AVR-RD-02 is a gene therapy candidate being developed by Avrobio as a potential treatment of Gaucher disease.
Avrobio’s application to conduct a Phase 1/2 clinical trial of AVR-RD-02 in patients was cleared by Health Canada in October 2018, permitting the company to open studies.
The U.S. Food and Drug Administration (FDA) granted an orphan drug designation to AVR-RD-02 as Gaucher treatment in October 2019.
How does AVR-RD-02 work?
Gaucher disease is a metabolic condition caused by mutations in the GBA gene that carries the instructions to make beta-glucocerebrosidase, an enzyme required for the breakdown of the fat molecule glucocerebroside. The mutations cause insufficient levels of beta-glucocerebrosidase to be made, resulting in the build-up of glucocerebroside in various organs and tissues, which leads to the symptoms of Gaucher disease.
AVR-RD-02 is designed to deliver a healthy copy of the GBA gene to the patient, restoring the proper synthesis and activity of the beta-glucocerebrosidase enzyme. Hematopoietic stem cells are first 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 is used to deliver the gene to the stem cells. The modified stem cells carrying the healthy GBA gene are then reintroduced into the patient’s body.
The goal is to allow the body to produce sufficient amounts of beta-glucocerebrosidase, reversing the effects of the deficiency of this enzyme in patients.
AVR-RD-02 in clinical trials
Researchers used a mouse model of Gaucher disease to assess the efficacy of AVR-RD-02 in preventing and reversing the clinical symptoms of the disease. The mice used in the study lacked the GBA gene and mimicked Gaucher disease seen 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 reversing swelling. Steady levels of the enzyme were also detected in other organs, such as the animals’ liver and bone marrow, which also correlated with a reduction in glucocerebroside levels at these sites. The treatment prevented the progression of the disease.
Avrobio is now recruiting patients with type 1 Gaucher disease for a Phase 1/2 clinical trial (NCT04145037) in Canada testing the safety and efficacy of AVR-RD-02. Up to 16 patients, ages 16 to 35, will be enrolled at its single site in Alberta; information is available here. Beta-glucocerebrosidase levels and activity, spleen and liver volume, and bone mineral density will be monitored to assess the treatment’s efficacy; safety will be assessed throughout.
The team will also monitor the treatment’s impact on patients’ quality of life. This trial is due to conclude in September 2022.
Last updated: Nov. 11, 2019
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