Dive Brief:

• Biogen on Thursday touted "unprecedented and compelling" results from a Phase 2 study in early Alzheimer’s disease even though the trial failed to meet its primary endpoint.
• The main goal of the "Celia" study was to find a dose response for the drug, known as BIIB080 or, more recently, diranersen. Researchers instead saw evidence that BIIB080 could slow cognitive decline across all doses, but particularly with the lowest one.
• Biogen said the experimental medicine also successfully reduced levels of tau, a protein that builds up into destructive tangles in the brains of Alzheimer’s patients. The company didn’t release any detailed results, but noted that full findings would be presented at the upcoming Alzheimer’s Association International Conference in July.

Dive Insight:

The conflicting results left some investors and analysts scratching their heads. After an initial premarket bump in the stock, Biogen shares fell about 5% Thursday morning.

Any new method of successfully targeting Alzheimer’s and delivering cognitive benefits to patients could be a “big long-term win,” RBC Capital Markets analyst Brian Abrahams wrote in a note to clients. But it’s too soon to tell if Biogen’s drug will meet that bar.

The company’s enthusiasm and plans to move onto the kind of experiments that can tee up an approval application “suggests there may be something here,” Abrahams wrote. Yet, "with scant detail on the actual effect size, oddities around dose dependence, and an administration profile that will likely need to be improved for optimal commercial viability, we maintain our restraint.”

BIIB080 represents a potentially pioneering new way to attack Alzheimer's. It's a type of genetic medicine — an antisense oligonucleotide — designed to block the cellular instructions that cause the body to produce too much tau, in turn reducing the protein's toxic effects both inside and outside of cells. Ionis Pharmaceuticals originally developed the drug, with Biogen getting ahold of worldwide rights to it in 2019 through a licensing option.

Since that licensing, BIIB080 has become one of the more closely watched assets in Biogen's pipeline. The company posted revenue declines over much of the past five years, and has been trying to tailor its neuroscience research to focus on programs with the highest likelihood of success.

The placebo-controlled portion of Biogen's study followed patients for 76 weeks, with some receiving an active dose of the drug every 12 or 24 weeks. The lowest, 60 milligram dose, was tested every 24 weeks while a 115 milligram dose was tested at both the 12-week and 24-week intervals. Patients got the drug through intrathecal injections, which target the fluid-filled space between the tissues covering the brain and spinal cord.

Generally, researchers expect to see greater effects at higher doses of medicine, contrary to the results Biogen released. “Candidly, we don’t know why the dose response here wouldn’t be linear,” Stifel analyst Paul Matteis wrote in a note to clients. That’s "definitely an open question that will be key to understanding the strength/realness of this signal."

Matteis, like Abrahams, said the results warrant caution. But "the bottom line here is we are somewhat encouraged and are looking forward to seeing the data," Matteis wrote.