We already know Eli Lilly’s big bet on Alzheimer’s disease didn’t work. But a deep dive into just how it failed has provided a bit of encouragement to Biogen and the many companies still hoping to succeed where their rival fell short.
Lilly’s treatment, solanezumab, had no significant effect on the buildup of toxic brain plaques believed by many to be responsible for Alzheimer’s neuron-destroying effects. The company had already disclosed that the treatment failed to improve patients’ cognition and function, but the new data, released Thursday night, shed some important light on the underlying biology.
Here’s why it matters: Lilly’s therapy is among many designed to treat Alzheimer’s by clearing away brain deposits of a protein called beta-amyloid. Doing so, the thinking goes, can at least delay the progression of the memory-robbing disease. Because Lilly’s failed treatment didn’t have a marked effect on those deposits, the so-called amyloid hypothesis lives to fight another day.
This is particularly important for Biogen, which is now in the midst of two huge studies testing an amyloid treatment of its own. In a small, early trial, Biogen’s therapy showed signs that it could improve cognition by blasting away amyloid proteins, and many in the Alzheimer’s field consider it the most promising drug in its class.
Furthermore, the two treatments are quite different. Biogen’s drug, aducanumab, targets plaques once they have already settled in patients’ brains, while Lilly’s was meant to attack the free-flowing proteins that eventually aggregate and form those sticky clumps. And Biogen is testing its therapy in patients in the very early stages of Alzheimer’s, while Lilly pursued those who already had mild dementia.
In data presented at the annual Clinical Trials Conference on Alzheimer’s Disease in San Diego, Lilly’s treatment had only glancing effects on amyloid levels in the brain, beating placebo by too narrow a margin to rule out random chance. But solanezumab did markedly reduce amyloids floating around in the cerebral spinal fluid, suggesting that the problem may have been that it didn’t go after the proteins already clumping in the brain.
“I think this is not a refutation of the amyloid hypothesis,” said Dr. Paul Aisen, a professor of neurology at the University of Southern California. “In fact, I think this is our strongest confirmation to date.”
Solanezumab’s lack of potency is also positive for Merck, which is in the final stage of trials with a pill that takes an upstream approach to the amyloid question. Called a BACE inhibitor, Merck’s drug targets an enzyme responsible for the production of amyloid, seeking to stem the flow of toxic materials at the source.
And, somewhat paradoxically, the news is good for Lilly, too. Solanezumab wasn’t the company’s only Alzheimer’s project. It has a BACE drug of its own, developed in partnership with AstraZeneca, and two more amyloid-targeting treatments in early trials.
Each contender is racing to commercialize the first-ever therapy that can modify the course of Alzheimer’s rather than just treat its symptoms.
The field has a daunting rate of failure, with more than 99 percent of therapies coming up short in the past decade. But the rapid growth of Alzheimer’s, which now affects an estimated 5 million Americans, has presented a multibillion-dollar market opportunity for whoever can finally beat the odds.
Trouble is, there’s no consensus that targeting amyloid will ever show an effect on the progression of Alzheimer’s disease. Many scientists are bitterly divided on the issue, and the drug industry is yet to come up with a molecule that can prove it once and for all.
The next big test of the amyloid hypothesis is still years away, as Biogen isn’t expected to have final data on its treatment until 2019 at the earliest.
The company got some incremental good news of its own at the CTAD conference, as an extension of its earlier trial on aducanumab found that patients who got gradually increasing doses of the treatment experienced similar benefits with fewer side effects compared with those who got one lump injection, according to data presented at the same conference. The results bode well for Biogen’s ongoing Phase 3 studies, analysts said, but with the caveat that it’s still too early to make any conclusions.