AVR-RD-01 Gene Therapy Granted Orphan Drug Status in EU

The European Commission has granted orphan drug designation to Avrobio’s investigational gene therapy AVR-RD-01 for the treatment of Fabry disease.

The decision, based on a positive opinion from the Committee for Orphan Medicinal Products of the European Medicines Agency, will provide regulatory and financial incentives for the company to develop and market the therapy, and is typically granted to medicines to treat or prevent life-threatening or rare chronic diseases.

“We are delighted to receive this orphan drug designation and look forward to advancing our investigational gene therapy for people living with Fabry disease,” Geoff MacKay, president and CEO of Avrobio, said in a press release.

Fabry disease is caused by a defect in the GLA gene, resulting in the deficiency of the enzyme alpha-galactosidase A (AGA). This enzyme is essential for the breakdown of a type of fat called globotriosylceramide (Gb3), which accumulates in various cells throughout the body, causing the progressive clinical signs and symptoms associated with Fabry.

AVR-RD-01 is a cell-based therapy that uses a patient’s modified hematopoietic stem cells — which give rise to other blood and immune cells — to produce a functional AGA enzyme.

Researchers use an engineered harmless viral vector to carry a functional version of the GLA gene and introduce it into harvested stem cells from a patient before these are reinserted back into the patient.

“Our investigational gene therapy is designed to mimic the body’s natural ability to produce alpha-galactosidase A enzymes and to reach all organs, including the brain,” MacKay said.

AVR-RD-01 is currently being tested in the Phase 2 clinical trial FAB-GT (FAB-201, NCT03454893). The multinational, open-label trial is evaluating the efficacy and safety of AVR-RD-01 in eight to 12 males, age 16 and older. The trial is currently recruiting, and more information can be found here.

Study participants must have a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity and must not have received treatment with enzyme replacement therapy within the past 10 years and/or chaperone therapy at the time of screening.

The study is broken into different parts: an initial screening and assessment, a pre-transplant period in which patients will receive treatment for four weeks to partially suppress their bone marrow from producing blood cells (a process called myeloablation), gene therapy administration, and post-transplant follow-up for 48 weeks whereby safety and efficacy assessments will be performed.

Once the study is completed, patients will be followed for up to 15 years to monitor the therapy’s efficacy and safety.

Despite a temporary pause in enrollment due to the ongoing pandemic, Avrobio continues to identify eligible patients in Australia, Canada, and the U.S.

So far, preliminary results of a Phase 1 and Phase 1/2 trial have shown that AVR-RD-01 was well-tolerated and showed sustained efficacy in the treatment of Fabry disease.

The therapy has also received orphan drug designation in the U.S.