A successful late-stage trial result for Biogen and Eisai's newest Alzheimer's disease drug lecanemab has the two partnering companies back in the limelight and on a pedestal for showing the drug has the potential to help millions of patients.
But it's hard to ignore the elephant in the room: What did Biogen and Eisai do right this time after the development and rollout of their first Alzheimer's drug Aduhelm fell to pieces? First, here’s a quick side-by-side comparison.
How aducanumab and lecanemab stack up:
|Biogen and Eisai||Biogen and Eisai|
|Early Alzheimer’s, specifically amyloid plaques||Early Alzheimer’s, specifically amyloid plaques|
Population (phase 3 trials)
|Two trials (Emerge, Engage), 3,285 patients||One trial (Clarity AD), 1,795 patients|
Safety (phase 3 trials)
|~35% incidence of brain swelling||12.5% incidence of brain swelling|
Efficacy (phase 3 trials)
|Companies initially discontinued trials due to inefficiency, but then resorted the population to find clinical success in one of the trials and not the other.||Reduced clinical decline (cognitive and functional) by 27% over 18 months versus a placebo|
Regulatory status (U.S.)
|Approved (accelerated — needs another trial result for full approval)||Application accepted under the accelerated approval program with deadline of Jan. 6, 2023|
With one "clean" study — called Clarity AD — compared with the muddied trials that plagued Aduhelm in the late developmental stages, lecanemab looks like it will at least avoid some of that clinical uncertainty that surrounded its predecessor. Those controversies followed Aduhelm into the market, where it struggled to find payer coverage, and ultimately Biogen and Eisai pulled the plug and stopped marketing the drug altogether in June.
This time, Eisai will lead development and regulatory submissions for lecanemab — with Aduhelm, Biogen mostly held the reins.
The amyloid theory: Is it back?
The results for lecanemab brought positive feedback from analysts and executives. GlobalData senior neurology analyst Pippa Salter said the study breathed new life into the theory that clearing amyloid plaques could be a viable treatment for Alzheimer's.
“After multiple failures, and the controversial approval and messy launch of Biogen’s (anti-amyloid beta) mAb Aduhelm, lecanemab has finally demonstrated in a large-scale pivotal trial that targeting (amyloid beta) can be a successful way to treat AD," Salter said in a Wednesday note. "The primary endpoint that lecanemab met in the trial demonstrates that the drug is specifically effective for reducing cognitive decline. This is particularly important to lecanemab’s prospects, as it demonstrates that it has a significant clinical effect, unlike Aduhelm which failed to demonstrate this in its own clinical trials and was approved based on the surrogate endpoint of (amyloid) clearance."
Mizuho analyst Salim Syed determined the results could be enough for a green light from regulators.
"There's enough in the press release that likely allows for regulatory approval and for the debate to largely shift to potential uptake of the product, in our view," Syed said in an investor note Tuesday.
And Louise Chen, an analyst at Cantor Fitzgerald, looked at how these positive results could lift the prospects of other Alzheimer's drugs in the works, specifically Eli Lilly's donanemab, which also targets beta amyloid plaques.
"The news today could potentially change the Street's and physicians' view of the beta-amyloid hypothesis, and hence the market opportunity (including broad reimbursement) for (Lily's) donanemab," Chen said in a note Tuesday.
Executives at Biogen and Eisai expressed relief in seeing the amyloid theory play out in a late-stage trial without the controversy surrounding Aduhelm.
"The lecanemab Clarity AD study results prove the amyloid hypothesis, in which the abnormal accumulation of (amyloid) in the brain is one of the main causes of Alzheimer's disease, when targeted with a protofibril-binding therapy," Eisai CEO Haruo Naito said in a release. "Eisai believes these findings will create new horizons in the diagnosis and treatment of Alzheimer's disease as well as further activate innovation for new treatment options."
Biogen CEO Michel Vounatsos echoed the sentiment.
"The study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease," Vounatsos said in the joint press release. "As pioneers in neuroscience, we believe defeating this disease will require multiple approaches and treatment options, and we look forward to continuing the discussion about the significance of these findings with the patient, scientific and medical communities."