Lilly adds on to biomarker bombardment in Alzheimer's with 2 new donanemab analyses

Ever since the FDA approved Biogen and Eisai’s Alzheimer’s disease treatment Aduhelm, the buzzword among competing companies has been “biomarker.” And that’s just what Eli Lilly has to offer with two new analyses on their candidate donanemab.

Lilly rolled out the new exploratory analyses of a phase 2 clinical trial called Trailblazer at the Alzheimer's Association International Conference Thursday. The first analysis found that patients who received donanemab showed a greater change in amyloid plaque levels, which was “highly associated with less cognitive decline,” according to a statement. In that analysis, Lilly also found that participants who had greater plaque clearance at 24 weeks showed less tau progression.

The second analysis revealed that donanemab rapidly reduces another biomarker that reflects Alzheimer’s disease pathology, called plasma P-tau217.

Alzheimer’s disease is not well understood, but the current thinking is that abnormal proteins called beta amyloid clump together in the brain and disrupt cell function. Another protein, called tau, strings together in the part of the brain involved in memory and forms tangles inside neurons, blocking the communication between the cells. When amyloid builds up into plaques, it pushes the tau throughout the brain.

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Drug developers believe that if they can clear these plaques, they could address the underlying cause of Alzheimer’s. The FDA approved Aduhelm on biomarker data that suggested the therapy had lessened the buildup of amyloid, not that it improved cognitive function in patients.

This opened a window for companies such as Lilly to revive drugs that were deemed unlikely to benefit patients but still may be able to impact the known biomarker.

And now, Lilly is wedging that window open a little more with the new analyses. Donanemab targets a modified form of beta amyloid plaque called N3pG. The therapy was granted a breakthrough tag by the FDA in June, just weeks after Aduhelm's controversial approval.

"We are excited by these promising results, which provide further evidence on the potential for donanemab to slow disease progression for people with early symptomatic Alzheimer's disease," said Lilly’s Mark Mintun, M.D., vice president of pain and neurodegeneration. "Importantly, these data link the mechanism of action of donanemab, plaque clearance, with positive effects on both clinical outcomes and brain tau pathology."

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In the first analysis, patients who had early symptomatic disease but the most severe plaque burden showed the most rapid clearance. Patients who had complete plaque clearance at 24 weeks were able to stop or reduce their dose of donanemab earlier than other patients.

Patients who had early complete clearance of plaques at 24 weeks showed a decrease in the spread of tau in imaging scans done at 76 weeks compared to placebo. This is a predictive biomarker for Alzheimer’s, according to Indianapolis, Indiana-based Lilly.

Earlier results from the phase 2 study were issued in March, showing that donanemab met its goal of improving cognitive dysfunction in patients who had low to medium presence of tau.