The drug failed to meet its primary efficacy endpoint, as well as two secondary endpoints.
AC Immune, based in Lausanne, Switzerland, and Genentech, a U.S.-based Roche company, announced topline results from the TAURIEL Phase II clinical trial of semorinemab in early Alzheimer’s disease. The drug failed to meet its primary efficacy endpoint, as well as two secondary endpoints.
Semorinemab is an anti-tau antibody. The primary efficacy endpoint was decreasing decline on the Clinical Dementia Rating-Sum of Boxes (CDR-SB) compared to placebo. The two secondary endpoints were Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog13) and Alzheimer’s Disease Cooperative Study Group – Activities of Daily Living Inventory (ADCS-ADL).
Genentech is continuing to analyze data and plans to present TAURIEL data at an upcoming scientific conference. Meanwhile, the second Phase II LAURIET trial in patients with moderate AD is ongoing.
“Today’s news is surprising and disappointing, given what we as a field know about Tau and its strong spatiotemporal correlation with both symptoms and pathology in AD,” said Andrea Pfeifer, chief executive officer of AC Immune. “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 (NDD). We would like to thank the patients, caregivers and investigators who participated in this important, ground-breaking trial and look forward to the final results from our partner, Genentech.”
The TAURIEL Phase II trial investigated semorinemab in a 73-week, double-blind, placebo-controlled study in prodromal to mild AD. It involved 457 patients across 97 study sites. The incidence of adverse events was about the same between the semorinemab and placebo arms.
TDP-43 and alpha-synuclein are major pathologies in neurodegenerative diseases and are thought to be important co-pathologies in Alzheimer’s.
Two abnormal proteins are associated with Alzheimer’s disease—amyloid and tau. In general, amyloid appears earlier in the disease while tau tends to appear later in the disease.
In addition to semorinemab, AC Immune has ACI-35.030, an anti-phospho-Tau vaccine, which is in Phase II studies; ACI-3024, a first-in-class small molecule that moves through cell membranes to inhibit intracellular Tau aggregates. They expect Phase I data from Eli Lilly sometime this year; and PI-2620, a Tau-PET tracer, which is being evaluated in a longitudinal Phase II trial in patients with AD and a Phase I study in progressive supranuclear palsy (PSP).
The company has nine therapeutic and three diagnostic product candidates, with six currently in clinical trials. In addition to collaborations with Genentech and Eli Lilly, it has a partnership with Janssen Pharmaceuticals, a Johnson & Johnson company.
“Our proprietary technology platforms and proven business model of discovery, early development and partnering high-risk therapeutic candidates for AD have successfully generated CHF 334 million in non-dilutive funding and enabled us to accelerate clinical development of our product candidates in collaboration with world-leading partners,” Pfeifer said. “This strategy enables us to focus our resources on advancing the next generation of first-in-class or best-in-class assets. With current funding through Q1 2024, this robust risk-and-financial-sharing strategy will continue unaffected as we work diligently to mature our proprietary candidates and generate substantial future value for the company.”
This marks yet another of a long line of failures in the Alzheimer’s space. Most have focused on clearing or preventing beta-amyloid. The only one that might be considered successful is Biogen’s aducanumab—but that will depend on if the U.S. Food and Drug Administration (FDA) approves it, which is currently under review. And that’s not without its own set of controversies. The company originally folded the trials after interim analyses suggested they would fail to meet their endpoints, but further analysis of a subset of patients at the highest dosage suggested efficacy, so Biogen submitted it to the agency in July 2020.
Tau has also had setbacks, including another failure by Biogen after a humanized monoclonal antibody targeting N-terminal tau failed a Phase II trial late in 2019.
TauRx’s hydromethylthionine mesylate, a tau aggregation inhibitor, did not show benefit over placebo when dosed with Aricept in a Phase III trial in 2016. TauRx began a new Phase II/III trial of the drug in 2018 with a lower dose with data expected in 2021 or 2022. AbbVie is testing ABBV-8E12 in Phase II—the drug binds to abnormal tau tangles. That drug failed a Phase II trial in PSP last year, but the Alzheimer’s work continues.
Roche also is working with UCB on another tau-targeting drug, UCB0107, designed to block or decrease the buildup of tau proteins. It is testing it in PSP, but will carry and fund a proof-of-concept study in Alzheimer’s, which if it succeeds, Roche will continue to develop.
