- Biogen shares spiked by as much as 20% Friday on unexpected news one of its experimental Alzheimer's drugs showed some signs it may work as intended in patients with early symptoms of the memory-robbing disease.
- The positive clinical results for the anti-amyloid treatment, called BAN2401, come as a surprise after the drug failed to meet its primary endpoint six months ago — leading many analysts at the time to conclude the drug had little chance of succeeding in the trial's final analysis.
- Now, after 18 months of study, Biogen and its Japanese partner Eisai say the highest tested dose of BAN2401 slowed cognitive decline and reduced toxic clumps of misfolded amyloid protein in the brain. But the companies revealed few other details, preventing a fuller assessment of the drug's efficacy.
Biogen and Eisai's results are a rare piece of positive news for a field that's seen setback after setback.
In 2018 alone, Merck & Co., Eli Lilly and Johnson & Johnsonhave all discontinued late-stage trials of drugs designed to prevent the buildup of amyloid plaques in the brain. Targeting amyloid still remains a core hypothesis for how to treat the neurodegenerative disease. Yet the ever-lengthening string of clinical trial failures has raised serious doubts about the approach.
BAN2401's apparent success, then, offers a sliver of hope for the companies and researchers working to prove reducing amyloid benefits can yield clinical benefits.
According to Biogen and Eisai, the highest of five tested doses of BAN2401 led to a statistically significant slowing of disease progression versus placebo at 18 months. Additionally, brains scans done by positron emission tomography (PET) showed a dose-dependent effect of the drug on amyloid accumulation.
The results represent a reversal of sorts from December, when a statistical analysis designed to allow for a more rapid transition into Phase 3 studies failed to show a cognitive benefit after one year — the study's primary endpoint.
On safety, fewer than 10% of patients in any of the five treatment arms experienced brain swelling, a side effect that can occur with amyloid-targeting drugs.
The companies said they would discuss the results with health regulators to "determine the best path forward." It's not clear what direction the companies hope to go in, but the Food and Drug Administration has recently signaled greater flexibility in assessing the efficacy of experimental Alzheimer's drugs.
Biogen and Eisai are jointly developing BAN2401 as well as two other Alzheimer's candidates and split costs as well as any future profits.
Despite the drugmakers' optimism, the results are far from conclusive and several key questions remain.
For one, it's not clear how many patients were given the dose of BAN2401 that achieved statistical significance. Over 850 patients with early Alzheimer's disease were enrolled into the study and randomized to one of five dose regimens or placebo. Only the 10 mg/kg dose, given weekly, appeared to show an impact on cognition.
Additionally, Biogen and Eisai used a custom endpoint, dubbed the Alzheimer's Disease Composite Score or ADCOMS, that blends several other study objectives more frequently used in Alzheimer's clinical trials. Without external validation of ADCOMS, results on the measure could be harder to compare and assess.
It's enough to invite skepticism of the significance.
"With Biogen and Eisai both massively 'long' beta amyloid programs, and heavily invested in giving the results a positive interpretation, we believe more disclosure ... will be required before the value of BAN-2401, or its contribution to the validation of beta amyloid as a therapeutic target, can be assessed," wrote Leerink analyst Geoffrey Porges in a July 6 note to clients.
Porges noted that, as an amyloid-targeting antibody, BAN2401's effect on amyloid plaques should be expected.
Markets, however, responded enthusiastically to the news, sending shares in Biogen as well as several other Alzheimer's-focused biotechs higher.
Mizuho's Salim Syed even speculated that investor bullishness could even carry Biogen's stock price as high as $400 per share. Around noon Friday, shares in the biotech were up about 15% and trading around $344 per share.
Biogen is also in the midst of testing a more closely followed amyloid-targeting antibody called aducanumab. Results from two large, late-stage trials are expected by 2020, and could dramatically affect the biotech's fortunes.
Analysts saw little read-through from BAN2401 to the studies of aducanumab, which binds to a different type of amyloid protein and is being assessed through a more conventional endpoint.