Roche is planning new trials of its Alzheimer's disease (AD) drug gantenerumab, despite an earlier phase 3 failure and a rising body count among other drugs targeting amyloid beta.
Gantenerumab's original developer Morphosys says its Big Pharma partner is planning not one but two new trials of the drug in early-stage AD later this year, in patients with mild disease as well as those in the "prodromal" or predementia phase. For now, the details of those studies—such as the number of patients and precise enrollment criteria—have not been revealed.
After its first phase 3 trial ended in failure in 2014, the Swiss pharma giant vowed to press on with testing gantenerumab at higher doses, saying it would consult with regulators about the design for new trials.
The 2014 gantenerumab trial missed both its primary and secondary efficacy endpoints, but after further analysis Roche said there was a trend toward a benefit in patients whose dementia progressed most quickly. It started phase 1 trials of a new high-concentration liquid formulation of gantenerumab last year with the aim of showing that a higher dose would be safe enough to bring forward into phase 3.
Nevertheless, it's a high-risk move by Roche, coming shortly after the much-anticipated Expedition 3 trial of Eli Lilly's solanezumab candidate followed the same course as two earlier trials and ended with a crash and burn. Pfizer had a similar outcome with its amyloid-targeting antibody bapineuzumab, and a BACE inhibitor from Merck—designed to interrupt the amyloid pathway further upstream—also fell at the last hurdle.
Roche is not putting all its eggs in one basket, however. Just last month it started a second phase 3 trial of another anti-amyloid candidate—AC Immune-developed crenezumab—despite lackluster data in a phase 2b trial. The decision to push forward with crenezumab also came on the back of tweaks to the dosing regimen.
The litany of failed trials undermines the notion that blocking the formation of characteristic amyloid plaques in the brain would help slow cognitive decline. But faced with the lack of effective therapies for AD and huge numbers of affected patients worldwide, drugmakers are refusing to give up on the hypothesis.
Hints of efficacy in some amyloid trials are helping to keep the multibillion-dollar hunt going, although some argue that is at the expense of other possible targets such as tau protein. In Expedition 3, some secondary endpoints "directionally favoured" solanezumab over placebo, for example. Meanwhile, a phase 1b study of Biogen's aducanumab showed that the drug could clear amyloid plaques from the brains of AD patients, with exploratory results pointing to a dose- and time-dependent slowing of clinical decline.
It will, however, be years before Roche learns whether its gamble on amyloid-busting drugs has paid off. Data from the crenezumab trial aren't due until 2020, and the new gantenerumab trials will likely follow a year or two later at best.
For MorphoSys, news of Roche's continued commitment to gantenerumab ends months of silence and is "great news," according to its chief scientific officer Marlies Sproll.
"We are delighted by the strong commitment to gantenerumab as a potential new therapy for Alzheimer's disease," she said. "Gantenerumab has properties that we believe make it a promising candidate to treat Alzheimer's disease, and we look forward to learning more about these new phase 3 trials."