lifespan and other unmet medical needs for patients with Fabry disease,” Geoff MacKay, president and CEO of Avrobio, said in a press release.
The gene therapy AVR-RD-01 is based on autologous stem cell transplant — when stem cells are removed from a person, stored, and later reinserted into that same person so the cells can perform a therapeutic function. Stem cells allow for the development of an unlimited source of almost any type of human cell needed for therapeutic purposes.
In some cases, after being removed from the patient, the stem cells are modified to correct a non-functional or defunct gene before being reinserted into the patient to replace disease-causing cells with healthy cells. This can be done using lentiviral gene therapy, which offers permanent genomic integration, with a demonstrated safety record, for a durable and long-term curative benefit.
Fabry disease is caused by a defect in the GLA gene, resulting in the deficiency of the enzyme alpha-galactosidase A. This enzyme is essential for the metabolism of a fatty substance called globotriaosylceramide, which accumulates in various cells throughout the body, causing the progressive clinical signs and symptoms associated with Fabry disease.
AVR-RD-01 uses hematopoietic stem cells — stem cells that give rise to other blood and immune cells — to produce functional alpha-galactosidase A enzyme. The hematopoietic stem cells are infected with a harmless virus carrying a functional version of the GLA gene encoding alpha-galactosidase A before being reinserted into the patient.
The ongoing AVR-RD-01 clinical trials are evaluating whether re-introducing hematopoietic stem cells with a corrected GLA gene will safely and effectively help increase the levels of alpha-galactosidase A enzyme.
Because Fabry disease is an X-linked disorder — the GLA gene is positioned on the X-chromosome — males typically are affected more severely than females, who have a more variable course of disease and may be asymptomatic or less severely affected as males. For this reason, these clinical trials are only recruiting adult male participants.
“Working with medical leaders, experts and patient advocates, we are committed to moving forward with the clinical and commercial development of our gene therapies because of the potentially dramatic benefit a single-dose therapy can have in transforming the lives of patients,” MacKay said.
In addition to the work on Fabry disease, Avrobio is working to deliver gene therapy-based therapeutics that restore normal gene function to patients with other rare diseases, including Gaucher disease, Pompe disease, and cystinosis.
The FDA’s orphan drug designation provides special status to drugs and biologics proposed for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the U.S.