- Eli Lilly executives on Thursday said they expect a closely watched preventive study of the pharma's Alzheimer's disease drug solanezumab to yield results this quarter. The university-sponsored trial, called DIAN-TU, is testing patients with genetic mutations that cause early and severe cognitive declines.
- Company leaders, though, tempered optimism the trial will show evidence of slowed Alzheimer's progression, pointing to the study's small size and severity of disease. "It's factors like that that could make it difficult to know what is the truth," Lilly science chief Daniel Skovronsky said on a conference call.
- Executives also said they will watch the Food and Drug Administration's response to Biogen's effort to win approval of rival drug aducanumab. They don't, however, expect the agency's actions would spur a "pivot" in their clinical program that includes two other Alzheimer's therapies.
A persuasive benefit in DIAN-TU could enable Lilly to submit solanezumab for FDA review, more than three years after the last company-sponsored test of the drug in a broader Alzheimer's population failed.
Unlike those earlier trials, DIAN-TU, which is coordinated by Washington University in St. Louis, is a trial of solanezumab in patients with a set of mutations that drive the production of amyloid beta and result in early onset of disease.
The dominant theory of Alzheimer's disease, for the past decade at least, has been that amyloid beta accumulation in the brain leads to the disease's characteristic memory loss and other cognitive disability. But the repeated failure of drugs like solanezumab, which binds with amyloid beta, has cast doubt on that hypothesis.
DIAN-TU enrolled just 490 patients, relatively few compared to the more than 2,000 that Lilly enrolled in EXPEDITION 3, its last solanezumab study. That's due in part to the relative rarity of the mutations that can drive early onset disease — an estimated 5% to 10% of early onset cases are due to the three mutations studied in DIAN-TU.
Nonetheless, its small size is one of the reasons Skovronsky cited Thursday when preparing Wall Street analysts for the possibility the study fails.
In DIAN-TU's favor is the use of a custom composite endpoint that combines a number of cognitive tests typically used in Alzheimer's disease. Failure to show benefit on one test, therefore, may not lead to an overall study miss.
DIAN-TU researchers are also using a much higher dose of solanezumab than in previously trials — another possible advantage.
Moreover, the FDA might be more inclined to review DIAN-TU even with mixed data because its genetic focus makes the targeted patient population orphan-like, rather than the millions of Americans who aren't genetically predisposed to develop Alzheimer's.
Biogen, meanwhile, is pressing ahead with an aducanumab submission based on mixed and hotly debated data. Whether the FDA accepts and reviews the company's application could signal how open the agency will be to a solanezumab submission or, further out, Lilly's Phase 2 projects donanemab or zagotenemab.
However, Skovronsky said Lilly wouldn't be drastically altering its clinical program based on the aducanumab outcome. "We've placed some important bets," he said.
Another preventive trial of solanezumab, called A4, is underway in pre-symptomatic patients with signs of amyloid accumulation. This trial will not yield results for years, however, because the stage of Alzheimer's development requires longer follow-up, Skovronsky said.