On Tuesday, the findings were unveiled during the Alzheimer's Association International Conference held in London. Biogen's drug diranersen is designed to remove tau, a protein inside nerve cells that plays a critical role in Alzheimer's. Existing disease-slowing medicines, such as Biogen's and Eisai's Leqembi, are antibodies that remove a different protein called amyloid.
Earlier reports had indicated that the mid-stage trial failed to achieve its main objective - specifically, that a high dosage would decelerate disease advancement. However, a lower dosage showed greater potential in improving cognitive outcomes.
Additionally, the smallest dose outperformed on several other cognitive tests. Yet the highest dose produced greater reductions in tau.
Ionis Pharmaceuticals Inc., the company that licensed the drug to Biogen, saw its shares slide by up to 3.3%.
Get the market news that matters in a five-minute read with Market Briefs, our free daily newsletter
RBC Capital Markets analyst Brian Abrahams remarked in an investor note that "the findings leave more questions than answers." He added that although the results largely matched predictions, doubts persist regarding the dataset's consistency and reliability.
"The reasons for the most favorable benefits in the lowest dose arm remain unclear, given tau reductions if anything look greater in the higher dose arms," he said. "The effect size even at the optimal dose may not be enough to be viewed as transformative, particularly if larger studies converge efficacy to more of a blend across the three doses studied here."
Mayo Clinic neurologist and Alzheimer's researcher David Knopman commented, "Although the dose issue is difficult to understand, the drug both shows some clinical benefits on some measures and engaged the target." Knopman stated that despite the puzzling dose-response, the data still justifies moving forward with a Phase 3 trial, as long as the firm clarifies which dosage to employ.
Biogen has already disclosed its intention to launch a late-stage study to evaluate diranersen's efficacy and safety.
Alzheimer's disease is characterized by two hallmark proteins: amyloid plaques and tau tangles. While recent approvals like Leqembi target amyloid, tau-targeting drugs aim to disrupt the progression of neurofibrillary tangles that correlate more closely with cognitive decline. Diranersen, an antisense oligonucleotide, works by reducing tau production. The mixed results from this mid-stage trial highlight the complexity of targeting tau, but also underscore the urgent need for effective therapies beyond amyloid.
Should diranersen succeed in upcoming trials, it would be the first Alzheimer's medication authorized that targets tau rather than amyloid, representing a novel therapeutic approach.
Join Market Briefs, our free daily newsletter, for a quick daily rundown of the markets
