Hematopoietic Cell-based Gene Therapy Shows Durable Response in Fanconi Anemia


Long-term hematologic stability has been observed in at least 6 out of 10 patients with at least 12 months of follow-up.

Patients with Fanconi anemia who received treatment with an investigational hematopoietic cell-based gene therapy carrying the FANCA gene saw durable responses through more than 12 months of follow-up. Updated results from 10 patients with a least 1 year of follow-up were presented at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023.

Although hematopoietic stem cell transplant typically results in over an 80% survival rate, the therapy is associated with serious adverse effects, including 100-day mortality and an increased risk of malignancies. To address this, investigators are evaluating a gene therapy that utilizes autologous Fanconi anemia Group A CD34+ enriched hematopoietic stem and progenitor cells that engraft without the use of antecedent conditioning. The therapy, RP-L102, developed by Rocket Pharmaceuticals, is currently in phase 1/2 clinical trials (NCT03814408; NCT03157804).

As of the October 2022 data cutoff, 12 patients at least 1 year of age with no HLA-matched sibling donor have been treated and followed to assess phenotypic correction, engraftment, clinical response, and safety of RP-L102. In at least 6 out of 10 patients with at least 12 months of follow-up, investigators observed phenotypic correction via sustained increase in bone marrow colonyformingcells marrow mononuclear cells (BM CFC MMC) resistance, concomitant genetic correction and hematologic stabilization, all of which was achieved in the absence of conditioning. Among the 6 patients with BM MMC resistance of at least 20% (range, 51%-94%), concomitant blood count stabilization was observed over 12- to 36-month follow-up.Notably, long-term hematologic stability has been observed in 2 patients with up to 6 years of follow-up post-treatment with RP-L102. In 7 of 10 patients with at least 1 year of follow-up, progressive increases and sustained genetic correction have been observed in peripheral blood (range, 0.35-0.58) and bone marrow (range, 0.17-1.03).

The overall safety profile has been highly favorable, with no reports of BM dysplasia, clonal dominance or insertional mutagenesis related to the treatment. One patient experienced a grade 2 transient infusion-related reaction that resolved without any further clinical sequelae. Notably, 1 patient who did not demonstrate genetic correction and experience progressive BM failure successfully underwent allogeneic hematopoietic stem cell transplantation, and 1 patient was diagnosed with T-cell lymphoblastic lymphoma at approximately 22 months post-treatment, but the malignancy was determined to be unrelated to treatment with RP-L102.

With a total treatment time of about 2 weeks with no harsh conditioning and the risks associated with it, treatment with RP-L102 is a “very easy treatment compared with allo-transplant protocols,” principal investigator Agnieszka Czechowicz, MD, PhD, assistant professor of pediatrics at Stanford University, said during her presentation.

For more coverage of the 2023 Tandem Meetings, click here.

Czechowicz A, Sevilla J, Agarwal R, et al. Lentiviral-Mediated Gene Therapy for Patients with Fanconi Anemia [Group A]: Updated Results from Global RP-L102 Clinical Trials. Presented at: 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR. February 15-19, 2023; Orlando, FL. Abstract 113
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