Trontinemab

The FDA approved a new formulation of Eisai and Biogen’s Alzheimer’s drug Leqembi, an incremental step in the companies’ strategy to compete with Eli Lilly’s Kisunla. The new formulation can be injected under the skin, as opposed to being delivered by intravenous infusion — once a patient has completed 18 months of infusions. It will be branded as Leqembi Iqlik, and it comes with an auto-injector and a weekly dosing schedule, compared to biweekly treatment with the IV regimen. “The whole thing takes 15 seconds,” Eisai’s chief clinical officer Lynn Kramer said in an interview with Endpoints News before the decision. “It’s delivered once a week, and can replace the IV maintenance therapy.” In a statement, Eisai said Leqembi Iqlik will be priced at $375 per auto-injector, equating to $19,500 per year with weekly dosing. The annual cost of IV Leqembi is an estimated $26,632 during the 18-month initiation phase, though exact costs depended on a patient’s weight. When patients subsequently transition to monthly maintenance IV dosing, the annual cost is $13,316. Both Leqembi and Kisunla are the result of decades of research into amyloid plaque and its link to Alzheimer’s when it builds up in the brain. By clearing amyloid, the therapies have been shown to delay the hallmark cognitive symptoms of Alzheimer’s by several months when given to patients in early stages of the disease. But a key difference between the two is expected to shape treatment, as well as the market for the drugs. Leqembi is meant to be taken chronically — essentially, until a patient dies — whereas Lilly’s drug can be stopped once brain scans show that it has cleared amyloid. Kramer said he believes the differences between the drugs have created a “false discussion” about chronic versus temporary treatment, arguing that once plaque is removed, a lower-dose maintenance therapy is still needed because of the damage it does to the brain. Eisai and Biogen are hoping that the new formulation will make chronic dosing schedules more appealing for patients and their families. They’re also planning to file another application next week for subcutaneous dosing without the need for IV infusions beforehand. Kramer said they are expecting a priority review. “First you have to convince people they need chronic therapy. We believe they do,” Kramer said. “You don’t need the same dose after you remove the plaque. You need enough to suppress these biomarkers in this cellular injury.” In July, Eisai and Lilly both presented new long-term data at the Alzheimer’s Association International Conference claiming to show the advantages of their different approaches. However, questions remain about whether continuous treatment can help patients even after amyloid plaques are cleared, most notably if the plaques will come back once patients stop treatment. The FDA also announced Thursday that it will require an extra MRI for patients taking Leqembi after their third infusion to allow for extra monitoring of ARIA-E events. Previously, MRIs were only required before the fifth, seventh and 14th infusions. And the drugs will have to contend with other products in development. Roche is moving its experimental program trontinemab into Phase 3 studies, which are expected to launch later this year. In an earlier, Phase 1b/2a trial, 91% of patients taking trontinemab became “amyloid negative” after just 28 weeks of treatment.