After failing to receive the RMAT designation from the FDA for its early-stage Batten disease gene therapy, Neurogene tells investors that it’s evaluating options for the program.
In addition to a Monday morning announcement of a complication for its Rett syndrome gene therapy, Neurogene has dropped another doozy on investors in stopping its gene therapy program for Batten disease.
In its third quarter earnings release and a prior press release on Nov. 11, Neurogene stated that while it had completed enrollment for the NGN-101 Phase I/II trial, it does not expect to move forward at this time. Due to the rarity of CLN5 Batten disease—estimated to occur in 2 to 4 of every 100,000 births in the U.S.—the biotech was counting on the FDA’s Regenerative Medicine Advance Therapy designation to support the program. However, the RMAT application was denied, and the company is now “evaluating options for the program.”
This blow follows on the heels of a hit to another of its lead rare disease programs, NGN-401 for Rett syndrome. Neurogene shared news of a serious adverse event last Monday, sending shares tumbling 35%. This Monday, the company revealed further details including that the patient remains in critical condition, sending the stock down another 36% upon the opening bell—though William Blair analyst Sami Corwin said in a note to investors Tuesday that this negative stock reaction was “overblown.”
Indeed, the adverse event reported was not fatal to the Rett program. Neurogene stated that the patient suffering from systemic hyperinflammatory syndrome, a dangerous immune response associated with high doses of adeno-associated virus gene therapies, was in the high-dose arm of the trial, which will now be paused, and no further patients will be enrolled in the cohort. The low-dose arm will continue, however. No other serious adverse events have been reported in the trial.
The first four patients treated at the lower dose showed consistent improvements across key Rett syndrome scales, and all five achieved a clinically meaningful rating of “much improved” on the clinical global impression-improvement scale, the company said. Treatment-related adverse events in this dosage group were grade 1, with the treatment well-tolerated.
NGN-401 is part of the FDA’s START program for supporting and accelerating clinical development for rare diseases. Within this program, Neurogene was able to quickly get an FDA review of the safety data for NGN-401 and be allowed to proceed with the Phase I/II trial at the lower dose.
Corwin credits the START program with likely preventing a clinical hold. She continues to see the efficacy data as “impressive” and reiterated the investment firm’s view that NGN-401 is a “potentially first-in-class and best-in-class gene therapy for Rett syndrome.”
In its third quarter release, Neurogene said it will share its registrational trial design for NGN-401 in the first half of 2025. Thanks to a private placement of $200 million earlier this month, the company’s cash runway currently extends into 2027. Neurogene expects to advance another product candidate into the clinic next year.
Correction (Nov. 19): This story was updated to clarify that Neurogene first announced the Batten disease discontinuation on Nov. 11 prior to releasing details on the adverse event in a study of Rett syndrome, not after. BioSpace regrets the error.
