The experimental drug donanemab appears to halt the progression of Alzheimer’s disease and slow certain measures of clinical decline, new trial data show. Developer Eli Lilly expects to apply for U.S. approval of the drug by June, the company reported Wednesday. 

In a stage 3 trial, 47% of participants taking donanemab had no decline in measures of disease severity at one year when compared to 29% of those on a placebo. In addition, at 18 months, trial participants who received donanemab were 40% less likely to show a decline in the ability to perform activities of daily living. They also had a 39% lower risk of progressing to the next stage of disease when compared to placebo.

Safety concerns

The trial data revealed safety concerns as well. Like other monoclonal antibody drugs in its class, donanemab works to clear the brain of amyloid plaques, a hallmark of Alzheimer’s disease. But these drugs, including the already-approved Aduhelm (aducanumab) and Leqembi (lecanemab), are also associated with swelling and microbleeds in the brain, a potential side effect known as amyloid-related imaging abnormalities, or ARIA. In donanemab’s stage 3 trial, incidence of serious ARIA was 1.6%, Eli Lilly reported. Two deaths were associated with ARIA and one death was attributed to severe ARIA.

Patient advocacy groups have nevertheless hailed the new trial results. If the new drug is approved, it will give patients living with Alzheimer’s disease much-needed options in a limited treatment arsenal, they said.

‘Strongest’ data to date

“These are the strongest phase 3 data for an Alzheimer’s treatment to date,” Maria C. Carrillo, PhD, Alzheimer’s Association chief science officer, said in a statement. “This further underscores the inflection point we are at for the Alzheimer’s field. The progress we’ve seen in this class of treatments, as well as the diversification of potential new therapies over the past few years, provides hope to those impacted by this devastating disease.”

The Global Alzheimer’s Platform Foundation, which supports expedited Alzheimer’s drug research, also applauded the donanemab findings.

“​​After waiting nearly 20 years for a new treatment for Alzheimer’s, Alzheimer’s patients and their doctors are on the cusp of having another disease-modifying therapy to treat their condition,” GAP President John Dwyer said. “Millions of people with Alzheimer’s and their families have real hope that they will have a brighter future fighting this disease.”

Medicare coverage

The Alzheimer’s Association is pushing hard for Medicare coverage of amyloid-busting drugs and have been joined by U.S. lawmakers and state surgeons general in doing so. 

Notably, Eli Lilly says it will ask for “the fastest path” to traditional Food and Drug Administration approval. The FDA denied its request for accelerated approval in January. The Centers for Medicare & Medicaid Services has pinpointed the fast-tracked approvals of donanemab’s predecessors as a key reason for its decision to strictly limit Medicare coverage for the drug class so far. Eli Lilly has said that it is betting on CMS changing its coverage stance if donanemab and Leqembi receive traditional approval. 

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