Acumen Pharmaceuticals plans to conduct a Phase II or Phase II/III clinical trial investigating the monoclonal antibody ACU193 in patients with early Alzheimer’s disease (AD), says president and CEO Daniel O’Connell. The company expects to initiate the next phase trial in 2024.
In February, Acumen completed the enrolment for a Phase I trial investigating ACU193. It is a randomised, placebo-controlled trial with 65 patients enrolled into single-ascending dose (SAD) and multiple-ascending dose (MAD) cohorts. The company plans to read out the topline results in Q3 2023.
ACU193 is a humanised monoclonal antibody (mAb) that was developed based on its selectivity for soluble amyloid beta oligomers (AβOs), according to the company’s website.
Plans for the next stage
The information about the pharmacokinetics, target engagement, and safety and tolerability profiles will guide Acumen on whether to initiate a Phase II or a Phase II/III trial, O’Connell says. The CEO adds that Eli Lilly’s and Eisai’s clinical trials in AD might stand as exemplary design models. Clinical Trials Arena previously compared the two trials investigating donanemab and lecanemab.
If it was a conventional Phase II trial, it would explore dose-ranging and aim to demonstrate clinical proof of concept. The Phase II trial would enrol around 300 patients, as seen in Eli Lilly’s Phase II trial (NCT03367403) investigating donanemab.
Alternatively, Acumen is considering a more expansive study that would start as a Phase II trial with the possibility to expand into Phase III and serve as a registrational study, at least in the US, with the FDA. If it was a Phase II/III study entailing an interim analysis justifying the expansion into the full registration study, it would probably have around 1,200–1,500 patients, O’Connell says. A similar number of patients was seen in Eisai’s Phase III trial (NCT03887455) investigating lecanemab.
Regarding endpoints, the next phase study will look at the disease modification and slowing of progression at 18 months. Acumen is also very interested in biomarker data, as the field is putting forward a lot of information on fluid biomarkers, particularly around phosphorylated tau and other synaptic biomarkers, O’Connell explains. “It is such a rapidly evolving space that we are continuously learning as we move forward,” he adds. Biomarker-based approaches are also being explored in other central nervous system (CNS) fields, such as amyotrophic lateral sclerosis (ALS).
Current AD trial landscape
For the AD space, 2022 was a chaotic year, with the controversial approval of Aduhelm and lack of sales still hanging over the field. However, there are major questions to answer in 2023, while others explore new approaches, such as vaccines.
According to GlobalData’s Clinical Trials Database, there are 282 industry-sponsored planned or ongoing clinical trials investigating drugs in AD. Half of these trials are in the early stages of development. GlobalData is the parent company of Clinical Trials Arena.