Trofinetide

A Neurogene gene therapy in development for the rare neurodevelopmental disorder Rett syndrome has encouraging early data in a small group of patients, an interim readout that comes a week after a private placement infused the biotech with $200 million to last it the next two years. But investors are focusing on a late-breaking development — a complication experienced by a patient who received the high dose of the experimental one-time treatment. The data reported after Monday’s market close are from seven total pediatric Rett syndrome patients treated with the Neurogene therapy, NGN-401. As of an Oct. 17 cutoff date, five patients had received the low dose and two received the high dose. For these patients, Neurogene said the therapy was safe and well tolerated. No treatment-related adverse events were reported. The adverse event happened in a third patient who received the high dose of NGN-401 after the data cutoff. Neurogene said it learned of the complication on Monday. The company said this complication was consistent with known risks of gene therapies delivered by adeno-associated viruses (AAV). NGN-401 uses the AAV9 viral vector for delivery. High doses of AAV are associated with inflammation and excessive activity of the complement system, a part of the immune system. The complication could keep Neurogene from pursuing development of the high dose of its gene therapy. The New York-based company’s stock price opened Tuesday at $48.28, down more than 32% from Monday’s closing price. Consumer / Employer Health Executives on Digital Transformation in Healthcare Hear executives from Quantum Health, Surescripts, EY, Clinical Architecture and Personify Health share their views on digital transformation in healthcare. By MedCity News In Rett syndrome, a mutation in one copy of the MECP2 gene leads to deficiency of a protein that’s important for normal brain function. The disease, which mainly affects girls, leads to delay in an infant’s early development. As the child gets older, the disease leads to a loss of the motor and communication skills that were attained. The lone FDA-approved Rett treatment is Acadia Pharmaceutical’s Daybue, a twice daily oral drug that reduces symptoms from the inherited disorder. The Neurogene therapy delivers to cells a full-length version of the MECP2 gene that is intended to replace the expression of the key protein, but not so much that the therapy causes complications. Neurogene accomplishes this with its EXACT transgene regulation technology, which acts as a “genetic thermostat” to control gene expression and void variability in expression that can lead to toxicity. In addition to the safety data reported for NGN-401, the early results also show some signs of efficacy in four of the patients in the low-dose group. According to measures taken with widely used psychiatric and Rett assessments, Neurogene reported a clinically meaningful gain of skills and developmental milestones compared to the natural history of the disease. William Blair analyst Sami Corwin, who spoke with Neurogene management, said the adverse event reported by the company appears to be a systemic inflammatory response that is a known side effect of high-dose AAV gene therapies. In a note sent to investors Tuesday, she said this complication can managed or resolved with corticosteroids or Soliris, an antibody drug designed to block a particular complement system protein. “Given the event does not appear to be CNS-localized, we do not think it is related to the [intracerebral ventricular] injection procedure or EXACT technology,” Corwin said. “Importantly, we do not see the event as impacting the continued development of the low dose.” Exclusive Heard at HLTH 2024: Insights from Innovative Healthcare Executives Executives from Imagine360, Verily, BrightInsight, Lantern, and Rhapsody shared their approaches to reducing healthcare costs and facilitating digital transformation. By MedCity News Leering Partners analyst Mani Foroohar said in a research note that the efficacy data were impressive enough even at the low dose to offer consistent differentiation compared to Rett natural history. Regardless of the adverse event, he expects the program will move into a pivotal study at least in the low dose. The low-dose cohort has a targeted enrollment of eight patients. In an investor presentation, Neurogene said it expects to complete enrollment in this group by the end of the year. In the first half of next year, the company will provide an update on the pivotal trial’s design. Additional Phase 1/2 data will be reported in the second half of 2025. Neurogene has also started enrolling an adolescent and adult group of patients, which it said could support expanding use of the drug to a broader swath of the Rett patient population. Neurogene’s competition in Rett includes Taysha Gene Therapies, which is in Phase 1/2 testing with TSHA-102. This gene therapy is made with a Taysha technology that mediates MECP2 expression. The company expects to report data from the first of two cohorts in the first half of 2025. Separately, Neurogene said it does not expect to proceed with its gene therapy for Batten disease. Given the rarity of this disease of the central nervous system, the company said it needs a streamlined regulatory pathway. Neurogene applied for a Regenerative Medicine Advanced Therapy (RMAT) designation for this program. Companies that receive this designation for a therapeutic candidate benefit from earlier and more frequent interactions with the agency and the possibility of an accelerated approval. The FDA turned down Neurogene’s RMAT application for its Batten program. Public domain image by Flickr user SciTechTrend