Acumen's stock surges as early Alzheimer's data suggest next-gen Leqembi rival is active

Acumen Pharmaceuticals has early clinical evidence that its Alzheimer’s disease candidate safely reduces amyloid plaque. But while the readout partly addresses concerns about the molecule’s activity, it leaves room to question whether the candidate is sufficiently differentiated from more advanced products.  

Virginia-based Acumen designed its antibody to target different species of amyloid beta than drugs such as Biogen and Eisai’s Leqembi in a bid to improve efficacy while reducing the rate of amyloid-related imaging abnormalities with edema (ARIA-E). Leqembi targets protofibrils, a soluble form of amyloid beta, and insoluble forms of the protein. The mechanism works well enough for the drug to secure FDA approval but also landed the product with a black box warning for ARIA.

Acumen’s candidate, ACU193, targets amyloid beta oligomers, differentiating it from Leqembi. Going into the phase 1 readout, it was unclear whether the antibody would engage the target and clear amyloid plaques. The data presented at the Alzheimer’s Association International Conference 2023 on Sunday resolve that uncertainty.

At higher doses, ACU193 caused similar levels of plaque reduction to Leqembi. The number of patients is small—Acumen treated 16 patients across the two dose cohorts it highlighted—and the company is yet to track enough people for long enough to show the durability of the effect or reveal whether it translates into improved cognition. But the efficacy signal was sufficient to encourage Acumen to plan a phase 2/3 trial.

If, as appears plausible based on the very limited data, ACU193 is no better than Leqembi at improving cognition, Acumen will need to find other ways to differentiate its product to overcome the multiyear head start it has ceded to its rivals. Safety and tolerability offer Acumen an opportunity to stand out. 

Yet, the phase 1 data fail to convincingly show that ACU193 can seize that opportunity. Across the 48 patients in the safety data set, Acumen reported a 10.4% rate of ARIA-E. The rate in the 14 patients who received 60 mg/kg, the highest dose, was 21.4%. The rate of symptomatic ARIA-E was lower, with one patient in the whole study, who was in the 60-mg/kg cohort, developing the adverse event.

Acumen highlighted the fact that no APOE4 homozygote patients exhibited ARIA-E. The Leqembi label (PDF) warns that APOE4 homozygote patients have a higher incidence of ARIA when treated with the Eisai-Biogen drug. The lack of any ARIA-E cases in the subpopulation in the Acumen trial is positive but, with the biotech only having data on six patients, could be a fluke that vanishes in larger data sets.

The next step is to generate larger data sets. Buoyed by the data, which initially sent its share price up 44% to $9.03 in premarket trading Monday, Acumen plans to talk to regulators and determine a timeline for moving into a phase 2/3 study.