Neurogene, Inc.

The FDA has allowed Neurogene to keep studying the low dose of its Rett syndrome gene therapy candidate in both trial cohorts.\n A patient has died after receiving the high dose of Neurogene’s Rett syndrome gene therapy candidate. The biotech had disclosed the adverse event Nov. 11, and explained the patient was in critical condition Nov. 18. Thursday, Neurogene provided an update on the individual in a financial regulatory filing. The company said the person died “following complications from a rare and life-threatening hyperinflammatory syndrome associated with systemic exposure to high doses of adeno-associated virus (AAV).”The earlier updates established that the patient had received the gene therapy, dubbed NGN-401, Nov. 5 and subsequently showed signs of systemic hyperinflammatory syndrome.Some people develop the syndrome after receiving high doses of AAV, the vector used to deliver many gene therapies. The Rett patient was the third person to receive the high dose of NGN-401. Neurogene\'s chief financial officer Christine Mikail had discussed the impact of dosing Nov. 11, telling analysts the adverse event was “not somewhat surprising as a result of the 3x difference in the dose.”   In yesterday\'s filing, Neurogene explained that the FDA has allowed the biotech to continue studying the low dose in both cohorts, one of which is enrolling children. The other cohort is enrolling adolescents and adults. Neurogene will incorporate the low dose into the planning for the design of its registrational trial, according to the Nov. 21 filing. Mikail had expressed confidence in the low-dose data earlier this month.“We\'re pretty excited about what we\'re seeing in the low dose, both from an efficacy and safety perspective and have collected a significant amount of information to help inform what the pivotal design could look like,” the CFO said. “The low dose data is strong enough to go to the agency with and that\'s really where we collected the most data to date.”

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.

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 '