Eli Lilly and AstraZeneca Abandon Alzheimer’s Drug
The decision was made after an independent monitoring committee evaluated the results to date and concluded that its primary endpoints were “not likely” to be met. There were no safety concerns.
The two companies say they will continue to work together on a different early-stage drug for Alzheimer’s. Lilly also has other Alzheimer’s drug in ongoing clinical trials.
Lanabecestat is in a class of Alzheimer’s drugs called beta secretase cleaving enzyme (BACE) inhibitors. BACE is a precursor to amyloid-beta, which is believed to be the leading cause of Alzheimer’s disease. However, a number of recent high-profile failures of antibodies that clear amyloid-beta has cast doubt on the amyloid hypothesis. Later in the disease, tau proteins accumulate in the brains of Alzheimer’s patients, but that has not been as intense a focus as amyloid clearance or prevention.
In February, Merck & Co. announced it was halting protocol 019, its APECS Phase III clinical trial of verubecestat (MK-8931) in Alzheimer’s disease. Verubecestat was also a BACE inhibitor. In that case, an external Data Monitoring Committee (eDMC) recommended ending the trial after an interim safety analysis indicated the likelihood of benefits didn’t outweigh the risks.
In May, Johnson & Johnson’s Janssen division ended its trials of atabacestat, a BACE inhibitor. It indicated, similar to Merck, that it was shuttering the program because of safety issues, rather than any question about the drug’s efficacy. Patients in the EARLY Phase IIb/III clinical trial with preclinical Alzheimer’s disease, as well as a Phase II long-term safety trial, had elevated liver enzymes.
Lilly and AstraZeneca teamed up to co-develop lanabecestat in 2014 in a deal that could have hit $500 million. Lilly handled the two trials, one for early Alzheimer’s and the other for patients with a milder version of the disease. AMARANTH was for early Alzheimer’s and DAYBREAK-ALZ was on mild Alzheimer’s disease dementia. AstraZeneca handled manufacturing. The trials were expected to conclude in 2021. There were more than 3,000 patients enrolled. The drug received Fast Track designation in 2016 from the U.S. Food and Drug Administration (FDA).
“The complexity of Alzheimer’s disease poses one of the most difficult medical challenges of our time, and we are deeply disappointed for the millions suffering from this devastating disease,” said Daniel Skovronsky, president of Lilly Research Labs, in a statement.
He went on to say, “We won’t give up on finding a solution for Alzheimer’s patients.”
On the good-news-so-far front, it was only last week that Biogen and Eisai Co. announced that their BASE inhibitor, elenbecestat, had a good safety profile in a Phase II clinical trial and showed a statistically significant difference in amyloid beta levels in the brain. Those levels were measured by amyloid-PET scans. That trial was of 70 patients and as the company noted, is the first trial of a BACE inhibitor to show a statistically significant difference in amyloid beta in the brain while also showing a delay of clinical symptom decline.
“It is highly encouraging that Study 202 confirmed elenbecestat’s treatment effect in reducing amyloid in the brain and suggested a slowing of clinical decline,” said Lynn Kramer, Eisai’s chief clinical officer and chief medical officer, Neurology Business Group, in a statement. “Eisai and Biogen will continue to work together to advance the ongoing Phase III program (MISSION AD) in order to contribute a new potential treatment option to Alzheimer’s disease patients as soon as possible.”