Acumen Pharmaceuticals recently unveiled early clinical evidence showcasing the potential of its Alzheimer’s disease candidate in safely reducing amyloid plaque. While this development partially addresses concerns regarding the molecule’s activity, it also raises questions about its differentiation from more advanced products in the market. Located in Virginia, Acumen took a distinct approach by designing its antibody to target different species of amyloid beta compared to drugs like Biogen and Eisai’s Leqembi. By focusing on enhancing efficacy and reducing the occurrence of amyloid-related imaging abnormalities with edema (ARIA-E), Acumen aimed to carve out a unique position for its candidate.
Leqembi primarily targets protofibrils, a soluble form of amyloid-beta, as well as insoluble forms of the protein. Although this mechanism secured FDA approval for the drug, it also led to the inclusion of a black box warning for ARIA. In contrast, Acumen’s candidate, ACU193, specifically targets amyloid-beta oligomers, setting it apart from Leqembi in terms of its therapeutic approach. Prior to the phase 1 readout, it remained uncertain whether ACU193 could effectively engage the target and clear amyloid plaques. However, the data presented at the Alzheimer’s Association International Conference 2023 helped clarify this uncertainty.
The preliminary findings revealed that ACU193, at higher doses, demonstrated similar levels of plaque reduction compared to Leqembi. It’s important to note that the patient sample size was relatively small, as Acumen treated a total of 16 patients across the two highlighted dose cohorts. Furthermore, the company has not yet tracked patients for a sufficient duration to determine the durability of the effect or establish whether it translates into improved cognition. Nevertheless, the encouraging efficacy signal prompted Acumen to lay out plans for a phase 2/3 trial, seeking to further evaluate and validate the candidate’s potential.
In the event that ACU193 proves to be on par with Leqembi in terms of cognitive improvement, Acumen will need to find alternative ways to differentiate its product from competitors who have enjoyed a multi-year headstart. One potential avenue lies in focusing on safety and tolerability, providing Acumen with an opportunity to stand out in the market. However, the phase 1 data does not unequivocally demonstrate ACU193’s ability to seize this opportunity.
Based on the safety dataset comprising 48 patients, Acumen reported an ARIA-E rate of 10.4%. For the 14 patients who received the highest dose of 60 mg/kg, the rate increased to 21.4%. However, the rate of symptomatic ARIA-E remained relatively low, with only one patient from the entire study, belonging to the 60 mg/kg cohort, experiencing this adverse event. Acumen emphasized the absence of ARIA-E cases among APOE4 homozygote patients, which contrasts with Leqembi’s label that highlights a higher incidence of ARIA in this particular patient subgroup. Nevertheless, it’s worth noting that Acumen’s data on ARIA-E in this subgroup is based on a limited sample size of only six patients, and further investigation is required to confirm these findings in larger datasets.
Acumen aims to generate more extensive datasets to gather additional evidence and insights regarding ACU193’s potential. The positive initial data, which led to a remarkable 44% surge in the company’s share price during premarket trading, has emboldened Acumen to engage with regulators. Through discussions with regulatory authorities, Acumen aims to determine a timeline for advancing into a phase 2/3 study, thereby progressing further in the development of their promising Alzheimer’s disease candidate.