Two experimental drugs from Eli Lilly and Roche have failed a clinical trial testing them as treatments for a form of Alzheimer’s disease caused by certain genetic mutations, the companies reported Monday.
The study, sponsored by Washington University, tested the drugs in patients who have an early onset, inherited form of Alzheimer’s called autosomal dominant. It’s rare, accounting for less than 1 percent of cases. The hope was that early treatment of patients who have these genetic mutations could slow the appearance of Alzheimer’s symptoms.
Lilly (NYSE: LLY) and Roche reported that the groups treated with their respective drugs did not beat a placebo in slowing decline as measured by tests of memory and cognition. No new safety problems were reported. The companies said more data and analysis would be presented at the Advances in Alzheimer’s and Parkinson’s Therapies meeting in Austria in April.
The Lilly drug, solanezumab, and the Roche drug, gantenerumab, are antibodies designed to bind to and remove beta amyloid, a protein that forms plaques on the brains of Alzheimer’s patients. While amyloid is a hallmark of the disease, targeting it is an approach that has been largely unsuccessful in clinical trials, with the exception of the recent success reported by Biogen (NASDAQ: BIIB) and its drug, aducanumab. The long list of failed amyloid drugs includes both the Lilly and Roche antibodies.
Lilly’s solanezumab had previously failed in 2012 in Phase 3 tests in patients with mild-to-moderate Alzheimer’s. Four years later, Lilly reported another clinical trial failure in patients with a mild form of the disease. Roche stopped a Phase 3 test of gantenerumab in 2014 after an independent committee concluded that the clinical trial was unlikely to be successful. That study evaluated the drug in prodromal Alzheimer’s patients, those with a very early form of the disease.
The Washington University study followed 194 patients for up to seven years. Patients were randomly assigned to groups given the Roche drug, the Lilly drug, or a placebo. Enrollment included patients who did not yet have Alzheimer’s symptoms as well as those had mild symptoms. As the study continued, the dose of both drugs was increased; the Lilly drug was boosted four times higher while the Roche drug was raised fivefold. Despite the higher doses, the drugs did not beat a placebo.
Based on the results of the latest study, Lilly says it will no longer pursue development of solanezumab in patients who have the inherited form of Alzheimer’s. But the company is continuing a study testing the drug in older patients who have evidence of amyloid in their brains but do not show symptoms of memory impairment.
Meanwhile, Roche says its drug continues to be studied in two late-stage clinical trials in Alzheimer’s patients whose disease is not directly caused by genetic mutations. The Swiss pharma giant is also continuing Phase 2 tests of crenezumab in Alzheimer’s prevention. Last year, Roche and partner AC Immune (NASDAQ: ACIU) announced they would stop two Phase 3 tests of that drug in patients with early Alzheimer’s after an interim analysis concluded the studies would fail.