FDA Rejection Delays Rocket Gene Therapy Approval Due to Manufacturing Questions

Rocket Pharmaceuticals has encountered another setback in its quest for approval of Kresladi, a gene therapy designed to treat severe leukocyte adhesion deficiency-I. The U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL), requesting more information regarding the manufacturing processes for Kresladi.

The biotech company initially submitted its application for the therapy, also known as marnetegragene autotemcel or marne-cel, in October 2023. This gene therapy aims to treat severe leukocyte adhesion deficiency-I by using patient-derived hematopoietic stem cells genetically modified with a lentiviral (LV) vector to introduce a functional copy of the ITGB2 gene. This disorder is a rare genetic immune deficiency that makes patients highly susceptible to recurrent infections and is often fatal in childhood if not treated with an allogeneic hematopoietic stem cell transplant.

Rocket had anticipated an FDA decision by the end of March, but the agency extended the deadline to the end of June to review additional clarifying information on Chemistry, Manufacturing, and Controls (CMC) submitted by Rocket. Now, the FDA has issued a CRL requesting “limited additional CMC information” to complete its review.

Rocket Pharmaceuticals has already engaged in discussions with senior officials from the FDA’s Center for Biologics Evaluation and Research (CBER) to outline the specific additional CMC information required. The company expressed confidence that this collaboration would expedite the approval process. "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," said Rocket’s CEO, Gaurav Shah, M.D., in a recent statement.

Data supporting Rocket’s application for Kresladi came from a phase 1/2 clinical trial involving nine patients, all of whom were alive 12 months post-infusion. Given the high stakes, Rocket has been ramping up its efforts to prepare for the potential launch of Kresladi. These preparations include initiating Qualified Treatment Centers, conducting disease education, engaging with payers, and expanding their field team.

The delay has had a financial impact, with Rocket’s stock dropping 12.5% to $18.75 in pre-market trading on Friday morning, down from a Thursday closing price of $21.43.

Rocket is also awaiting regulatory decisions on another gene therapy asset, RP-L102, designed to treat Fanconi anemia, a rare genetic disorder. This therapy is currently under review by the European Medicines Agency, and an application to the FDA is anticipated in the first half of 2024.

Despite the setback, analysts at William Blair remain optimistic about Rocket’s future. They expressed disappointment over the CRL but believe that Rocket will be able to address the FDA's request promptly and resubmit its biologics license application (BLA) in a timely manner. The analysts also noted that they do not anticipate this issue affecting the company's other clinical programs and expect the BLA submission for RP-L102 to stay on schedule for the first half of 2024.

In summary, while Rocket Pharmaceuticals has faced a delay in its approval process for Kresladi, the company remains focused on resolving the FDA’s request for additional information. Rocket is actively preparing for the launch of its gene therapies and remains optimistic about meeting the unmet medical needs of patients with severe genetic disorders.