Biogen leaders took to an investor call today to defend the phase 2 readout of the company’s anti-tau Alzheimer’s disease candidate, which despite slowing cognitive decline on par with approved medicines sparked a significant stock slip.
Biogen’s stock was down about 8.4% when the call began, largely due to confusion surrounding the strong performance of the lowest dose in the phase 2 Celia study of diranersen, an antisense oligonucleotide that binds to the mRNA blueprint for tau protein. Tau is one of the key proteins that becomes deformed and clumped in Alzheimer’s, alongside amyloid.
The success of the 60 mg dose, infused every six months into the spinal fluid, explains why the trial failed its primary endpoint, which was based on a dose-dependent response. Biogen shared the data today at the Alzheimer’s Association International Conference in London.
For Biogen, the results are rather straightforward and clearly support the pharma’s plan to rapidly advance into a pivotal phase 3 study. Diranersen is the first anti-tau drug candidate to ever successfully reduce tau levels in the brain and slow the pernicious cognitive decline of Alzheimer’s. What’s more, it does so similarly to approved anti-amyloid antibodies like Biogen’s Leqembi and Eli Lilly’s Kisunla, but with less frequent dosing and without the risk of dangerous brain bleeding.
“Several aspects of the Celia data are unprecedented,” Priya Singhal, M.D., Biogen’s head of development, said in the call. “We are excited about diranersen’s overall potential to be the first tau-targeting medicine for early Alzheimer's disease.”
The important thing, Singhal added, is that the trial gave Biogen a promising potential phase 3 dose and further proof of concept for diranersen.
Prior to today’s readout, an investigator in the Celia trial and a leader from diranersen developer Ionis Pharmaceuticals both told Fierce that they also view the data as proof-of-concept that warrant a phase 3 push. Diranersen also doesn’t necessarily need to outperform anti-amyloid antibodies, as many experts are excited by the potential to combine therapies addressing the two key disease-causing proteins.
While acknowledging that the lack of a dose-dependent response “raises important questions” for the phase 3 trial’s design, Laura Nisenbaum, Ph.D., interim chief science officer at the Alzheimer's Drug Discovery Foundation, said in a statement that the data are the first to “show a tau-targeting drug producing both a robust biomarker effect and a signal of clinical benefit.”
While all doses performed nominally better than placebo, the 60 mg dose scored the best across a range of clinical cognition tests, and also had the fewest cases of post-infusion confusion, the adverse event that most caught the eye of analysts on the call.
When confusion occurred it was mostly within a week after diranersen was administered, and most cases were mild or moderate and resolved within about another week, Diana Gallagher, M.D., Biogen’s head of immune-mediated and neurodegeneration development, said on the call.
“Typically, it did not lead to study drug discontinuation,” Gallagher said, and confusion seems to be unrelated to tau removal because it appeared well before diranersen had time to exert its knockdown effect.
Biogen’s attempt to assuage investor concern seemed to pay off a tad. From its mark of $191.34 per share at the time the call started, the company’s stock steadily climbed up to $194.87 at 1:45pm E.T., 45 minutes after the call ended.