RARE Daily

Rocket Reports Positive Top-line Data from Severe Leukocyte Adhesion Deficiency-I Program

May 20, 2022

Rocket Pharmaceuticals, a company advancing a pipeline of genetic therapies for rare childhood disorders with high unmet need, reported positive top-line safety and efficacy data from its phase 2 pivotal trial for severe leukocyte adhesion deficiency-I (LAD-I) at the 25th Annual Meeting of the American Society of Gene and Cell Therapy.

Photo: Gaurav Shah, CEO of Rocket

Photo: Gaurav Shah, CEO of Rocket Pharmaceuticals

“The positive top-line safety and efficacy data from the phase 2 pivotal trial for LAD-I represents a significant step forward in the development of RP-L201 for the treatment of leukocyte adhesion deficiency-I (LAD-I), one of the most aggressive and highly fatal immunodeficiencies ever characterized,” said Gaurav Shah, CEO of Rocket Pharma. “Moreover, they point to the great possibilities lentiviral-based gene therapies can offer for patients with devastating diseases.”

The oral presentation includes efficacy and safety data (cut-off March 9, 2022) at three to 24 months of follow-up after RP-L201 infusion for all patients and overall survival data for seven patients at 12 months or longer after infusion. All patients, aged five months to nine years, demonstrated sustained CD18 restoration and expression on more than 10 percent of neutrophils (median: 56 percent).

The data showed 100 percent overall survival in patients at one year post RP-L201 infusion, based on Kaplan-Meier estimate. All nine patients with three to 24-months of available follow-up also showed clinical reversal of disease course, including statistically significant reduction in all-cause hospitalizations and incidence of severe infections, and evidence of resolution of LAD-I-related skin rash and restoration of wound repair capabilities.

Severe leukocyte adhesion deficiency-I (LAD-I) is a rare, autosomal recessive pediatric disease caused by mutations in the ITGB2 gene encoding for the beta-2 integrin component CD18. CD18 is a key protein that facilitates leukocyte adhesion and extravasation from blood vessels to combat infections. As a result, children with severe LAD-I are often affected immediately after birth. During infancy, they suffer from recurrent life-threatening bacterial and fungal infections that respond poorly to antibiotics and require frequent hospitalizations. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. Without a successful bone marrow transplant, mortality in patients with severe LAD-I is 60-75 percent prior to the age of 2 and survival beyond the age of 5 is uncommon. There is a high unmet medical need for patients with severe LAD-I.

RP-L201 is an experimental lentiviral-mediated ex vivo gene therapy being developed for severe LAD-I. The therapy consists of hematopoietic stem cells from the patient that have been genetically modified with a lentiviral vector to contain a functional copy of the ITGB2 gene. RP-L201 is currently being evaluated in a phase 1/2 clinical trial. The interim analysis of the trial at three to 24 months of follow-up showed RP-L201 had a favorable safety profile and evidence of efficacy with durable CD18 expression.

“While allogeneic transplant options are available, they continue to be associated with considerable toxicity and today’s top-line safety and efficacy data point to the potential of RP-L201 to change the treatment paradigm for patients living with severe LAD-I,” said Shah. “These results are a testament to the LAD-I patient community and focus of the Rocket team on steady, reliable execution. Based on these results, we are initiating discussions with health authorities on filing plans and anticipate filings in the first half of 2023.”

Rocket’s LAD-I research is made possible by a grant from the California Institute for Regenerative Medicine.

Author: Rare Daily Staff

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