The FDA rejected Rocket Pharmaceuticals’ gene therapy for leukocyte adhesion deficiency-I (LAD-I), requesting “limited additional” manufacturing information.
The company announced the rejection on Friday. The agency previously delayed its decision by three months, citing the need for more time to review the manufacturing process.
“While this regulatory update is a delay, we’re deeply committed to getting this treatment approved for the primary immunodeficiency community,” a Rocket spokesperson said in a statement. “We will continue our close collaboration with the FDA to complete its review expeditiously.”
LAD-I is an ultra-rare disease, and only a handful of children in the US will be diagnosed each year. The disease is caused by a mutation to a gene important for immune cell function.
With LAD-I, the immune system does not work properly, leading to serious infections. The only treatment is a stem cell transplant. Left untreated, few patients survive beyond infancy.
In clinical trials, nine patients received Rocket’s marnetegragene autotemcel, or marne-cel for short. All nine were alive one year following treatment, with the first patient alive four years after treatment.
To make the therapy, a patient’s blood stem cells are extracted and sent to a manufacturing facility, where they are then engineered with a lentiviral vector that carries a correct copy of the mutated gene. The cells are then sent back and infused into the patient after they receive chemotherapy to clear their bone marrow and make space for the new blood stem cells.
Donald Kohn“We think the stem cells are going to last forever, for a patient’s lifetime. And, therefore, hopefully, it is a cure,” Donald Kohn, a pediatric bone marrow transplant physician at UCLA who led the US clinical trial, told Endpoints News ahead of the FDA decision.
There are no approved gene therapies in the US for a primary immunodeficiency — a category of rare diseases including LAD-I in which the immune system fails to function properly.
In Europe, a gene therapy called Strimvelis was approved in 2016 for another severe immunodeficiency called ADA-SCID, though it’s not approved in the US. It’s been passed through several organizations — first GSK, then Orchard Therapeutics, and it is now owned by Fondazione Telethon, an Italian biomedical charity.
In the US, Orchard tried to develop a ADA-SCID gene therapy from UCLA’s Kohn, but abandoned it in 2021, citing the challenges of manufacturing a commercial-grade gene therapy. Orchard was bought by Kyowa Kirin earlier this year for $387 million — a fraction of the company’s one-time worth — further reflecting the obstacles associated with commercializing these rare disease gene therapies.
“It’s expensive to go from academic proof-of-principle to commercialization,” Kohn said. “To me, it seems like the manufacturing is the main block.”
He and other researchers have been looking for ways to bring cell and gene therapies developed for a range of pediatric rare diseases to market, including the ADA-SCID therapy, which investors don’t see as attractive opportunities because they may not have high returns, if any.
Rocket’s shares $RCKT fell 12% on Friday morning.