This week, BioArctic Neuroscience, Esai, and Biogen made headlines when they announced via press release the topline and positive results of their Phase 2a study of the anti-amyloid antibody BAN2401. The press release indicated that the drug “demonstrated statistically significant slowing in clinical decline and reduction of amyloid beta accumulated in the brain” in patients with early Alzheimer’s disease.
To be sure, this is welcomed news. Too often headlines for Alzheimer’s disease clinical trials are about “flops” and “failures.” So we should take this good news and embrace it. Unfortunately, there remain many questions to which we need answers before we celebrate too much.
First, this trial was previously considered negative. The investigators from Esai and their partners are to be commended for pushing the envelope. This trial employed a complex modern protocol known as an adaptive design. The adaptive design used numerous planned analyses of data from the ongoing trial to try to “pick a winner” among five doses of the drug, funneling more patients into the best dose. Unfortunately, after enough patients had achieved 12-months of treatment, there was no winner. Despite this, the plan was always to keep the trial going until patients had received the drug for 18-months.
When the trial was analyzed in a more traditional sense, comparing the patients who got drug to the patients who got placebo for the entire 18-months, those receiving the highest dose apparently benefited most. Still, we will need to hear more about all of the groups, including how many patients were in each group and how the groups performed compared to each other. We also need to see the full safety data, though the topline report suggests that the safety profile was as good as some other antibodies in development for Alzheimer’s disease, but worse than some others.
This represents the second time that an investigational agent targeting the fibrillar form of amyloid beta that accumulates in the Alzheimer’s brain has demonstrated promising effects on both brain biomarker and clinical outcomes. These results are heartening. Nevertheless, the secondary nature of the analyses and the need for replication in Phase 3 trials warrant caution, as well as optimism.