- It's unlikely that Biogen Inc. and Eisai Co. Ltd.'s Alzheimer's disease candidate will significantly slow cognitive decline in a Phase 2 trial testing it in patients with early forms of the neurodegenerative disorder, according to an independent committee's analysis.
- BAN2401 missed the placebo-controlled trial's primary endpoint: change from baseline to 12 months in the Alzheimer’s disease Composite Score (ADCOMS), a tool developed by Eisai that helps gauge how well patients respond to treatment. The trial will continue until the 18-month mark, however, at which point investigators will conduct a final evaluation.
- Importantly, the trial used a statistical procedure known as Bayesian analysis to measure BAN2401's success at 12 months. Per that analysis, BAN2401 had to show at least an 80% probability of providing a Clinically Significant Difference (CDS) in the rate of decline in ADCOMS versus placebo. A more traditional kind of statistical analysis will be used at 18 months.
Analysts didn't bet anything big on BAN2401, in part because of how it has performed in this Phase 2 trial.
The trial itself is fairly complex in design, with five active arms, 16 interim analyses for early success, and evaluations at 12 months and 18 months. No interim analysis has resulted in an early stop, raising doubts over BAN2401's efficacy.
To be fair, the Bayesian analysis makes the numbers a little wonky. For example, researchers defined the CDS as a 25% or greater reduction in the rate of decline in ADCOMS compared to placebo. But viewed through a Bayesian lens, the independent committee's findings mean the reduction was less than 38% at the 12-month mark, analysts noted.
Yes, that's kind of opaque, and Evercore ISI analyst Umer Raffat reminded investors in a Dec. 21 note that the trial is not over as more data should come down the pike. He also highlighted that in previous interim analyses the reduction appeared greater than 10% versus placebo, and that Biogen would likely push BAN2401 into Phase 3 if the reduction hit higher than 25%.
Raffat and others didn't expect the results would hurt Biogen stock terribly. Shares in the biotech initially fell by about 4% at market open Thursday before gaining back some of those losses
Salim Syed, an analyst at Mizuho Securities USA LLC, wrote in a Dec. 21 note that the most crucial takeaway from the news is that the independent committee's conclusion doesn't weigh on Biogen and Eisai's closely watched aducanumab.
"Throughout the last several years, we have seen data from other beta-amyloid drugs, and if there is anything that we have learned is that small differences in these antibodies can lead to differences in their efficacy/safety profiles," he wrote in his own Dec. 21 note.
The Phase 2 trial enrolled 856 patients with prodromal or mild Alzheimer’s disease.
"By using Bayesian statistics in this uniquely designed trial we had hoped that it would enable us to demonstrate clinical success faster than more traditional study designs," Lynn Kramer, the chief clinical officer and chief medical officer for Eisai's Neurology Business Group, said in a statement.
"We now await the final study analysis which will be conducted after 18 months of treatment, which represents an amount of treatment time that is considered as appropriate for assessing efficacy in disease modifying agents for Alzheimer’s disease," Kramer said.