The mid-stage study missed its primary goal, and the drug's lowest dose outperformed higher doses in ways the company cannot yet explain
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Biogen $BIIB stock fell as much as 8.2% on Tuesday after detailed results from a mid-stage trial of its experimental Alzheimer's drug diranersen raised questions about the relationship between dose and benefit. The decline was the steepest intraday drop for Biogen stock since March, according to Bloomberg.
The company presented full data from the Phase 2 CELIA study at the Alzheimer's Association International Conference in London on Tuesday. The trial had previously been disclosed as missing its primary endpoint, which tested whether higher doses produced greater slowing of disease progression. The detailed data now show the drug's lowest tested dose — 60 mg administered every six months — produced the strongest results on several measures of cognitive and functional decline, while higher doses performed worse, a result that runs counter to what the company had anticipated.
Patients receiving the 60 mg dose declined 26% more slowly than those on placebo on the Clinical Dementia Rating Sum of Boxes, a standard measure of Alzheimer's progression. On two other cognitive measures, ADAS-Cog13 and MMSE, the 60 mg group showed 42% and 50% slower decline, respectively. Patients on higher doses fared less well across those same measures, though the drug did reduce tau — a protein linked to cognitive decline — in cerebrospinal fluid by 50% to 65% across all dose groups. Diranersen is the first tau-targeting therapy to demonstrate reductions in both spinal fluid tau and brain tau pathology as measured by imaging in a Phase 2 study, the company said.
The disconnect between tau reduction and clinical benefit at higher doses is a central puzzle. Brian Abrahams, an analyst at RBC Capital Markets, said in a note to investors that the findings "leave more questions than answers," adding that the reasons for the strongest benefit appearing in the lowest dose arm remain unclear, according to Bloomberg.
David Knopman, a neurologist and Alzheimer's expert at the Mayo Clinic, said the results were nonetheless sufficient to proceed to a late-stage trial, provided the company develops a clearer understanding of dosing. Biogen said it plans to advance diranersen into Phase 3 development.
Shares of Ionis Pharmaceuticals, which licensed diranersen to Biogen, fell as much as 3.3% on Tuesday. The drug targets MAPT mRNA to reduce production of tau protein, a mechanism distinct from approved Alzheimer's therapies such as Leqembi, which targets amyloid.
The Monday rally of roughly 5% that preceded Tuesday's selloff was tied to FDA clearance of a home-administered starting regimen for Leqembi, according to The Wall Street Journal. Biogen has been broadening its pipeline through acquisitions as biosimilar competition erodes sales of older products.
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