Neurogene, Inc. (New York)

Neurogene disclosed in a filing with the US Securities and Exchange Commission that a patient who suffered a serious adverse event (AE) in an ongoing Phase I/II study of its gene therapy for Rett syndrome has now died. The company first said last week that a participant given the higher 3E15 vg dose of NGN-401 had experienced a treatment-related serious AE described as "consistent with known risks of AAV gene therapy." The issue clouded promising efficacy seen in the low-dose group (for related analysis, see Spotlight On: SAE could swing balance of power in Rett gene therapy battle).More recently, Neurogene indicated that the participant — who was dosed on November 5 — was in a "critical condition" having experienced signs of a systemic hyperinflammatory syndrome, which are associated with aberrant cytokine release and include haemophagocytic lymphohistiocytosis and multisystem inflammatory syndrome. NGN-401 is an AAV9 gene therapy candidate that works by delivering a full-length human MeCP2 gene using Neurogene's EXACT transgene regulation technology. The biotech continues to investigate the lower 1E15 vg dose of NGN-401 in the trial in both the paediatric and adolescent/adult cohorts.

The clinical trial participant who was hospitalized for severe complications after receiving the high dose of Neurogene’s experimental Rett syndrome gene therapy has died. Neurogene disclosed the death in a regulatory filing after the market close Thursday. The company said the FDA is permitting the Phase 1/2 study to continue with the low dose of the therapy, code-named NGN-401. Neurogene added that it will incorporate this dose in planning the design of the clinical trial expected to support a regulatory submission seeking FDA approval of the gene therapy. Rett syndrome is a neurodevelopmental disorder stemming from a mutation in one copy of the MECP2 gene. Neurogene’s NGN-401 delivers to cells a functioning version of that gene with the goal of restoring expression of the key protein that’s important for brain function. The therapy reaches brain cells aboard an adeno-associated virus (AAV), a widely used delivery vehicle for genetic medicines. But these engineered viruses can trigger dangerous immune responses. presented by Market Trends to Watch for Health Systems and Their Specialty Pharmacies The future looks bright for the integrated specialty pharmacy model – for health systems, providers, and most importantly, for patients. By Jake Gaffey, MBA, Chief Strategy Officer at Shields Health Solutions Neurogene disclosed the patient complication last week, a late addition to an interim clinical trial update that showed the gene therapy was safe and well tolerated so far for five patients who received the low dose and two who received the high dose. The complication developed in a third patient in the high dose group who received that dose after the cutoff date for the interim update. Neurogene said the adverse effect was consistent with the known immune response risk associated with high doses of AAV. In a Monday update, Neurogene said the patient was in critical condition. Neurogene is conducting the NGN-401 clinical trial under Support for clinical Trials Advancing Rare disease Therapeutics (START), an FDA pilot program designed to accelerate the development of new therapies for rare diseases. Companies whose experimental treatments are selected for this program benefit from more frequent advice and communication with the agency. Neurogene is one of seven companies participating in START. Neurogene said after it learned of the serious adverse event, it “proactively engaged with the FDA under the START program.” The company said the regulator completed a review of the safety data and then allowed the study to proceed in the low-dose group. Use of the high dose was paused, and Neurogene said it does not plan to enroll more patients at that dose level. In a Tuesday research note sent to investors regarding Neurogene’s third quarter 2024 financial results, William Blair analyst Sami Corwin wrote that that she does not see the adverse event affecting Neurogene’s ability to develop the low dose of NGN-401, which showed an “impressive efficacy and tolerable safety profile.” She added that the adverse event and the subsequent FDA interactions underscore the advantages of the START program. Corwin said the agency was able to swiftly review the safety data, which likely prevented imposition of a clinical hold — traditionally the FDA’s only recourse while it investigated severe safety events in gene therapy studies. 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 “We continue to see NGN-401’s selection for the highly competitive and innovative START program as potentially accelerating the clinical development of NGN-401 and the decision to discontinue the development of the high-dose could speed up discussions regarding NGN-401’s regulatory pathway, as the company no longer has to wait to collect efficacy data from the high-dose cohort,” Corwin said. Neurogene previously said it expected to complete enrollment of the low-dose group by the end of this year. In its quarterly report, the company said the timeline has changed because of the need to update the clinical trial protocol to remove the high dose. Neurogene said it expects to resume dosing in the low-dose cohort once those revisions are complete. The company reiterated that it plans to provide an update on the design of NGN-401’s registrational study in the first half of next year; additional interim Phase 1/2 data are expected in the second half of 2025.

Today, a brief rundown of news involving Halozyme and Neurogene, as well as updates from Argenx and Kura Oncology that you may have missed.Halozyme Therapeutics on Friday said it withdrew an offer to buy Evotec after the German drug discovery and contracting company refused to engage in acquisition talks. Halozyme sought to buy Evotec in a deal valuing the firm at 2 billion euros, or about $2.1 billion and, in the months leading up to its proposal, sought to discuss the idea with multiple members of Evotec leadership. But several meeting requests were rejected and it is now become evident that there is no interest in a deal, Halozyme CEO Helen Torley said in a statement. Private equity firm Triton has also shown interest in Evotec, however. It recently acquired a 10% stake and is reportedly exploring a possible buyout. Ben FidlerA study participant who received a gene therapy Neurogene is developing for Rett syndrome has died, the company revealed in a regulatory filing Thursday. Neurogene shared last week that the patient, who was given a high dose of the therapy on Nov. 5, was in critical condition after experiencing a side effect consistent with known risks of gene therapies delivered with an adeno-associated virus, or AAV. On Thursday, Neurogene disclosed the patient has since died from complications of that side effect, a rare and life-threatening hyperinflammatory syndrome associated with high systemic exposure to AAV. The Food and Drug Administration recently allowed Neurogene to continue testing with a lower dose. Ben FidlerArgenx is moving ahead with plans to test its drug efgartigimod in several subtypes of myositis, a group of rare autoimmune diseases that affect a range of organs and muscles. The decision to green light further testing followed Argenxs receipt of efficacy and safety results from the Phase 2 portion of a Phase 2/3 study its been conducting. Treatment with efgartigimod, which Argenx sells as Vyvgart for myasthenia gravis and other rare disorders, led to significant patient improvement compared to placebo in the Phase 2 study, the company said Nov. 20. The news, which lifted Argenx stock, provides another market opportunity for efgartigimod that analysts think could be worth at least $1 billion in peak annual sales. Ned PagliaruloKyowa Kirin is paying Kura Oncology $330 million upfront for rights to an experimental oral leukemia drug now in Phase 1 testing, Kura said Wednesday. Under the terms of the deal, Kura could receive up to $420 million more should ziftomenib reach market for relapsed or treatment-resistant acute myeloid leukemia expressing a mutation called NPM1. The deal also gives Kyowa Kirin opt-in rights to ziftomenib in solid tumors. Kura will lead development and book sales in the U.S. that will be shared with Kyowa Kirin, while Kyowa Kirin will handle those responsibilities outside the U.S. Ziftomenib is a new type of cancer drug that blocks a protein called menin, which when it interacts with a second protein helps diseased leukemia cells survive and reproduce. Jonathan GardnerDouglas Throckmorton, the deputy center director for regulatory programs at the Food and Drug Administration, plans to retire in January after 27 years at the agencys main drugs office. Hes been in his current role, which oversees a wide range of issues, since 2005. In an email to FDA staff, Patrizia Cavazzoni, the director of the agencys Center for Drug Evaluation and Research, said Throckmorton has had an immeasurable impact on public health. Throckmorton first informed Cavazzoni in September of his plans to retire. Ned Pagliarulo '