FDA Issues CRL for Rocket’s LAD-I Gene Therapy


The FDA has requested limited additional CMC information.

The FDA has issued a complete response letter (CRL) to Rocket Pharmaceuticals’ marnetegragene autotemcel(RP-L201), to be marketed under the name Kresladi, for the potential treatment of leukocyte adhesion deficiency-I (LAD-I) due to a request for more Chemistry Manufacturing and Controls (CMC) information to complete its review.1

Rocket Pharma stated that it had met with FDA officials and aligned on the “limited” information requested.1 The CRL marks the second time the FDA has requested more CMC information, after the agency extended its priority review for Kresladi for treating, pushing back the therapy’s Prescription Drug User Fee Act (PDUFA) date from March 31, 2024, to June 30 to allow additional time to review clarifying information submitted by Rocket in response to FDA information requests.2

"It is reassuring to have the FDA as a close collaborator who understands the high unmet medical need, clear clinical benefit and importance of timely patient access," Gaurav Shah, MD, Chief Executive Officer, Rocket Pharma, said in a statement.1 "CBER leadership’s direct involvement and commitment to working expeditiously to deliver this therapy to patients gives us great hope on behalf of the primary immunodeficiency community."

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.

READ MORE: Rocket Pharmaceuticals Confirms Phase 2 Trial Plans for Danon Disease Gene Therapy With FDA

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

CGTLive previously spoke with primary investigator Donald B. Kohn, MD, distinguished professor of microbiology, immunology, molecular genetics, and pediatrics (hem/onc), and director, Human Gene Medicine Program at UCLA, about positive data from the trial.

"Outcomes from transplants other than sibling donors have bene much worse... so that’s the population of patients we’re [targeting] patients with a severe form of LAD-i who don’t have a matched donor," Kohn said.

Watch the full interview below:

1. Rocket Pharmaceuticals Provides Regulatory Update on KRESLADI™ (marnetegragene autotemcel; marne-cel). News release. Rocket Pharmaceuticals. June 28, 2024. https://finance.yahoo.com/news/rocket-pharmaceuticals-provides-regulatory-kresladi-112700392.html
2. Rocket Pharmaceuticals Announces Update on FDA Review Timeline of KRESLADI™ (marnetegragene autotemcel) for the Treatment of Severe Leukocyte Adhesion Deficiency-I (LAD-I). News release. Rocket Pharmaceuticals. February 13, 2024. https://www.biospace.com/article/releases/rocket-pharmaceuticals-announces-update-on-fda-review-timeline-of-kresladi-marnetegragene-autotemcel-for-the-treatment-of-severe-leukocyte-adhesion-deficiency-i-lad-i-/
3. Booth C, Sevilla J, Rao G, et al. Lentiviral-mediated ex-vivo gene therapy for pediatric patients with severe leukocyte adhesion deficiency-I (LAD-I): Interim results from an ongoing phase 1/2 study. Presented at: 2023 Tandem Meetings. Abstract #3
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