Eisai and Alzheon presented new data in March at the AD/PD annual meeting in Copenhagen, focusing on Alzheimer’s disease treatments for individuals with two copies of the APOE ɛ4 gene variant. This genetic profile is known to increase both the risk of developing Alzheimer’s and experiencing brain bleed events, called ARIA-H and ARIA-E, during treatment with certain therapies such as Leqembi.
The research is significant because some regulators have restricted access to anti-amyloid therapies for APOE ɛ4 homozygotes due to safety concerns. Eisai's real-world analysis showed that these treatment-associated bleeds were less common than previously observed in clinical trials, especially after six months of therapy. Additionally, most patients did not experience disease progression during the study period.
Aaron Burstein, head of search and evaluation at the Alzheimer’s Drug Discovery Foundation, said to BioSpace: “The conference had a significant focus on biomarkers, and there [have] been such tremendous advances that these biomarkers are really allowing us to understand the underlying biology of the patients that we’re trying to treat with therapies.” He described Eisai’s data as “very encouraging” and said it “provides additional support for the potential use of these agents in the APOE4 carrier status as was approved by FDA.”
Alzheon also shared updated results from its Phase 3 trial involving valiltramiprosate in people homozygous for APOE4. While topline results missed their primary endpoint last year, new biomarker and imaging data presented this year indicated positive effects among patients who began treatment with mild cognitive impairment rather than more advanced disease. Burstein said regarding Alzheon’s findings: "the biomarker data provided support that the hypothesized clinical benefits they were seeing were associated with measures consistent with actually having effects on the underlying biological processes.”
Lynn Kramer, chief clinical officer at Eisai, explained that real-world analysis involving 207 U.S. patients found a lower incidence of ARIA among APOE4 homozygotes compared to earlier trials—21.2% versus 13.7% for noncarriers—with nearly all cases being asymptomatic. He noted: “Our thinking is they should be treated earlier like everybody else if you want to get maximum benefit... But I think this type of information makes physicians maybe more comfortable in understanding the risks so that they start treating the patients a little sooner.”
John Hey, chief scientific officer at Alzheon, emphasized their drug development strategy focused on high-risk groups due to unmet needs stemming from restrictions around Leqembi use. He highlighted sustained reductions in p-tau-217 levels—a key biomarker—in Phase 2 studies over four years among mild cognitive impairment participants.
Both companies plan further studies targeting early-stage or genetically high-risk populations with hopes for expanded therapeutic options and improved outcomes.
