An encouraging signal on the ability to act on tau protein, but clinical results still difficult to interpret: the new study on Biogen’s diranersen has raised questions among analysts and pushed the company’s stock down. A detailed reading of the data indeed showed some positive elements, but also an unexpected response related to the drug dosage.
PRIMARY OBJECTIVE MISSED
Biogen shares fell after the presentation of detailed results from the mid-stage study on diranersen, which did not meet the primary endpoint of the trial, namely demonstrating that a high dose of the drug could slow disease progression.
The company had already indicated that a lower dose appeared to show more promising cognitive results, keeping attention on the potential of a different approach compared to currently available treatments.
THE DOSAGE PARADOX
The data presented at the Alzheimer’s Association International Conference in London, reports Bloomberg, highlighted an unexpected element: the highest dose of diranersen produced the greatest reductions in tau protein, believed to be involved in Alzheimer’s neurodegenerative processes.
However, some clinical measures showed better results in patients treated with the lower dose, reversing the company’s initial expectations. In the Clinical Dementia Rating Sum of Boxes (CDR-SB), one of the most used parameters to assess disease progression, patients who received the lower dose recorded after 76 weeks an average decline 26% less than the placebo group, while for higher doses the difference was 14% or less.
WHAT THE ANALYSTS SAY
The reaction from analysts reported by Bloomberg was cautious. Brian Abrahams, analyst at RBC Capital Markets, wrote in a note to investors that the results “raise more questions than answers.” According to Abrahams, the data were largely in line with expectations, but doubts remain about the robustness and replicability of the results.
“The reasons why the more favorable benefits were observed in the lower dose group remain unclear, because tau reductions seem, if anything, greater in the higher dose groups,” the analyst stated. “The magnitude of the effect even at the optimal dose may not be sufficient to be considered transformative, especially if larger studies show a more distributed efficacy across the three doses analyzed.”
WALL STREET’S REACTION
After the data release, Biogen shares fell by as much as 8.2% in Tuesday’s session, marking the largest intraday drop since March. Ionis Pharmaceuticals, the company that licensed the drug to Biogen, also saw a decline of up to 3.3%.
THE NEXT STEP IN THE TRIAL
David Knopman, neurologist and Alzheimer’s expert at the Mayo Clinic, emphasized that despite the difficulty in interpreting the dose-response relationship, the drug showed both signals of benefit on some measures and an actual action on the biological target.
“Although the dose issue is difficult to understand, the drug shows some clinical benefits on certain measures and has hit the target,” he said, adding that the results could justify moving to a final trial phase after better dose definition.
Biogen has already announced plans to start a late-stage study to evaluate the benefits and risks of diranersen.
THE CHALLENGE TO AMYLOID
Diranersen, explains Bloomberg, is closely watched because it adopts a different mechanism compared to currently available anti-Alzheimer’s drugs. Treatments like Leqembi from Biogen and Eisai act on amyloid, a protein that accumulates in the brain years before symptoms appear.
Biogen’s drug instead targets tau protein, considered more closely linked to cognitive decline in the advanced stages of the disease. If future results confirm the treatment’s effectiveness, diranersen could become the first approved drug based on a tau-targeted approach against Alzheimer’s.
