Rocket gene therapy's flight to approval delayed by FDA rejection over manufacturing questions

Rocket Pharmaceuticals’ flight path to approval for Kresladi has been delayed again after the FDA issued a complete response letter (CRL) requesting additional manufacturing information.

The biotech submitted an application in October 2023 for the gene therapy, which is also known as marnetegragene autotemcel or marne-cel, to treat severe leukocyte adhesion deficiency-I. The therapy contains patient-derived hematopoietic stem cells that have been genetically modified with an LV vector to deliver a functional copy of the ITGB2 gene.

Rocket had initially been expecting the FDA to make a decision by the end of March. But in February, the company revealed that the agency had pushed back the deadline until the end of June “to allow additional time to review clarifying Chemistry, Manufacturing, and Controls (CMC) information submitted by Rocket in response to FDA information requests.”

Now, the New Jersey-based biotech says it has a received a CRL from the FDA requesting “limited additional CMC information to complete its review.”

The company has already met with senior leaders from the FDA’s Center for Biologics Evaluation and Research (CBER) to “align on the limited scope of additional CMC information needed to support the approval of Kresladi as quickly as possible,” it said in the June 28 release.

“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,” Rocket’s CEO Gaurav Shah, M.D., said in the release. “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.”

Leukocyte adhesion deficiency-I is a rare genetic immune disorder that predisposes patients to recurrent infections and is almost always fatal in childhood without an allogeneic hematopoietic stem cell transplant. Rocket’s approval application for Kresladi was based on a phase 1/2 study of nine patients who were all alive 12 months after their infusions.

Rocket has a lot riding on Kresladi making a safe landing with regulators. In May, the biotech said it is continuing to “ramp up enabling activities to support the launch of its LV vector portfolio, beginning with Kresladi.”

“Qualified Treatment Center initiation, disease education, payer engagement, and field team build-out are all underway,” the company added at the time.

Rocket’s stock was trading down 12.5% at $18.75 in pre-market trading Friday morning from a Thursday closing price of $21.43.

The company has another asset awaiting a regulator’s decision in RP-L102. The LV vector-based gene therapy is being considered by the European Medicines Agency to treat a rare genetic disorder called Fanconi anemia. An application to the FDA was also expected in the first half of 2024, but Rocket has yet to announce this has been submitted.

Analysts at William Blair said they were "disappointed" by news of the CRL, but "ultimately believe the company will quickly resolve the request for limited additional CMC information and resubmit the [biologics license application] in a timely manner."

"Since we believe the CRL is mainly due to a lack of reviewer continuity, we do not see any read-through to the company’s other clinical programs and highlight the BLA submission for RP-L102 remains on track for the first half of 2024," the analysts added in a June 28 note.