While Biogen’s tau-targeting therapy didn’t demonstrate improvement on a dementia severity scale, the company touted biomarker and cognitive improvements from the Phase 2 study, leaving analysts eager for more data.
Biogen is moving its tau-targeting therapy to registrational development after seeing biomarker and cognitive improvements in a mid-stage study of patients with early Alzheimer’s disease.
But the company is keeping specifics of the readout under wraps. Biogen did not provide data in its news release on Thursday morning, disclosing only that the candidate, dubbed diranersen, or BIIB080, elicited a “robust biomarker impact” on tau concentrations in the cerebrospinal fluid. Diranersen failed to meet the primary endpoint of the phase 2 CELIA study, which was a dose-response change in disease severity from baseline at 76 weeks, as measured by a clinical dementia scale.
The trial recruited more than 400 patients with mild cognitive impairment due to Alzheimer’s disease or with mild Alzheimer’s disease dementia. None of the study participants had received prior anti-amyloid therapy. Three doses of diranersen were tested against placebo—60 mg every 24 weeks, 115 mg every 24 weeks and 115 mg every 12 weeks.
Despite missing the trial’s main goal, Biogen zeroed in on other signals of efficacy. Aside from the biomarker improvements, the company touted findings from a pre-specified analysis of cognitive endpoints that showed slower clinical decline across all tested doses of diranersen. This effect was strongest at the lowest dose level.
Based on the findings, Biogen plans to take diranersen forward into registrational development, though the company has yet to say when Phase 3 will begin. Detailed data from CELIA will be presented at the Alzheimer’s Association International Conference in July.
Biogen’s stock has ticked up 4% in pre-market trading since sharing the data.
Analysts are cautiously optimistic about diranersen. “Any new mechanism showing cognitive benefits in Alzheimer’s could be a big long-term win,” RBC Capital Markets told investors in a Thursday note, adding that Biogen’s “excitement” over the data “suggests there may be something here.”
BMO Capital Markets, meanwhile, called the cognitive benefits seen in CELIA “a broad positive for Alzheimer’s development,” adding that the findings point to “the possibility of a cognitive benefit from tau targeting treatment.”
Still, the dearth of details is giving analysts pause. “We want to be a little cautious here until we see the full data,” Stifel wrote on Thursday, adding, “Candidly we don’t know why the dose response here wouldn’t be linear, which is definitely an open question that will be key to understanding the strength/realness of this signal.”
RBC agreed, telling investors that “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.” Diranersen is meant to be administered intrathecally—through an injection directly into the spinal column.
Stifel and RBC were both able to get a hold of Biogen management, but said the company is staying tight-lipped about the data.
Broadly, however, the analysts appear supportive of Biogen’s decision to move forward into late-stage testing, with Stifel writing that, “Biogen probably wouldn’t be moving this forward unless it was pretty encouraging.”
For BMO, putting diranersen through late-stage testing will be a good way for Biogen—and the industry more broadly—to clear up some questions surrounding the asset and its efficacy.
“Without a dose response from BIIB080 treatment and no indication of the magnitude of cognitive benefit, we interpret topline results to be supportive that intracellular tau targeting treatment may be addressing some of the drivers of Alzheimer’s, but with more work to be done in a Ph 3 to elucidate this benefit,” BMO said.
