Just over two months ago, a Swiss biotech claimed an Alzheimer's drug it invented was the first of its type to slow the cognitive decline associated with the disease. Detailed results, presented Thursday at a medical conference, show the company's seeming success isn't at all certain, however.
The drug, developed by AC Immune and licensed to Roche, reduced the rate of cognitive decline by 44% over placebo in a small Phase 2 study of some 270 patients with mild-to-moderate Alzheimer's. That finding, when it was disclosed in August, propelled shares in AC Immune higher by more than half on hopes it represented an advance for drugs that target an Alzheimer's-linked protein called tau.
But on Wednesday, Roche trial researcher Cecilia Monteiro told attendees of the virtual Clinical Trials in Alzheimer's Disease conference that patients who received AC Immune and the Swiss pharma's drug only benefited on measures of memory. On language and movement skills, treated study participants performed no better than those who received placebo.
Moreover, the drug, called semorinemab, didn't appear to help patients when tested on other measures of cognition and function. Notably, when researchers scanned patients' brains using a technique called positron emission tomography, they observed no significant reduction in tau levels, raising questions about how well the drug does what it was designed to do.
Even mixed results, however, are uncommon in studies of Alzheimer's drugs, almost all of which have failed outright. AC Immune's results are also notable for research into blocking tau, an approach to treating the disease that drugmakers have turned to over the past decade as the dominant hypothesis of targeting a protein called amyloid beta sputtered.
"We're always happy to see positive clinical data. It doesn't come very often in our field," Stephen Salloway, a Brown University neurology professor, said in his commentary on the semorinemab data following the CTAD presentation.
Targeting amyloid, however, is newly resurgent after the Food and Drug Administration's controversial approval of Biogen's Aduhelm, a decision that recently spurred Eisai and Eli Lilly to submit their similar acting therapies for accelerated review.
Drugs blocking tau, meanwhile, have hit several setbacks, as AbbVie, Biogen and Lilly have each stopped work on various candidates this year.
Lilly scrapped one tau-targeting drug, called zagotenemab, after it failed a Phase 2 trial, for instance. The result led the company's top scientist, Dan Skovronsky, to doubt whether antibody drugs like zagotenemab or semorinemab could have any effect on tau buildup.
"I would be reluctant to invest in really any anti-tau antibody, given what we've seen here," Skovronsky said in Lilly's latest earnings call.
The company is working on a small molecule alternatives instead, he said.
Roche and AC Immune, meanwhile, haven't specified what their next steps for semorinemab are. Patients in the Phase 2 trial have the option to participate in an extension study, though which all will receive the drug. Those results will be critical to the drug's future as AC Immune CEO Andrea Pfeifer said the companies want to review data from that trial before deciding whether to start a Phase 3 study.
"We really need to understand the biomarkers. We really want to see, if after longer treatment, you see functional improvements," she said in an interview, before a decision can be made.
The company's shares fell 21% after the data were released.