Cystinosis Gene Therapy Trial in Full Swing


The trial is being conducted at the University of California – San Diego under the leadership of Stephanie Cherqui, PhD.

AVROBIO has dosed the sixth and final patient in its phase 1/2 trial (NCT03897361) of AVR-RD-04, an investigative gene therapy for cystinosis.

The trial is being conducted by University of California – San Diego (UCSD) and is funded in part by grants from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH). The trial is being run by principal investigator Stephanie Cherqui, PhD, associate professor of pediatrics at UCSD, with whom CGTLive previously discussed the trial with back in July. AVROBIO plans to initiate a company-sponsored trial in 2023.

“Completing the dosing of the first and only gene therapy trial for cystinosis represents a major milestone for a patient community living with a devastating genetic disease. Unmet medical needs impact the lives of patients and their family members every day,” Cherqui said in a statement. “To date, the results from the trial show the potential of this investigational gene therapy to stabilize or reduce the impact of cystinosis on different tissues throughout the body with a one-time dose.”

AVR-RD-04 is developed by gene-editing patients’ hematopoietic stem cells (HSC) ex vivo to express a corrected cystinosin gene to restore metabolism of cystine via a lentiviral vector (either pCCL-CTNS or pCDY.EFS.CTNS.T260I). The therapy has been granted rare pediatric disease, fast track, and orphan drug designations by the FDA, the latter of which was also granted by the EMA.

WATCH NOW: Assessing Lentiviral Cell Therapy for Cystinosis: Stephanie Cherqui, PhD

The 6 participants in the trial are in 3 cohorts of 2 each, with participants in the first 2 cohorts at least 18 years of age and participants in the third cohort at least 14 years of age. Participants underwent HSC mobilization and leukapheresis. HSCs are then modified to express the cystinosis gene. Participants are treated with busulfan for marrow cytoreduction before infusion. During the trial, participants discontinue cysteamine during the assessment period and are evaluated at 3-, 6-, 12-, 18-, and 24-months after infusion and are then eligible for a 15-year long-term follow-up study.

Data from the first 5 patients in the trial seem to show that the therapy is well-tolerated, with investigators observing no adverse events (AEs) related to treatment to date. AEs that did occur were mostly mild/moderate, resolved without clinical sequelae and were related to myeloablative conditioning, study procedures, underlying disease or preexisting conditions. Preliminary efficacy data suggest that AVR-RD-04 has a therapeutic effect in eye, skin, gastrointestinal mucosa, andother tissues as well as the neurocognitive system.

The trial is primarily evaluating safety and tolerability of AVR-RD-04, including incidence and severity of AEs, replication-competent lentivirus, genotoxicity, and event-free survival. Secondary outcome measures include preliminary efficacy, including change in cystine levels and effects on clinical disease outcomes such as kidney function, vision, muscle strength, pulmonary function, and neurological and psychometric function, as well as quality of life.

“With proof-of-concept demonstrated, we continue to lay the groundwork for an AVROBIO-sponsored clinical trial planned to begin in 2023,” Essra Ridha, MD, MRCP, FFPM, chief medical officer, AVROBIO, added to the statement. “We look forward to our interactions with regulators on our clinical and Chemistry Manufacturing and Controls (CMC) strategy.”

AVROBIO announces completion of patient dosing in first gene therapy clinical trial for cystinosis. News release. AVROBIO. October 25, 2022.
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