AVR-RD-02 is a gene therapy candidate that Avrobio is developing as a potential treatment for Gaucher disease.

A trial testing the therapy in patients with type 1 Gaucher is currently underway in Canada and Australia, and is now recruiting participants. Health Canada had cleared Avrobio’s application to conduct a clinical trial of AVR-RD-02 beginning in 2019.

How does AVR-RD-02 work?

Gaucher disease is a metabolic condition caused by mutations in the GBA gene. This gene carries the instructions necessary for cells to make the beta-glucocerebrosidase enzyme, which is essential for the breakdown of the fat molecule glucocerebroside. The mutations lead to insufficient levels of beta-glucocerebrosidase. The result is the build-up of glucocerebroside in various organs and tissues. 

AVR-RD-02 delivers a healthy copy of the GBA gene to the body. The aim is to restore the proper synthesis and activity of the beta-glucocerebrosidase enzyme.

First, hematopoietic stem cells are collected from the patient and modified in the laboratory to carry a healthy copy of the GBA gene. A genetically altered virus that does not cause disease delivers the gene to the stem cells. The modified stem cells carrying the healthy GBA gene are then reintroduced into the patient’s body.

Researchers used a mouse model of Gaucher to assess the efficacy of AVR-RD-02 in preventing and reversing the symptoms of the disease. The mice lacked the GBA gene and mimicked Gaucher disease in patients. The study found high levels of beta-glucocerebrosidase in mice treated with AVR-RD-02, which helped in the clearance of glucocerebroside from the spleen and in reducing swelling.

Steady levels of the enzyme also were detected in other organs and tissues, such as the liver and bone marrow, correlating with a reduction in glucocerebroside levels at these sites. The treatment also prevented the progression of the disease.

AVR-RD-02 in clinical trials

Avrobio is now recruiting type 1 Gaucher patients for a Phase 1/2 clinical trial, called GuardOne (NCT04145037), that is testing the safety and efficacy of AVR-RD-02. Up to 16 patients, ages 16 to 35, can enroll at trial sites in Canada or Australia. The company also plans to open sites in the U.S.

A single infusion of AVR-RD-02 will be given to participants after a baseline period, at the study’s start, of up to three days and a pre-transplant period of six to eight weeks. Investigators will monitor patients for a year after the infusion. The participants will then be transferred into another study, which will follow them for an additional 14 years.

The researchers will monitor beta-glucocerebrosidase levels and activity, spleen and liver volume, and bone mineral density to assess the treatment’s efficacy. Safety will be assessed throughout the trial. Finally, the study will monitor the treatment’s impact on the participants’ quality of life.

Avrobio announced three-month results for the first patient who received AVR-RD-02 treatment. The patient showed a 22% reduction in the levels of glucosylsphingosine (lyso-GB1) compared with baseline while receiving enzyme replacement therapy (ERT). Researchers often use lyso-GB1 as a diagnostic biomarker for Gaucher disease.

The patient also had a 17% decrease in blood levels of chitotriosidase. Chitotriosidase is a biomarker for activated macrophages — a type of immune cell, also referred to as “Gaucher cells” — that can cause damage to different organs. The patient discontinued ERT a month before the AVR-RD-02 infusion and had not resumed it during those three months of the trial. Researchers reported no serious adverse events.

The trial is due to conclude in September 2022, with top-line data expected by May of this year.

Other information

The U.S. Food and Drug Administration granted orphan drug designation to AVR-RD-02 as a treatment for Gaucher in October 2019. AVR-RD-02 also received orphan drug designation from the European Union in October 2020.


Last updated: Jan. 25, 2020


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