Phase 3 trial data for TauRx Pharmaceuticals' experimental drug LMTX revealed no benefit for the majority of patients diagnosed with mild to moderate Alzheimer's, according to results presented Wednesday at the annual Alzheimer's Association International Conference in Toronto.
"We're disappointed," said James Hendrix, director of Global Science Initiatives at the Alzheimer's Association. But, he added, "we learn a lot with every study and it helps advance the field."
While LMTX did not positively impact the majority of patients' scores on tests of mental cognition and daily function, a small group of patients who were not currently using other treatments for the disease were helped by the drug. Over the 15-month study period, 50 or so patients taking LMTX scored better on both cognitive and functional tests, and their brain scans revealed evidence of the disease slowing.
"This is the first time in our field where a drug reduced brain atrophy," said Dr. Serge Gauthier, lead researcher of the study and director of the Alzheimer's disease research unit at McGill University. This "biological difference" in the brain was not accompanied by cerebral microbleeds -- blood in the brain tissue -- a side effect seen with other dementia treatments. "We looked hard, and we cannot find an explanation, but we're pursuing that," said Gauthier.
Dr. Claude Wischik, a co-founder of TauRx Pharmaceuticals, said LMTX is "the first Alzheimer's drug that's clearly shown an underlying effect in the pathology of the disease." Three separate studies conducted by his company -- including the current phase 3 trial -- have shown the same positive effects, though only in patients who are not taking any other standard Alzheimer's treatment.
LMTX attacks the tangles of protein (tau) found in dying and dead nerve cells in patients' brains, a different approach from other Alzheimer's drugs currently on the market. Though disappointed with the current results, Hendrix believes in continued study of tau drugs, since HIV, cancer and other diseases have all achieved some success in an attack-from-all-angles approach. This method may also work for Alzheimer's, Hendrix said.
Tangles vs. plaques
Tangles of tau are a signature feature of Alzheimer's disease. Another is the beta-amyloid protein fragments that accumulate and form plaques between nerve cells in the brain.
When scientists look at tissue from an Alzheimer's patient's postmortem brain, they see not only the unusual plaques and tangles but also surprisingly few brain cells and synapses. Researchers suspect the unusual plaques and tangles may be causing the disease or at the very least contributing to the death of cells.
The formation of plaques is believed to occur much earlier than the formation of tangles, so many scientists have been trying to develop drugs to clear the brain of plaques, explained Dr. Ganesh Babulal, a researcher in the department of neurology at Washington University in St. Louis.
"It's been a beta amyloid-heavy field," said Babulal, who is unaffiliated with the LMTX study but has conducted research
on Alzheimer's and tau. Expectations were high for the drug in part due to the alternative tau approach, he said.
The LMTX trial, a randomized double-blind placebo-controlled study, included 891 patients with mild or moderate Alzheimer's disease in 16 countries. Over a 15-month period, researchers compared results in patients treated with the drug with those treated with a placebo. The results indicated that LMTX was acceptable in terms of safety, similar to other Alzheimer's disease treatments. The most common side effects for patients were easily controlled diarrhea and urinary tract issues, researchers said.
The study, which was funded by privately held TauRx Pharmaceuticals, is currently under review for publication in a peer-reviewed journal, a standard for scientific research.
Gauthier believes there's hope that LMTX may be used to delay the progression of Alzheimer's in its earliest stage. Stage-specific treatments are common to cancer care, he noted, and the future of Alzheimer's care may include prescribing LMTX to some patients.
Nearly 30 years of research has gone into the development of LMTX, according to a statement
from the company. Wischik, who is also a professor of psychiatric gerontology at Aberdeen University, said it's possible the new results could be presented to drug regulators in the United States and Europe.