FDA Grants Orphan Designation to AVR‑RD‑02 Gene Therapy for Gaucher Disease

FDA Grants Orphan Designation to AVR‑RD‑02 Gene Therapy for Gaucher Disease

The U.S. Food and Drug Administration (FDA) granted orphan drug designation to AVR-RD-02, a gene therapy candidate for the treatment of Gaucher disease.

AVR‑RD‑02, being developed by Avrobio, recently advanced to its first clinical study of the therapy’s safety and effectiveness in patients with type 1 Gaucher. This Phase 1/2 trial (NCT04145037), named GAU-201, is recruiting patients at University of Calgary in Canada. (More information about study location is available here.)

The trial’s start follows last year’s clearance by Health Canada. Additional study sites are planned to open in Australia and other countries in 2020, pending regulatory clearances.

The trial is designed to enroll eight to 16 patients age 16 to 35, and will include both untreated patients and those on stable enzyme replacement therapy.

Participants will receive a single treatment with AVR-RD-02 and will be followed for one year. Efficacy outcome measures include liver and spleen volumes, hemoglobin values, platelet counts, bone pain and bone density measures, and  other blood markers.

Orphan status qualifies Avrobio for several incentives intended to support clinical trials of AVR‑RD‑02 and, if approved, its commercialization.

“Under the existing standard of care, patients with Gaucher disease are bound to a lifelong infusion schedule of enzyme replacement therapies, and still experience painful and progressive symptoms such as debilitating musculoskeletal pain and fatigue,” Birgitte Volck, MD, PhD, said in a press release. Volck is Avrobio’s president of research and development,

“Orphan-drug designation recognizes the unmet need of populations with rare diseases like Gaucher where Avrobio strives to transform lives by addressing the underlying cause of the disease with a single dose of gene therapy,” she said.

People with Gaucher disease have a faulty GBA gene, which results in impaired activity of the enzyme beta-glucocerebrosidase (GCase) and accumulation of lipid (fat) called glucosylceramide in cells.

AVR-RD-02 is designed to genetically modify the patient’s own blood-forming (hematopoietic) stem cells to produce a working GCase. It delivers a fully functional copy of the GBA gene into hematopoietic stem cells collected from patients. Those cells then are reintroduced into the patient’s body.

The ultimate goal is to provide durable and potentially life-long therapeutic benefit by restoring the capacity of tissues to produce sufficient amounts of GCase.

The gene therapy uses plato platform, Avrobio’s automated cell manufacturing technology that consists of a harmless lentiviral vector to deliver the target gene.

Preclinical studies backed the approach’s potential. In mouse models of Gaucher disease, AVR-RD-02 increased the activity of GCase across clinically relevant tissues, including bone marrow, spleen, liver, and thymus.

Importantly, this resulted in reversal of disease manifestations such as spleen enlargement, restoration of blood values, and less infiltration of Gaucher cells in the bone marrow.

Besides Gaucher disease, Avrobio is pursuing gene therapy programs for other rare lysosomal storage disorders, including Fabry disease, cystinosis, and Pompe disease.