Another monoclonal antibody for Alzheimer’s to get FDA review

The US Food and Drug Administration has granted priority review to lecanemab, an antibody intended to treat Alzheimer’s disease by dissolving amyloid plaques in the brain. Lecanemab marks another attempt by Eisai and Biogen to demonstrate that plaque-busting antibodies are a viable therapy for early-stage Alzheimer’s, despite many researchers saying otherwise.

Priority review means the FDA will act on the firm’s approval application within 6 months instead of 10. Lecanemab’s path to the agency’s door mirrors that of aducanumab, another monoclonal antibody from Eisai and Biogen. Aducanumab generated controversy when the FDA greenlighted it even though clinical trials showed that its cognitive benefits were marginal. Ultimately, Biogen stopped marketing the drug when the US Centers for Medicare and Medicaid Services refused to cover it for people with Alzheimer’s outside clinical trial settings.

While aducanumab requires incremental dosage for the first few months to avoid side effects like brain swelling and bleeding, lecanemab can be started immediately at the highest dose, says Michael Irizarry, Eisai’s vice president of clinical research. “We hope that that would allow faster action in terms of targeting amyloid and potentially, clinical effects,” he says. Lecanemab is currently in Phase 3 trials.

In the meantime, neuroscientists aren’t holding their breath. “None of the monoclonal antibodies have shown efficacy in the past,” says Lon Schneider, a neuroscientist at the University of Southern California. This is because removing plaque in the brains of people with Alzheimer’s has not translated into improvement in their conditions. Schneider expects the latest plaque-clearing candidate will be no different.

Whether eliminating amyloid can treat Alzheimer’s effectively is a matter of timing, says Rudolph E. Tanzi, a neuroscientist at Harvard University. Amyloid accumulation can begin decades before the symptoms of Alzheimer’s manifest, so Tanzi thinks plaque-targeting treatment should start in these earliest stages; by the time cognitive decline kicks in, it’s too late.

Targeting amyloid in a person who already has symptoms of Alzheimer’s is akin to treating someone who needs a coronary bypass with a mere cholesterol drug, he says. “In a perfect world,” Tanzi adds, patients would start taking antibodies preventively when the first plaques might form. But since antibodies can cost tens of thousands of dollars annually, using them preemptively isn’t practical or affordable.

Instead, Tanzi thinks cheaper, repurposed small-molecule drugs are the future. And despite the controversy, the pursuit of antibodies by Eisai and Biogen may clear the way for such chemical compounds to obtain approval down the line, Tanzi says. “The silver lining … is that it opens the door for cheaper, safer drugs that can achieve the same goal of lowering amyloid,” he says. Tanzi and a company he advises, AZTherapies, are screening for drug candidates to pick up where antibodies will leave off.