FDA Issues Complete Response Letter for Kresladi for Rare Immune Disorder

The FDA has issued a complete response letter for Rocket Pharmaceuticals’ Kresladi (marnetegragene autotemcel; marne-cel), a gene therapy to treat the rare, autosomal recessive pediatric disease leukocyte adhesion deficiency-I (LAD-I). Regulators are asking for additional chemistry manufacturing and controls (CMC) information to complete its review. CMC provides for measures to ensure quality and consistency during manufacturing.

Gaurav Shah, M.D.

Rocket Pharmaceuticals’ CEO Gaurav Shah, M.D., said in a news release that the company has met with officials from the FDA’s Center for Biologics Evaluation and Research (CBER) to determine what additional information is needed to support the approval of Kresladi.

Severe leukocyte adhesion deficiency-I is caused by mutations in the ITGB2 gene that encodes for CD18, a key protein that facilitates the immune response against infections. As a result, white blood cells (leukocytes) do not function normally. Children with this disease experience life-threatening bacterial and fungal infections that respond poorly to antibiotics. Children who survive infancy experience recurrent severe infections including pneumonia, gingival ulcers, necrotic skin ulcers, and septicemia. LAD-I is estimated to impact an estimated 800 to 1,000 children in the United States and Europe.

Kresladi is a lentiviral vector-based investigational gene therapy. It contains autologous hematopoietic stem cells that have been genetically modified to deliver a functional copy of the ITGB2 gene. Data from the global phase 1/2 study demonstrated 100% overall survival at 12 months post-infusion (and for the entire duration of follow-up) for all nine LAD-I patients with 12 to 24 months of available follow-up.

Related: FDA Extends Review of Gene Therapy for Rare Immune Disorder

In February 2024, the FDA had extended the review of Kresladi or regulators to review clarifying chemistry, manufacturing, and controls (CMC) information submitted by the company.

Last month, company officials said in their financial statement they are launch of Kresladi. They have begun to set up their network of qualified treatment centers, disease education, payer engagement and sales team.