Biogen’s Alzheimer’s drug lowers toxic protein, but results were mixed

• The 60 mg dose slowed decline by 26% on CDR-SB (comparable to approved drugs Leqembi and Kisunla), 42% on ADAS-Cog13, and 50% on MMSE cognitive tests
• Diranersen is the first drug to show that lowering tau protein can slow Alzheimer's progression, using a gene-silencing approach rather than antibodies
• Side effects were mild to moderate with no cases of ARIA brain swelling seen with competing amyloid-targeting drugs; the trial included 416 patients over 18 months

Biogen's Alzheimer's Drug Shows Mixed But Encouraging Results

Biogen's experimental Alzheimer's drug diranersen demonstrated significant reductions in toxic tau protein levels but delivered mixed clinical results in a Phase 2 trial involving 416 patients with early Alzheimer's disease.

Key Findings

The 18-month CELIA trial tested three dosing regimens administered via spinal injection. The 60mg dose (lowest) showed the strongest efficacy, slowing cognitive decline by 26% versus placebo on the CDR-SB scale—a 0.54-point improvement. This performance is comparable to approved drugs Leqembi (Biogen/Eisai) and Kisunla (Eli Lilly), which showed 25-30% slowing in their Phase 3 trials.

The drug achieved 50-65% reduction in tau levels across all doses based on brain imaging and spinal fluid measurements, marking the first demonstration that lowering tau can slow Alzheimer's progression.

Mixed Results

The trial missed its primary endpoint of showing dose-dependent response—higher doses paradoxically showed weaker effects. However, the 60mg dose demonstrated benefits on five of six secondary assessment tools, including 42% slowing on ADAS-Cog13, 50% on MMSE, 30% on modified iADRS, and 23% on ADCOMS.

Side effects were mild to moderate, primarily procedure-related (pain, headache), with no cases of ARIA—the brain-swelling condition seen with amyloid-targeting drugs.

Market Implications

Biogen plans to launch a single pivotal Phase 3 trial in 2027, with results expected in 2030-2031. Analysts expressed cautious optimism, with Baird noting the 0.4-point threshold for meaningful therapeutic effect was met. The results may impact competitors developing gene-silencing tau drugs, including Voyager Therapeutics, Arrowhead Pharmaceuticals, and Denali Therapeutics.