February 28, 2017
By Alex Keown, BioSpace.com Breaking News Staff
LAUSANNE, Switzerland – As investors, patients and family members cling to the hope for an effective Alzheimer’s disease therapy, eyes are turning to Genentech as the company initiates a second phase III clinical trial of the Alzheimer’s therapy crenezumab, an anti-Abeta antibody.
The trial is expected to recruit 750 patients with prodromal or mild Alzheimer’s disease. It is expected to be complementary to the current Phase III CREAD1 trial of 750 participants with prodromal or mild Alzheimer’s disease, expected to read out in 2020.
Crenezumab was initially discovered by Swiss-based AC Immune using its SupraAntigen technology platform. Genentech licensed the drug in 2006. AC Immune said it is not expecting to receive any milestone payments from the start of this second Phase III trial.
Developing an effective therapy for Alzheimer’s disease has been an incredibly difficult goal for drug companies. Many of the hoped-for treatments have failed in the eleventh hour, including Eli Lilly ’s solanezumab, which failed to meet endpoints in a Phase III trial last year.
Earlier this month, Merck pulled the plug on a Phase II/III study of verubecestat, a BACE inhibitor, for use in patients with mild-to-moderate Alzheimer’s disease. Merck said it stopped the study after an external data monitoring committee determined there was “virtually no chance of finding a positive clinical effect.” That’s not the end of Merck’s verubecestat though. The company said it will continue another study evaluating verubecestat in people with prodromal Alzheimer’s disease.
Andrea Pfeifer, chief executive officer of AC Immune, said drugmakers must redouble efforts to “combat one of society’s biggest challenges” in the wake of “recent disappointing results of other therapies.”
“We remain confident about the potential of crenezumab given it is distinct from other beta amyloid antibodies, predominantly blocking oligomers in the brain, and has a clinical development program that is using higher dosing and targeting earlier stages of Alzheimer’s disease,” Pfeifer said in a statement.
Crenezumab has also had its share of problems. In 2014, the drug failed to meet endpoints in a Phase II study of Alzheimer’s patients. But, after looking at parameters, the company moved forward with additional testing. Crenezumab is a fully humanized IgG4 monoclonal antibody that binds all forms of misfolded Abeta proteins, but especially to Abeta oligomers, to prevent and break up Abeta aggregation and promote Abeta disaggregation, according to AC Immune data. In its statement, AC Immune said there is strong scientific evidence that suggests the idea those oligomers are the “toxic form of Abeta and may be primarily responsible for neurotoxicity when compared to monomers and fibrils of the misfolded Abeta protein.”
Not only is Genentech moving forward with crenezumab, Boston-based Biogen is still banking on amyloid-targeting drug aducanumab. Last year, the company announced positive results from its Phase Ib trial. Late-stage data will not be available for a few years and that is where many Alzheimer’s drugs have failed to meet their goals.
