In a small clinical trial, an experimental drug for Alzheimer’s decreased the rate of loss of patients’ ability to think and care for themselves, pharmacist Eli Lilly announced on Monday.
The results have not been published in any way and have not been widely reviewed by other researchers. If necessary, it is the first time that a positive result has been found in a study called Phase 2, said Dr. Lon S. Schneider, professor of psychiatry, neurology and gerontology at the University of Southern California.
Other experimental drugs against Alzheimer’s have never been tested in Phase 2 tests, going straight to larger Phase 3 tests, or have not produced positive results. The Phase 3 studies themselves have had disappointing results repeatedly.
The two-year study involved 272 patients with brain scans indicative of Alzheimer’s disease. Its symptoms range from mild to moderate.
The drug, donanemab, a monoclonal antibody, binds to a small part of the hard plaques in the brain made of a protein, amyloid, which are hallmarks of Alzheimer’s disease. Patients received the drug by infusion every four weeks.
Participants who received the drug experienced a 32 percent slowdown in the rate of decline compared to those who received a placebo. In six to 12 months, the plaques disappeared and remained, said Dr. Daniel Skovronsky, the company’s scientific director. At that point, patients stopped receiving the drug – instead, they received a placebo – during the study.
The small study needs to be replicated, noted Dr. Michael Weiner, a leading Alzheimer’s researcher at the University of California, San Francisco. Still, “this is great news,” he said. “It brings hope to patients and their families.”
Eli Lilly did not disclose the type of relevant data needed for a thorough analysis, said Schneider. For example, the company provided only percentages that describe declines in function among participants, not actual numbers.
The company will provide this data at a subsequent meeting and in an article in a medical journal, Skovronsky said. Eli Lilly received the results on Friday and was forced to report them immediately, he said, because the results could affect Lilly’s actions.
Dr. Schneider, who served on an independent data security and monitoring board for the study, said he was not allowed to disclose more data than the company provided.
The trial served as a test for the so-called amyloid hypothesis. The idea is that Alzheimer’s is closely linked to the accumulation of amyloid in the brain; if the accumulation of amyloid can be prevented or reversed, the disease can be prevented or cured.
Pharmaceutical companies have spent billions of dollars testing anti-amyloid drugs to no avail, leading many experts to believe that the hypothesis is wrong – or that the only way to treat Alzheimer’s is to start very early, before there is any clinical sign of the disease.
The Eli Lilly trial recruited patients not based on symptoms, but on tests that showed significant accumulations of amyloid in their brains. The researchers also performed scans for a protein, tau, which forms spaghetti-like tangles in the brain after the onset of the disease.
“We needed a mild to moderate tangle pathology, but not so many tangles that perhaps the disease is beyond hope,” said Skovronsky.
The primary endpoint, or objective of the trial, was a measurement that combined performance on mental reasoning and memory tests with assessments of how well the participants performed in activities of daily living, such as dressing and preparing meals.
The main side effect was seen regularly in patients who received experimental monoclonal antibodies to treat Alzheimer’s disease: an accumulation of fluid in the brain. It occurred in about 30% of patients, said Skovronsky, but most had no symptoms. The effect was seen in brain scans.
While the test was underway, Eli Lilly started a second Phase 2 test, Trailblazer 2, hoping that the initial effort would yield results. These results are expected in 2023.
Dr. Skovronsky said that Eli Lilly would talk to the Food and Drug Administration and regulatory authorities in other countries about how to help patients gain access to the drug.
“The data is certainly exciting,” he said. “But we will have to see what the regulators say.”
He has been waiting for 25 years for definitive evidence that the amyloid hypothesis is correct.
“This is what we were hoping for,” said Skovronsky.