INTERCEPT-AD trial of ACU193 for early Alzheimer’s ends enrollment

Top-line results are expected in the third quarter of this year

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The Phase 1 INTERCEPT-AD trial testing the investigational antibody ACU193 in patients with early Alzheimer’s disease has now completed enrollment, according to its developer, Acumen Pharmaceuticals.

Top-line results, including safety and proof-of-concept mechanism data, are expected ahead of schedule in the third quarter of this year.

“Today’s announcement marks an important milestone for Acumen and the Alzheimer’s community as we continue to explore ACU193 as a potential therapeutic option for people with early Alzheimer’s disease,” said Daniel O’Connell, president and CEO of Acumen, in a press release.

The buildup of the amyloid-beta protein in nerve cells has long been considered a key driver of nerve cell dysfunction and degeneration in Alzheimer’s.

It exists in three forms: monomers, oligomers, and plaques. Monomers contain a single amyloid-beta molecule, while oligomers contain a few molecules bonded together. Plaques are formed when large amounts of an insoluble form of amyloid-beta clump together.

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Monomers and insoluble plaques have been the main focus of amyloid-targeted therapies for Alzheimer’s over the last decade. But, research suggests the less prevalent oligomers may actually be the most toxic form of the protein, according to Acumen.

These soluble proteins stick together at the junction where nerve cells communicate with one another (synapses), blocking their communication. This is thought to be an early trigger for nerve cell degeneration.

ACU193 is an antibody designed to selectively bind and target these soluble oligomers. It’s unique in its selective targeting of this form of amyloid-beta form, whereas other anti-amyloid antibodies are less selective or target different types of amyloid-beta, according to the company.

Acumen believes by eliminating amyloid-beta oligomers, the treatment may slow disease progression and potentially lead to cognitive improvements for patients.

The treatment is designed to pose a low risk of amyloid-related imaging abnormalities (ARIAs) indicative of brain swelling or bleeding, which have been associated with other amyloid-targeted treatments.

“ACU193 builds on decades of scientific evidence that points to the role of soluble amyloid beta oligomers as primary and persistent toxins in Alzheimer’s pathology,” O’Connell said. “By targeting toxic oligomers, we hope to expand the understanding of targets beyond deposited amyloid plaques which we believe could provide patients with safer and more effective treatment options.”

INTERCEPT-AD (NCT04931459) enrolled 65 adults, ages 55-90, with mild cognitive impairment due to Alzheimer’s or mild Alzheimer’s dementia at 17 U.S. sites. It began dosing participants in October 2o21.

Its main goal is to evaluate the safety of single or multiple escalating doses of ACU193, delivered as an into-the-vein infusion. Participants will receive one to three doses of ACU193, or a placebo, and be monitored for up to about six months for side effects or safety-related events.

The treatment’s pharmacokinetics ( movement into, through, and out of the body) and proof-of-concept pharmacodynamics, that is, its ability to target amyloid-beta oligomers, will also be evaluated.

ACU193 was granted fast-track status by the U.S. Food and Drug Administration last year for treating early Alzheimer’s. A fast track designation offers financial incentives and regulatory support to speed the development of new treatments for serious diseases.