Gaucher Disease Gene Therapy Granted FDA Rare Pediatric Disease Designation


AVR-RD-02 also received ILAP designation in the UK earlier this month.

AVROBIO’s AVR-RD-02, an investigational gene therapy intended to treat Gaucher disease type 1, has received rare pediatric disease designation from the FDA.1

AVR-RD-02 is intended to modify patients’ hematopoietic stem cells (HSCs) to encode for functional human glucocerebrosidase (GCase). The therapy is currently being investigated in the phase 1/2 Guard1 clinical trial (NCT04145037) for patients with Gaucher disease type 1 (GD1). Early data from the first patient dosed in the trial, which had a cutoff of August 31, 2021, indicated promise in terms of safety and efficacy, with no adverse events (AEs) related to the gene therapy reported and the patient having remained off enzyme replacement therapy (ERT) at 14 months post-treatment.2 The therapy received Innovative Licensing and Access Pathway (ILAP) designation from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) earlier this month, and previously was granted fast track status by the FDA and orphan drug designation by both the FDA and the European Medicines Agency.3

“Many people with GD1 experience life-limiting symptoms even while on chronic enzyme replacement therapy. Our investigational therapy is designed to address these unmet needs with a single dose,” Geoff MacKay, president and chief executive officer, AVROBIO, said in a 2020 statement regarding AVR-RD-02.4 “We are eager to bring patients a fundamentally new approach with the potential to halt the progression of their disease and alleviate or even reverse symptoms not addressed by the standard of care.”

The open-label, multinational Guard1 study is expected to enroll 16 post-pubertal patients aged between 18 years and 50 years (inclusive) who have been diagnosed with GD1. Participants who are switch-stable are required to have received a stable dose of ERT between 15 U/kg and 60 U/kg (inclusive) every other week for at least 24 consecutive months with no significant interruptions, to have normal or near-normal hematologic values, and to have stable disease during the 6 months prior to screening. Participants who are treatment-naïve are required to have not received ERT for Gaucher disease in the year before screening and to have a hemoglobin level of less than or equal to 2 g/dL below the lower limit of normal with either an enlarged liver by palpation, a platelet count less than 120x109/L, or moderate splenomegaly by palpation. Participants with severe neurological signs and symptoms characteristic of neuronopathic Gaucher disease or tremor, peripheral neuropathy, or symptoms of Parkinson disease will be excluded from the study. Patients with a hemoglobin value below 9.0 g/dL, a platelet count less than 70x109/L, a spleen volume more than 10 times normal, or pulmonary hypertension will also be excluded. Additional exclusion criteria relate to patient health status, health history, and treatment history.

Patients will be assigned to either the switch-stable arm or the treatment-naïve arm, which will both follow a similar scheme; patients in the switch-stable arm must discontinue ERT at least 2 weeks before receiving treatment with AVR-RD-02. The study’s primary end points include the incidence of clinically significant AEs and serious AEs related to AVR-RD-02, the number of participants with clinically relevant abnormalities, the average vector copy number in peripheral blood and bone marrow, and the changes from baseline in spleen volume, liver volume, hemoglobin concentration, platelet count, and plasma lyso-Gb1 levels. Secondary end points include the change from average of screening and baseline over time in GCase enzyme activity, incidences of ERT used following AVR-RD-02 treatment, and the changes from baseline in bone mineral density, plasma Chitotriosidase activity levels, Bone Marrow Burden Score, and anti-GCase total antibodies and subsequent titers.

“We have multiple milestones planned for the second half of the year that will further inform the advancement of our pipeline,” McKay said in an August 2022 statement.6 “We plan to provide a comprehensive Gaucher disease franchise update in Q4 2022, including new clinical data from our Guard1 Phase 1/2 clinical trial for GD1, and updates on the clinical development and regulatory strategy for our GD type 3 program.”

1. AVROBIO receives rare pediatric disease designation from the U.S. FDA for first-in-class gene therapy for Gaucher disease. News release. AVROBIO, Inc. October 27, 2022. 
2. AVROBIO presents clinician experience with FAB-GT clinical trial and updated safety data for investigational gene therapies in Fabry disease and Gaucher disease type 1. News release. AVROBIO, Inc. November 24, 2021. 
3. AVROBIO granted ILAP designation from U.K. MHRA for first-in-class gene therapy for Gaucher disease. News release. AVROBIO, Inc. October 18, 2022. 
4. AVROBIO announces clinical and regulatory progress for gaucher disease program. News release. AVROBIO, Inc. January 14, 2020. 
5. AVROBIO reports second quarter 2022 financial results and provides business update. News release. AVROBIO, Inc. August 9, 2022.
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