Roche’s bet on the resurrection of Alzheimer’s disease candidate gantenerumab has flopped. The drug candidate failed to improve the rate of cognitive and functional decline in a pair of phase 3 clinical trials, delivering yet another blow to the field.
Gantenerumab failed a phase 3 Alzheimer’s clinical trial in 2014 only for Roche to bring the anti-amyloid beta antibody back from the dead three years later and move it into a pair of new late-stage studies. After enrolling 2,000 people and tracking them for more than two years, Roche now has data from the studies, GRADUATE I and II. The news is bad.
Roche linked its asset to a numerical slowing of clinical decline, as measured on the Clinical Dementia Rating-Sum of Boxes, in both studies, but the difference fell short of statistical significance. The relative reductions in clinical decline in GRADUATE I and II compared to placebo were 8% and 6%, respectively.
The results were a “resounding failure for gantenerumab,” analysts at financial services group ODDO BHF said in a note this morning.
The Swiss drugmaker will present top-line findings of the data at the end of the month but has already shared a sample that may be implicated in the failure. Specifically, the level of beta-amyloid removal was lower than expected. If, as some companies believe, lowering beta amyloid will improve outcomes, the underwhelming level of removal of the protein could explain the failure of the clinical trials.
In a statement, Levi Garraway, M.D., Ph.D., Roche’s chief medical officer, called the news “disappointing,” adding that “the GRADUATE results are not what we hoped.” Roche used the statement to reaffirm its commitment to Alzheimer’s, noting that it has a pipeline of prospects “for different targets, types and stages of the disease,” but the back-to-back failures of crenezumab and gantenerumab have set it back.
The company's failures sandwich more encouraging news from Eisai and Biogen, which, in September, reported hits on the primary and secondary endpoints in a phase 3 clinical trial of their amyloid candidate lecanemab. After 18 months, lecanemab slowed cognitive decline by 27% compared to placebo, far exceeding the change seen after a longer period in recipients of gantenerumab.
Bill Anderson, CEO of Roche Pharmaceuticals, appeared to take encouragement from the lecanemab readout prior to seeing the gantenerumab results. In a third-quarter earnings call Oct. 18, Anderson noted that the “raging debate as to whether targeting [amyloid beta] does anything whatsoever to clinical signs and symptoms of Alzheimer's … surely has to take on a different character and certainly reassures us in the validity of the pathway.”
But following today's revelations, the ODDO analysts said they expect Eisai's lecanemab “to be alone in the coveted Alzheimer's market.” Shares in Roche fell 4% in the early hours of trading in Switzerland to 313 Swiss francs ($330).