A phase 2 trial of Biogen and Ionis Pharmaceuticals’ tau-targeting candidate missed its primary endpoint. But while the Alzheimer’s disease trial failed to yield the hoped-for dose-response data, reductions in tau pathology and cognitive benefits persuaded Biogen to commit to registrational development.
The readout is a big moment for Biogen and the wider field, with Guggenheim Securities analysts hailing the data as the “moment of truth for tau” and predicting it could drive Biogen’s stock up 50% in notes to investors in recent weeks. As is often the case in Alzheimer’s, the implications of the available data are too fuzzy for such a big stock swing, leaving Biogen up more modest 4% at $213.50 in premarket trading.
Biogen lacks investors’ wariness. The data are an “unprecedented and compelling confluence of efficacy and biomarkers results,” Priya Singhal, M.D., head of development at Biogen, said in a statement. Bullish about the data, Biogen plans to move diranersen into registrational development.
BMO Capital Markets analysts were more equivocal, calling the cognitive benefit “a broad positive for Alzheimer’s development” in a note to investors Thursday but cautioning that the lack of specifics on the magnitude of the effect may limit upside for Biogen.
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Biogen and Ionis are yet to share data to back up Singhal’s take, limiting the topline release to qualitative readings of the results. Prespecified analyses of cognitive endpoints linked all doses of diranersen, an antisense oligonucleotide, to a slowdown in clinical decline. The clinical outcomes were supported by “robust” reductions in cerebrospinal fluid tau and tau pathology on all doses.
The slowdown in clinical decline particularly applied to the lowest dose, the companies said. That finding explains the failure of the primary endpoint. Rather than compare diranersen to the placebo arm, Ionis and Biogen used dose response for change from baseline on a clinician-rated dementia scale at Week 76 as their primary endpoint. With the low dose performing strongly, the trial missed its primary endpoint.
Last month, Guggenheim analysts predicted Biogen’s stock would be flat to down 5% if the trial failed to show a dose response but diranersen delivered some benefit over placebo. With Biogen upbeat on the readout, investors took the news better than expected, but questions will hang over the program until the level of clinical benefit versus placebo is revealed.
“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 analysts said.
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Biogen and Ionis plan to share data at the Alzheimer’s Association International Conference in July. The clinical benefit data, as measured on the CDR-SB scale, will be key to evaluating diranersen’s prospects. A 0.6-point benefit over placebo on the scale could drive Biogen’s stock up 50%, Guggenheim analysts said last month, while the share price could be flat to down if the difference is only 0.4 to 0.5 points.
Interest in the data extends beyond Biogen and Ionis. Voyager Therapeutics’ share price rose 10% to $4.57 in premarket trading, potentially reflecting the implications of the diranersen data on its tau program VY1706. The biotech expects to move the tau-silencing gene therapy into the clinic this year.
