Lilly Eying Upcoming Results from the DIAN-TU Alzheimer's Trial

At their 2019 full-year financial report, Eli Lilly executives said they were expecting results this quarter from a university-sponsored trial of its solanezumab in preventing Alzheimer’s disease. The DIAN-TU clinical trial is being run by Washington University School of Medicine in St. Louis and is designed and coordinated by the school’s Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU).

The focus of the trial, DIAN-TU-001, is looking at drugs that could possibly change the course of the disease. The trial is relatively small, having enrolled only 490 patients. This is only about a quarter of the 2,000 patients Eli Lilly enrolled in EXPEDITION 3, the last clinical trial it completed on solanezumab.

On November 23, 2016, Lilly announced that the EXPEDITION 3 trial of solanezumab did not meet the primary endpoint in patients with mild dementia from Alzheimer’s. They did not show a statistically significant slowing in cognitive declined compared to patients receiving placebo. There were what the company said, “directionally favored” secondary clinical endpoints, as well as the overall study results, but the magnitudes of the differences were small.

The DIAN-TU trial, though smaller, is focused on patients with three mutations that drive early onset disease. About 5 to 10% of early onset cases are the result of those three mutations.

Although interesting, the company executives are tempering any expectations. Lilly’s senior vice president and chief scientific officer, Daniel M. Skovronsky, said, “It’s factors like that that could make it difficult to know what is the truth.”

However, with most everybody focused on what the U.S. Food and Drug Administration (FDA) will do with Biogen’s eventual submission for aducanumab, Lilly executives say they are paying attention as well, although they probably won’t pivot their clinical program.

In March 2019, Biogen and its collaboration partner Eisai, announced they were discontinuing their programs into aducanumab in patients with mild cognitive impairment from Alzheimer’s and mild Alzheimer’s dementia. Then in October they announced that after discussions with the FDA and further analysis of subsequent data in the trials, aducanumab seemed to improve cognition and function at the highest doses of the drug. They plan submission to the FDA in the near future.

It's possible, of course, that the DIAN-TU results will breathe new life into Lilly’s solanezumab program. The trial is using a custom composite endpoint combining several different cognitive tests, meaning that if one doesn’t show benefit, another might, which could give the overall trial a success. The researchers are also using a significantly higher dose of the antibody therapy than in previous trials.

It’s also possible, if the results are promising, that the FDA will be interested in even mixed results because of the focus on genetic biomarkers, which would help identify appropriate patient populations for the therapy.

There is at least one other trial of solanezumab ongoing, the A4 study. It enrolled cognitively normal people with amyloid accumulation—amyloid is the abnormal protein that accumulates in the brains of Alzheimer’s patients and has been implicated in the disease. However, numerous studies of drugs that clear amyloid have failed to show clinical benefit, casting doubt on the amyloid theory of Alzheimer’s.

The A4 trial quadrupled the dose of solanezumab from 400 to 1,600 mg, dosed intravenously every four weeks. However, any readouts of data from this trial are years away.