FDA Pushes Rocket’s LAD-I Gene Therapy PDUFA for CMC Review
Rocket submitted additional CMC data in response to FDA information requests.
Donald B. Kohn, MD
Credit: UCLA
The FDA has extended its priority review for Rocket Pharmaceuticals’ Kresladi (marnetegragene autotemcel; RP-L201) gene therapy for treating leukocyte adhesion deficiency-I (LAD-I), pushing back the therapy’s Prescription Drug User Fee Act (PDUFA) date from March 31, 2024, to June 30.1
“We look forward to continuing our close collaboration with the FDA and together share a deep sense of responsibility in the rigorous process required to bring novel, potentially curative gene therapies, like KRESLADI™ to patients who need them most,” Gaurav Shah, MD, Chief Executive Officer, Rocket Pharma, said in the company’s update.1 “We remain confident and focused on making this therapy available for patients as quickly as possible.”
The FDA shared that the delay will serve to allow additional time to review clarifying Chemistry, Manufacturing, and Controls (CMC) information submitted by Rocket in response to FDA information requests. An advisory committee meeting will not be needed, the agency confirmed.
Kresladi consists of autologous hematopoietic stem cells transduced with a lentiviral vector to deliver a functional copy of the ITGB2 gene, which is the mutated gene in LAD-I. ITGB2 encodes for the beta-2 integrin component CD18 that facilitates leukocyte adhesion and enables their extravasation from blood vessels to fight infection. The therapy has received Regenerative Medicine Advanced Therapy (RMAT), Rare Pediatric, and Fast Track designations in the United States, PRIME and Advanced Therapy Medicinal Product (ATMP) designations in the European Union, and Orphan Drug designations in both.
Rocket previously announced that its biologics license application (BLA) for Kresladi was accepted with priority review in October 2023.2
“As the Principal Investigator in the US, I oversaw treatment of 6 of the 9 LAD-I patients in this trial. In my opinion, the results are remarkable. All of these children have been in good health with no significant LAD-I-related infections or inflammatory skin lesions since treatment. Based on what I see, they are all experiencing a normal childhood life, which is the goal of this type of potentially curative gene therapy,” Donald B. Kohn, MD, Distinguished Professor of Microbiology, Immunology & Molecular Genetics, Pediatrics, and Molecular & Medical Pharmacology, University of California, Los Angeles (UCLA) and director, UCLA Human Gene and Cell Therapy Program, said in a statement about the BLA acceptance.2
Kresladi has demonstrated efficacy in children with LAD-I in a global phase 1/2 trial (NCT03812263), positive topline results from which were presented by Kohn at the 2023 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held February 15-18 in Orlando, Florida.
The data boasted a 100% overall survival rate in patients for at least 1 year of follow-up and up to 2 years of age without hematopoietic stem cell transplantation in 9 patients, meeting the trial’s primary endpoint. Investigators observed genotypic and phenotypic correction, durable for up to 36 months of follow-up, spontaneous resolution of skin rash related to LAD-1, and restoration of wound repair capabilities without infections typical of LAD-1 since treatment.3
