It’s hard to say if it was actually a wild ride after the release of Alzheimer’s data, but Biogen shares dropped from $383.83 to $340.84 at the news, although it appears to be rebounding slightly.
There was plenty of anticipation ahead of Biogen and Eisai’s disclosure of data for their BAN2401 at the Alzheimer’s Association International Conference (AAIC) 2018. For example, Geoffrey Porges, an analyst with Leerink, told investors a week ago to prepare for a “wild ride,” noting, “We are hesitant to recommend Biogen’s stock ahead of the upcoming data.”
It’s hard to say if it was actually a wild ride after the release of the data, but Biogen shares dropped from $383.83 to $340.84 at the news, although it appears to be rebounding slightly.
Allison DeAngelis, writing for the Boston Business Journal, noted, “patients taking the highest dosage of BSN2401 … experienced a 30 percent reduction in cognitive decline compared to placebo. Of the patients who received the highest dose of the drug, 81 percent tested negative for amyloid, a plaque that builds up in the brain and is thought to contribute to Alzheimer’s, after 18 months of treatment.”
That would seem to be positive news, although it’s noteworthy that patients on low doses of BAN2401 did no better, and in some cases did worse, than patients receiving placebo. Much of the issue on the part of investors paying close attention to the data is how Biogen and Eisai are analyzing the drug.
DeAngelis writes, “Analysts questioned if the trial results had been impacted by the exclusion of participants who carried the APO4 gene, which has been linked to increased risk of late-onset Alzheimer’s. APOE4 positive patients were not removed from the lower dose and placebo groups.”
Meg Tirrell, a biotech and pharma reporter for CNBC, tweeted last night, “The after-after-hours scuttlebutt on Biogen-Eisai Alzheimer’s data: was the effect in the highest-dose group exaggerated because it had fewer APOE4-positive patients?”
And Geoffrey Porges, an analyst with Leerink wrote, “Confounding the data, the proportion of subjects in the 10 mg/kg q22 arm that were APOE4+ was substantially lower than the placebo arm and other dose groups, which may have impacted the baseline rates of cognitive decline between the various arms and contributed to the appearance of benefit compared to placebo. The reason behind this difference in patient enrollment was due to a request from health authorities outside of the U.S. that APOE4+ subjects be removed from the highest dose arm and randomized solely to the other lower doses of BAN2401 or placebo.”
According to Biogen’s chief medical officer, Alfred Sandrock, at the company’s conference call, the regulatory authorities asked that the patient group be discontinued “due to concerns about safety.” He went on to say that, “Your concerns and mine and all of ours, I think, are going to be largely addressed when we do the sub-group analysis…. Was APOE4 status confounding the results? I think we’ll figure that out soon.”
The two companies expect to meet with the U.S. Food and Drug Administration (FDA) and other regulators to decide on the next steps. Sandrock suggested that more studies will probably be required.
The two companies also announced that another Alzheimer’s drug they are developing together, elenbecestat, cut the amount of amyloid in the brains of Alzheimer’s patients. Beta-amyloid is a protein that accumulates in the brains of Alzheimer’s patients and is believed to be the primary driver of the disease. However, recent clinical trials of drugs that successfully eliminate beta-amyloid have not been shown to improve memory or cognition, casting doubt on the amyloid theory of the disease. This has led many companies developing Alzheimer’s drugs to study patients far earlier in the disease progression.
