[Corrected 12:27 p.m. See below.] The FDA has rejected an experimental regenerative therapy that Enzyvant developed to restore immune system function in babies born with a rare disorder. The agency cited manufacturing issues, according to the company.
Enzyvant received the notification, formally known as a complete response letter, on Wednesday, CEO Rachelle Jacques tells Xconomy. That was the target date for a regulatory decision about the therapy, RVT-802. Jacques says Enzyvant’s application to the agency is still open, and the Cambridge, MA, company has 12 months to respond.
The next step is to meet with the FDA to discuss the letter. Jacques says the issues raised by the agency focus on how the therapy is made and there were no questions about the therapy’s safety or efficacy, nor is Enzyvant being asked to conduct additional clinical testing. But the Enzyvant therapy is among the first reviewed under a new regulatory pathway for regenerative medicines. Asked whether that had anything to do with the rejection, Jacques responded that she didn’t know.
“This is a novel therapy,” she says. “There’s not some well-recognized method of manufacturing a therapy like RVT-802. It is complex.”
The Enzyvant therapy was developed to treat a rare form of immunodeficiency caused by congenital athymia—being born without a thymus. The thymus is the organ where stem cells develop into T cells, the frontline defenders of the immune system. Without a properly functioning thymus, infants, unable to develop immunity, typically die by age 2.
Congenital athymia is exceptionally rare, occurring in 17 to 24 US births a year, according to company estimates. It can be caused by a rare genetic mutation, sometimes associated with a condition called complete DiGeorge anomaly. But developmental problems can also lead to babies being born without a thymus.
The Enzyvant therapy consists of transplanted thymus tissue that is taken (with parental consent) from babies undergoing cardiac surgeries. The donor tissue is screened for viruses or infectious diseases, and then processed to remove cells that were on their way to becoming T cells. Removing those cells reduces the risk of graft versus host disease, a condition in which immune cells from the donor attack the host. The therapy was initially developed at Duke University. Enzyvant licensed rights to the technology in 2017.
The processed thymus tissue is implanted into an infant’s leg, in the quadriceps, where it functions as the patient’s own thymus. Stem cells in the bloodstream find their way to the implanted tissue and then mature into functioning T cells. In time, patients build immunity. Enzyvant has reported that 76 percent of patients who received the treatment were still alive one year after treatment. [Paragraph updated with correct percentage figure.]
Without going into detail, Jacques says some of the questions raised by the FDA are ones that Enzyvant expected could be addressed after the therapy was approved. But she says she believes they can be resolved. Jacques adds that the FDA rejection does not affect the company’s plans to pursue approval in Europe, or to develop the therapy for other T cell disorders.
In the nearer term, Jacques says Enzyvant plans to work with Duke to figure out a way to ensure that patients who have congenital athymia can continue to receive the treatment. That will likely happen under a research program that Duke would have to establish, she says.
“This is a uniformly fatal condition,” Jacques says. “Speed is important here. We want to make sure there’s a path forward to be treated even if RVT-802 did not receive approval.”