FDA Rejects Rocket's Gene Therapy for Immune Disorder Due to Manufacturing Issues

The US Food and Drug Administration (FDA) has decided not to approve Rocket Pharmaceutical’s gene therapy, Kresladi (marne-cel), at this time, requesting additional information about its manufacturing processes. This decision was communicated through a complete response letter (CRL), which causes a delay in the approval process for the therapy designed to treat severe cases of leukocyte adhesion deficiency-I.

Rocket Pharmaceuticals had anticipated that the FDA would reach a decision by March 2024. However, the agency extended the review period by three months to thoroughly examine supplemental chemistry, manufacturing, and controls (CMC) information. Consequently, the FDA’s CRL has asked Rocket Pharmaceuticals to provide "limited additional" CMC information.

When Rocket Pharmaceuticals disclosed this development on 28 June, its shares initially fell by 11% but eventually recovered by the end of the trading day. Rocket has already met with the FDA to agree on the specific additional information needed to expedite the approval process for Kresladi.

Leukocyte adhesion deficiency-I is an uncommon genetic immune disorder that renders patients highly susceptible to recurrent infections. Patients with this condition lack the protein-encoding ITGB2 gene, which prevents their white blood cells from adhering to the vascular endothelium and migrating to infection sites. This disorder can lead to severe complications, and without a successful bone marrow transplant, survival beyond childhood is rare. The precise incidence of leukocyte adhesion deficiency-I in the general population remains unknown.

Rocket Pharmaceuticals reported a 100% overall survival rate in a global Phase I/II study conducted 12 months after the infusion of Kresladi. The trial achieved all primary and secondary endpoints without any treatment-related serious adverse events. Kresladi's mechanism involves engineering hematopoietic stem cells taken from the patient. Using a genetically modified lentiviral vector (LV), Rocket inserts a functional copy of the ITGB2 gene into these cells.

The delayed approval review also means that Rocket Pharmaceuticals will have to wait to receive a priority review voucher, which is awarded for therapies reviewed under the expedited rare pediatric designation program. Once approved through this pathway, the company would receive the voucher.

Furthermore, Rocket Pharmaceuticals is awaiting an approval decision on another gene therapy candidate, RP-L102. This therapy, also based on the LV vector, is currently under review by the European Medicines Agency for the treatment of Fanconi anaemia, a rare bone marrow disorder.

Rocket Pharmaceuticals expressed optimism, emphasizing their alignment with the FDA on the limited scope of additional CMC information needed to support the approval of Kresladi as promptly as possible. This collaboration aims to accelerate the availability of Kresladi to patients in need, pending the FDA’s requirements.

In summary, the FDA's request for more information has temporarily halted the progress of Kresladi, Rocket Pharmaceuticals' gene therapy for leukocyte adhesion deficiency-I. The company remains committed to working closely with the FDA to meet the necessary requirements and expedite the approval process for this potentially life-saving therapy.