Clinical Trial – Investigational Gene Therapy for Cystinosis.

Reduction in number of cystine crystals as measured in skin and intestinal mucosa biopsies observed across first three patients.

Investigational Gene Therapy for Cystinosis.

AVROBIO, a leading clinical-stage gene therapy company with a shared purpose to free people from a lifetime of genetic disease, today reported interim data from a collaborator-sponsored, ongoing Phase 1/2 clinical trial of AVR-RD-04, an investigational gene therapy for cystinosis, at the 18th Annual WORLD Symposium in San Diego.

The first three patients infused with AVR-RD-04 remain off oral cysteamine, with follow up durations ranging between 12- and 26-months post-gene therapy infusion. Sustained engraftment has been observed in each of these patients, as demonstrated by stable vector copy number (VCN) levels. A fourth patient was infused in November 2021. No adverse events related to the drug product have been reported in the four patients infused to date.

“The significant unmet need of people living with cystinosis remains the compelling impetus for the development of new treatments. Under existing drug regimens that are both burdensome and frequently carry substantial side effects, patients still face relentless disease progression and the prospect of debilitating symptoms, kidney transplantation with life-long immunosuppression therapy and significantly shortened lives,” said AVROBIO President and CEO, Geoff MacKay. “These interim data increase our confidence in the safety and efficacy of our gene therapy approach using the patient’s own hematopoietic stem cells and lay the groundwork for the AVROBIO-sponsored clinical trial for cystinosis planned to begin in 2023.”


Data support engraftment and potential durability with reduction in symptoms

The collaborator-sponsored Phase 1/2 clinical trial is evaluating the safety and efficacy of AVR-RD-04 in adult patients who previously had been treated with cysteamine. AVR-RD-04 consists of the patient’s own hematopoietic stem cells, genetically modified to express functional cystinosin, the protein that is deficient in people living with cystinosis.

Interim VCN data indicate that the first three patients dosed have potentially reached a plateau 12- to 26-months post-gene therapy infusion at levels between 1 and 2.6 VCN per diploid genome (dg). VCN/dg is the average number of copies of the transgene integrated into the cell genome and is used to help assess the long-term engraftment and thus durability of gene therapy.

Skin and intestinal mucosa biopsies for the first three patients infused indicate a decline in the number of cystine crystals, with one-year reductions in average intracytoplasmic crystals per cell in skin ranging from 35% in patient 1, 64% in patient 2 and 81% in patient 3. In rectal biopsies, a 53% reduction was observed in patient 1 after 18 months, and 28% and 86% reductions were observed in patients 2 and 3, respectively, after 12 months. A hallmark of cystinosis is the accumulation of cystine in lysosomes, a type of cellular organelle, which leads to tissue and organ damage resulting in debilitating co-morbidities.

“Although this is interim data, we believe that the favorable safety profile observed to date, combined with sustained engraftment and consistent data across multiple other clinical measures, establish proof-of-concept in adult patients, and support our view that gene therapy using a patient’s own hematopoietic stem cells given as a single infusion has the potential to be effective against this devastating disease,” said AVROBIO Chief Medical Officer, Essra Ridha, M.D.

No adverse events related to drug product

Safety data from the four patients dosed to date indicate no adverse events (AEs) related to drug product. All adverse events were related to myeloablative conditioning, stem cell mobilization, underlying disease, or pre-existing conditions. Most of AEs were mild or moderate and resolved without clinical sequelae.


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