Tau-Targeting Alzheimer’s Drug from AC Immune, Roche Fails in Phase 2

An Alzheimer’s disease drug from partners AC Immune and Roche has failed a mid-stage clinical trial, adding another compound to the list of experimental therapies that have fallen short of demonstrating that they can treat the neurodegenerative disorder.

The drug, semorinemab, was tested in patients with early Alzheimer’s disease. It did not achieve the Phase 2 study’s main goal of beating a placebo in slowing decline according to a dementia scale, AC Immune (NASDAQ: [[ticker:ACIU]]) reported Wednesday. The company added that the drug also failed to beat a placebo in secondary goals of showing improvement in cognitive symptoms and the ability to perform the activities of daily living.

Genentech is still analyzing the results and plans to present them at an upcoming medical conference. A second Phase 2 study testing the drug in patients with moderate Alzheimer’s is ongoing.

Shares of Lausanne, Switzerland-based AC Immune opened Wednesday at $5.15 per share, down more than 40 percent from Tuesday’s closing price.

Semorinemab is an antibody designed to target the buildup of tau on the outside of cells. Tau is one of the brain proteins whose accumulation is associated with the progression of Alzheimer’s. The drug was evaluated in double-blinded Phase 2 study that compared the drug against a placebo. A total of 457 patients enrolled in the 73-week clinical trial. No safety problems were reported in connection with the drug.

In a prepared statement, AC Immune CEO Andrea Pfeifer said the results were “surprising and disappointing,” given what the Alzheimer’s field knows about tau and the correlation of the protein buildup to the symptoms and progression of the disease. “We believe the full data analysis of this first-of-its-kind study will yield information about this promising target that will advance our understanding and inform future efforts to successfully develop effective therapeutics for neurodegenerative diseases,” she added.

SVB Leerink analyst Marc Goodman wrote in a note to investors that the results are disappointing to the company and to the Alzheimer’s community, as the study was hoped to validate the anti-tau antibody approach to treating the disease. He added it’s too soon to tell why the clinical trial failed. If the drug was able to engage its target, the study might still support the tau hypothesis despite the Phase 2 failure, Goodman said.

AC Immune’s pipeline includes ACI-35.030, an anti-tau vaccine that generates an antibody that can bind to multiple sites on an antigen—sites different than the one targeted by semorinemab. This vaccine is currently in Phase 2 testing under a partnership with Johnson & Johnson subsidiary Janssen Pharmaceuticals. The company has reached Phase 1 testing with ACI-3024, a small molecule designed to pass through the cellular membrane to block aggregation of tau inside a cell. That drug candidate, in development under a partnership with Eli Lilly (NYSE: [[ticker:LLY]]), is expected to report data later this year. AC Immune says it expects its cash reserves are enough to support the company through the first quarter of 2024.

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