Serious and life-threatening infections experienced by people with a rare immune disorder called leukocyte adhesion deficiency — I mean, some babies don’t survive beyond infancy. Of those who did, most did not live past their fifth birthday. Clinical data from Rocket Pharmaceuticals’ gene therapy for the disease suggest that it could not only address the underlying genetic problem, but also help patients live longer.
Rocket present Based on the results, the biotech said it is in discussions with regulators and expects to submit an application for approval in the first half of next year, according to preliminary data Thursday at the American Society for Gene and Cell Therapy annual meeting in Washington, D.C.
serious Leukocyte Adhesion Defect-I (LAD-I) is a rare inherited immune disorder caused by mutations in ITGB2, the gene encoding CD18, a protein important for helping white blood cells adhere to blood vessels. Children born with LAD-I are more susceptible to repeated bacterial and fungal infections that can be life-threatening. Antibiotics are often ineffective in these patients, and they develop infections that require frequent hospitalization. Hematopoietic stem cell transplantation offers a curative treatment option, but the procedure itself carries the risk of life-threatening complications, meaning it is only suitable for the most severe cases.
Rocket’s gene therapy, RP-L201, is made from a patient’s hematopoietic stem cells. These cells were engineered using lentiviral vectors to carry a functional copy of the ITGB2 gene. Using a patient’s own stem cells avoids the need to find a matched donor, as is required for hematopoietic stem cell transplants. This approach also promises to reduce toxicity compared to transplantation using donor cells.
The open-label Phase 1/2 clinical trial enrolled 9 children 3 months of age and older. Similar to the preparation required for stem cell transplants, patients in the study underwent a conditioning regimen to prepare their bodies for the experimental Rocket treatment. The primary goals of the Phase 2 portion of the study were to measure the proportion of patients who were still alive one year after receiving gene therapy, as well as the number of participants who experienced treatment-related adverse events. Measuring CD18 expression was a secondary objective.
As of the March 9 deadline, Cranbury, NJ-based Rocket had patient data from 3 to 24 months of follow-up after the infusion. The company reported that all nine patients showed sustainable CD18 expression on neutrophils, a type of white blood cell. The median CD18 expression was 56%. For the seven patients who had reached the 12-month mark after infusion, the overall survival rate was 100%. Additionally, Rocket reported a statistically significant reduction in hospitalizations for all nine patients. The company also said that patients showed regression of rashes and recovery of wound repair ability.
Rocket reported no treatment-related serious adverse events. Conditioning regimens, including the chemotherapy busulfan, do have side effects, including nausea, vomiting, and diarrhea. The adverse effects of these related procedures are consistent with the safety of busulfan and pretreatment procedures, Rocket said.
“While there are allograft options, they are still associated with considerable toxicity, and today’s top safety and efficacy data suggest that RP-L201 has the potential to change the treatment paradigm for patients with severe LAD-I,” Gaurav Shah, Rocket’s CEO, said in a prepared statement.
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