More than 12 hours since Eisai and Biogen announced a phase 3 victory for their Alzheimer’s drug lecanemab, much of the biotech world has become completely giddy.
And rightfully so (should the raw data ultimately match the press release's version). The two pharma partners found that lecanemab slowed disease progression among patients with mild Alzheimer’s by 27% compared to patients given a placebo, with effects starting at six months and continuing through the remainder of the study. Alzheimer’s progression is measured using a cognitive scale that assesses six areas: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care.
Naturally, the biggest industry winners are the two companies developing the drug. But because of the breadth of the race to treat Alzheimer’s, they aren’t the only ones feeling the wind at their backs. The results also provide the most significant piece of validation yet for the hypothesis that targeting amyloid plaque buildups in the brain can stave off Alzheimer’s symptoms, with Eisai’s CEO writing in the company’s release that the results “prove” the hypothesis.
If so, that’s promising news for Roche and Lilly, which are each honing in on the same target with monoclonal antibodies of their own.
The plaque buildups come when amyloid beta proteins in the brain misfold themselves in between nerve cells. Eisai reported that lecanemab also met key secondary endpoints, which include the reduction in amyloid levels in the brain compared to placebo.
Analysts at SVB said that the topline results, plus consistency across all secondary endpoints, “would provide strongly persuasive data for the first time to support amyloid as a key component of Alzheimer's.” They added that they expect this readout will “invigorate” the Alzheimer’s community and focus investors on Lilly and Roche. RBC Capital Market analysts came to a similar conclusion, noting that the results likely validate brain scans measuring amyloid levels “as a surrogate marker for disease.”
In a statement, Roche and Genentech’s head of neurodegeneration, Rachelle Doody, M.D., said her team was “encouraged” by the results from Eisai and Biogen.
“The data will provide important insights around the role plaque removal plays in modifying Alzheimer’s disease,” she said. The company expects topline results from a phase 3 study of its own Alzheimer’s med, gantenerumab, in the fourth quarter. It will also be presented at the Clinical Trials on Alzheimer’s Disease (CTAD) conference at the end of November.
A statement from a Lilly spokesperson said, “These data further establish the importance of lowering beta-amyloid plaques in the treatment of Alzheimer’s disease.” Previous data on the company’s monoclonal antibody, donanemab, found that it was able to reduce amyloid plaque levels, which it says it expects to replicate in the ongoing phase 3 trial.
But while the magnitude of Eisai and Biogen’s results should not be undersold in terms of general progress toward slowing the pace of Alzheimer’s, debate is already underway about how statistical significance in the trial will translate to clinical meaningfulness. The 27% reduction in clinical decline represented a reduction on the cognitive scorecard of 0.45.
RBC noted that key opinion leaders had previously said that a reduction between 0.3-0.5 would translate to clinical meaningfulness. Robert Howard, M.D., a professor of old age psychiatry at the University College London, tweeted that the range for minimal clinically important differences was between 0.5-1.0.
“Scientifically, this is wonderful news,” Howard wrote. “Clinically and practically, it’s going to be very difficult.”
Eisai has said that it will continue to pursue accelerated approval for the drug before asking for full marketing approval in the first quarter of 2023. In the meantime, analysts are looking forward to additional data being presented at CTAD.