- A highly-anticipated experimental treatment for Alzheimer's disease failed to improve cognitive and functional ability in a late-stage trial, delivering a blow to hopes the drug could validate a promising new approach to treating the neurodegenerative condition.
- While the study did not achieve either of its primary endpoints, the company developing the drug, privately held TauRx Therapeutics, found some promise in a subgroup of patients who did see a statistically significant benefit from taking the drug by itself.
- Known as LMTX, the drug is designed to prevent clumping in the brain of abnormal fibers associated with a protein called tau. These so-called "tau tangles" are thought to contribute to development of Alzheimer's. Most Alzheimer's research to date has focused on targeting amyloid plaques, but no drug has been developed yet which actually slows progression of the disease.
Most of the 891 patients in the Phase 3 study took LMTX along with other standard Alzheimer's treatments. Among these patients, no meaningful differences were seen between the treatment group and placebo arm across several standard measures of cognitive and functional ability.
In the 15% of patients who took only LMTX without the other drugs, however, Tau Therapeutics reported a statistically significant benefit in both cognitive and functional assessments. Furthermore, MRI scans of these patients showed a reduced rate of brain shrinkage, suggestive of slowing brain atrophy.
But TauRx doesn't know why the benefit seen in patients taking LMTX as a monotherapy disappeared when patients took other standard treatments. And subgroup analysis can sometimes show benefits which are not present when examined among larger groups of patients.
"The reason for the observed loss of efficacy of LMTX when taken in combination with currently available treatments for Alzheimer’s disease is not as yet understood," said Claude Wischik, a professor of psychiatric geratology at Aberdeen University and co-founder of TauRx.
TauRx's study of LMTX was the first completed Phase 3 trial to examine a tau-aggregation inhibitor. Other pharmaceutical companies, such as Biogen, Abbvie and Eli Lilly, have begun development of their own tau inhibitors, but the field is still young compared to what has been done to study drugs aimed at beta-amyloid.
"In Alzheimer’s, the most likely scenario for successful future treatment is addressing the disease from multiple angles. Having a drug that targets tau complete a Phase 3 trial is a very hopeful sign,” said Maria Carrillo, chief science officer of the Alzheimer’s Association.
Advancing medical understanding of tau is small consolation for TauRx, which had hoped the trial would be a slam-dunk in support of application for approval. TauRx expects results from a second Phase 3 trial studying LMTX in 800 patients with mild Alzheimer's later this year.
Alzheimer's affects roughly 5.4 million Americans, mostly people over the age of 65, according to the Alzheimer's Association. That number is predicted to grow to an estimated 13.8 million by 2050, which would be a huge burden on the healthcare system.