Why Biogen's Fate May Depend on Eli Lilly's Alzheimer's Data

October 27, 2016
By Mark Terry, BioSpace.com Breaking News Staff

It’s not quite a horse race. Although some observers believe that Eli Lilly ’s efforts to get approval for its drug solanezumab for Alzheimer’s disease is in direct competition with Biogen ’s efforts to get aducanumab approved, Biogen indicates that Lilly’s approval would set a useful precedent.

Part of the problem has to do with the current state of our understanding of Alzheimer’s disease. There are two primary mechanisms believed to be responsible for Alzheimer’s disease. The first is the development of beta-amyloid plaques in the brain. The other is abnormal tau proteins that cause neurofibrillary tangles. Beta-amyloid plaques are the primary target of choice for most AD drugs, although it doesn’t appear to be the whole story. Some drugs that clear beta-amyloid don’t seem to result in better patient responses. Tau is implicated, but they don’t appear after the formulation of beta-amyloid plaques.

Both solanezumab and aducanumab focus on clearing beta-amyloid plaques, although they use somewhat different mechanisms to do so.

Which is why investors questioned Biogen at yesterday’s third-quarter conference call on whether Lilly’s solanezumab trial would have an effect on their own Alzheimer’s drug trial. Michael Ehlers, head of Biogen’s R&D, responded, “We think if there were positive results out of the solanezumab trial this would give great credence to the amyloid hypothesis of Alzheimer’s disease, and I think it bodes well for the potential results of aducanumab. However, … we believe it will be much more difficult to make a conclusion about a negative result on solanezumab vis-à-vis the potential results of aducanumab.”

Lilly is evaluating solanezumab on more than 2,000 patients with early Alzheimer’s disease. The same drug tanked in a trial in 2012, failing to meet its endpoints. Lilly shifted its strategy and focused on milder forms of the disease and used a “delayed start” method. The delayed start study design is where patients are randomized to the same treatment, but start at different times. This results in two treatment periods, a placebo-controlled one followed by a delayed-start period. Hong Liu-Seifert et al. say that, “If the treatment difference observed at the end of the placebo-controlled period was preserved at the end of the delayed-start period (that is, delayed-start patients do not ‘catch up’ with the early start patients), the treatment effect is considered consistent with a disease-modifying effect.”

Lilly released interim data in July that indicated patients receiving solanezumab, a monoclonal antibody that binds to forms of beta-amyloid, had about a 35 percent improvement in cognition. Not a cure, and effective in only about a third of patients with a milder form of the disease, but better than what little else is on the market.

Biogen has released some updates on Phase Ib trials of aducanumab, which is a human recombinant monoclonal antibody, which is believed to target forms of beta-amyloid including soluble oligomers and insoluble fibrils deposited into the amyloid plaque in AD patient brains. Preclinical and interim Phase Ib data have shown it reduces amyloid plaque levels. Whether that will have an effect on cognitive decline remains to be determined.

Which is at least partly why Biogen may be cheering Eli Lilly on. If Lilly’s data is positive, it’ll support Biogen’s own approach. If Lilly’s data is negative or inconclusive, Biogen will have to prove on its own that its drug works without Lilly’s supporting data.

Charley Grant, writing for The Wall Street Journal, says, “Positive results from the trial would certainly give investors big rewards. But the idea that this potential upside comes without major risks is likely too good to be true.”