Acumen Pharmaceuticals, Inc. has announced that the first patient has been dosed with sabirnetug (ACU193) in the ALTITUDE-AD Phase 2 clinical trial designed to evaluate the clinical efficacy and safety of sabirnetug in patients with early AD.

“Today marks a significant milestone for Acumen and the Alzheimer’s community as we begin the Phase 2 trial of sabirnetug,” said Daniel O’Connell, Chief Executive Officer of Acumen.

“Sabirnetug is at the forefront of the next generation of Alzheimer's therapies, with encouraging Phase 1 results supporting its novel mechanism of action and selectivity for toxic amyloid beta oligomers. These results have led to a high level of investigator and patient interest in sabirnetug’s therapeutic potential and a strong start to the trial,” he added.

ALTITUDE-AD (NCT06335173) is a Phase 2, multi-center, randomized, double-blind, placebo-controlled clinical trial currently enrolling at sites in the United States and Canada, with plans for additional study centers in Europe and the UK. The study will enroll approximately 540 people with early AD who will be randomized to receive one of two dose levels of sabirnetug (35mg/kg or 50mg/kg once every four weeks) or placebo. Dose levels were determined to approach maximal target engagement based on modeling conducted from INTERCEPT-AD Phase 1 study results.

The primary endpoint will be change from baseline in the Integrated Alzheimer’s Disease Rating Scale (iADRS) at 18 months. Secondary endpoints will include the Clinical Dementia Rating – Sum of Boxes scale (CDR-SB), ADAS-Cog13, ADCS-ADL and various AD biomarkers. Standard safety measures and MRIs will also be assessed. Participants who complete the double-blind portion of the study will have the opportunity to continue into an open-label extension.

Sabirnetug is the first humanized monoclonal antibody to demonstrate in AD patients selective target engagement of AβOs, a soluble and highly toxic form of Aβ that accumulates early in AD and is a persistent trigger of synaptic dysfunction and neurodegeneration. Acumen is developing sabirnetug as a potential best-in-class antibody treatment for early AD.

Positive topline results from 62 participants in the Phase 1 INTERCEPT-AD trial (NCT04931459) showed sabirnetug to be well-tolerated with a favorable overall safety profile. The trial showed statistically significant, dose-related amyloid plaque reduction comparable to approved and late-stage amyloid-directed therapies at similar time points, low overall rates of ARIA-E, and evidence of target engagement that validated proof of mechanism. The results thus far support sabirnetug’s potential to offer differentiated safety and efficacy as a next-generation treatment for early AD.

Additionally, Acumen expects to initiate a Phase 1 bioavailability study to support a subcutaneous dosing option of sabirnetug in mid-2024, as announced in November 2023.