Swiss biotech AC Immune and partner Genentech have announced that their candidate semorinemab is the first tau-targeting monoclonal antibody to show evidence of clinical activity in Alzheimer’s disease.
Top-line data from the phase 2 Lauriet trial showed that the drug met one of its co-primary endpoints, reducing cognitive decline by 43.6% from baseline compared to placebo in people with mild to moderate Alzheimer’s disease.
However, the drug did not meet its second co-primary endpoint (reducing the rate of functional decline from baseline) or two secondary efficacy endpoints. Safety data showed that semorinemab is well tolerated with an acceptable safety profile.
“The top-line results of the Lauriet phase 2 clinical trial of semorinemab are remarkable in that it is the first time we have seen a therapeutic effect by a monoclonal anti-tau antibody therapy,” said Andrea Pfeifer, CEO of AC Immune. “We also are excited by the fact that this is the first time a monoclonal antibody has had a therapeutic impact on cognition in the mild-to-moderate Alzheimer’s disease patient population.”
Pfeifer said they were “still cautious about what this may mean for patients”, pointing to the lack of effect on the rate of functional decline. “Alzheimer’s disease is a slow-moving chronic disease and this small trial was relatively short, 49 weeks; so, the data from the open-label extension may be important in elucidating the potential of semorinemab in this patient population.”
While the data is “encouraging for therapeutic strategies targeting tau”, she said they looked forward to additional data from the company’s other clinical-stage tau programmes, which include vaccine ACI-35, partnered with Janssen, and small molecule morphomer tau aggregation inhibitor, partnered with Eli Lilly.
AC Immune shares rose more than 75% on the announcement, marking a “surprising” turnaround for the programme for Jefferies analyst Lucy Codrington. Writing to investors, she said AC Immune’s data was particularly unexpected after a previously failed trial last September looking at cognition and function in patients with earlier stages of Alzheimer’s.
Rachelle Doody, global head of neurodegeneration at partner Roche, agreed that the data represented a positive step forward. “Although we are encouraged by the positive outcome for one co-primary endpoint measuring cognitive performance, we will continue our analyses of this data and continue the open label portion of the study to better understand why semorinemab didn’t show an effect on the co-primary endpoint measuring functional decline in activities of daily living, or on the secondary endpoints,” she said.