FDA Accepts NDA for Lecanemab Subcutaneous Autoinjector, RAP-219 Shows Promise in Early Trials, Blarcamesine Treatment Effects Observed at 3 Years

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a new announcement, the FDA has accepted Eisai’s biologics license application (BLA) for lecanemab-irmb (Leqembi) subcutaneous autoinjector (SC-AI) for weekly maintenance dosing in patients with early-stage Alzheimer disease (AD). The agency has set a PDUFA action date for August 31, 2025, for a decision to be made. If approved by the FDA, lecanemab would become the first AD treatment available for at-home subcutaneous administration using an autoinjector, with injections averaging 15 seconds. Following the biweekly intravenous (IV) initiation phase, patients would transition to weekly 360 mg subcutaneous maintenance doses to sustain clinical and biomarker benefits. Lecanemab, which received traditional approval in July 2023, was originally approved in a 100 mg/mL injection for patients with mild cognitive impairment (MCI) or mild dementia stage of the disease, the population in which treatment was initiated in clinical trials.

New data from the phase 1 PET and MAD-2 trials of RAP-219, a therapeutic in development for focal epilepsy, showed that treatment with the agent was generally well tolerated, with target exposures and receptor occupancy (RO) achieved within 5 days of dosing. These data, along with other phase 1 studies conducted to date, further support the therapy’s development in an ongoing phase 2a study that’s expected to have topline results released midway through this year. The PET trial (RAP-219-103) and MAD-2 trial (RAP-219-104) were complementary studies in healthy volunteers investigating RAP-219. The PET trial, an open-label study, confirmed neuroanatomical expression of TARPγ8 and explored the relationship between pharmacokinetics (PK) and brain target RO. It included three dosing cohorts, with one mirroring the ongoing Phase 2a epilepsy trial (0.75 mg daily for 5 days, then 1.25 mg daily for 9 days) and others using lower doses to characterize the PK-RO relationship.

Newly announced data from an open-label extension (OLE) of the phase 2/3 AD-004 trial showed that treatment with investigational blarcamesine (Anavex Life Sciences) resulted in continued treatment benefits through up to 4 years in patients with early-stage Alzheimer disease (AD). In addition, a delayed-start analysis of treatment with oral blarcamesine was significant reflecting importance of early treatment initiation. Results from the delayed-start analysis revealed a significant difference on Alzheimer’s Disease Assessment Scale-Cognitive Subcale-13 (ADAS-Cog13) between those who started blarcamesine treatment early and late (least square [LS] mean difference, –2.70; P = .0348) after 144 weeks, favoring the early start group. Notably, the treatment difference with blarcamesine continued to increase up to Week 192 (LS mean difference -3.83, P = 0.0165), suggesting that earlier initiation of treatment led to greater cognitive stability compared to delayed initiation by ~1 year.

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