For years, hopes have been raised and then dashed in the search for a cure for Alzheimer’s as drugs that pass stage 2 clinical trials fail in stage 3–the last stage of testing before drugs are taken to market. Now two leading drug companies, AstraZeneca PLC and Eli Lilly & Co, have decided they’re not waiting around for potential failure: This week they called off two stage 3 trials for their own experimental drug after an independent review.
The drug, called lanabecestat, targeted beta-amyloid, the protein that builds into plaques in the brains of Alzheimer’s patients. Over 3,000 participants with early and mild Alzheimer’s were enrolled in the trials. The drug is what’s known as a BACE inhibitor—a compound that stops the enzyme that encourages the development of beta-amyloid.
But an independent review concluded that the drug would not mean its goals. Phase 1 studies in 2013 and 2014 showed that the drug did reduce beta-amyloid, the company reported, though the results were not published in a peer-reviewed journal. The company then began a Phase 2/3 trial called AMARANTH in over 2,200 patients with mild cognitive impairment or mild Alzheimer’s. Those participants were separated into three groups: one group was given 20 mg of the drug; another was given 50 mg; and a third was given a placebo. Patients were to be given periodic tests to track how the beta-amyloid was progressing in their brains.
A second Phase 3 trial called DAYBREAK-ALZ started in July 2016 with almost 1,900 participants with mild Alzheimer’s. It also compared two different dosages to a placebo group, and would have ended in 2021.
The halting of the trials calls into question whether beta-amyloid is really the reason behind Alzheimer’s. While it’s considered the leading theory on why Alzheimer’s develops, lately some experts have cast doubt on whether beta-amyloid holds the key to unlocking the origins of this disease. Late last year, Bill Gates personally committed $100 million to “less mainstream approaches” for finding a cure to Alzheimer’s. Other researchers think it’s inflammation, not beta-amyloid, that causes dementia. Still others are in what’s known as the “tau camp”—a group of researchers who believe the protein tau, which forms into tangles in the brains of Alzheimer’s patients, is the reason behind the disease.
Alzheimer’s drugs have over a 99 percent failure rate, and it’s a field that has not offered much hope over the last few years. Pfizer announced in January that they would stop looking for drugs for Alzheimer’s and Parkinson’s altogether. Lilly sunk over a billion dollars into research for a drug they shelved in 2016—but they’re not calling it quits altogether.
“We won’t give up on finding a solution for Alzheimer’s patients,” Daniel Skovronsky, president of Lilly Research Labs, said in a joint statement.