30-Year Alzheimer’s Quest May Soon Bear Fruit

Company focuses on tau protein

Singapore-based TauRx Pharmaceuticals has taken a slightly different approach to finding a treatment for Alzheimer’s disease (AD) than most other companies, according to a report posted on the BioSpace website. TauRx is studying LMTX, a second-generation tau aggregation inhibitor (TAI), in three international phase 3 trials and hopes to present the results as early as July.

The two primary causes of AD are believed to be excess accumulation and “clumping” of beta-amyloid and a protein known as tau. Most drug research has focused on beta-amyloid, but TauRx has targeted tau. Company cofounder Claude Wischik discovered a new class of chemicals in the 1980s, noticing that they dissolved filaments of tau in test tubes.

TauRx has published six papers in technical publications––five during the first half of 2015––that have outlined 10 years of clinical and preclinical work on LMTX.

Although more than 100 failed AD trials were reported between 1998 and 2014, some fairly high-profile companies are also pursuing AD treatments. Eli Lilly, for example, recently announced that it had changed the primary endpoints of its phase 3 study of solanezumab in AD patients. The company said it was shifting its focus to cognition and away from metrics related to activities of daily living. Solanezumab is a monoclonal antibody that appears to help clear the brain of beta-amyloid early in the disease.

Late last year, Biogen reported that it was pivoting away from its successful multiple sclerosis franchise toward Alzheimer’s research. The company is conducting two identical phase 3 clinical studies of aducanumab in a total of 2,700 patients with AD. Aducanumab is another antibody that targets beta-amyloid.

Mid-stage studies of LMTX have shown positive results, although the findings were not consistent with dosing. Patients who received 138 mg per day for 24 and 50 weeks experienced positive cognitive benefits, but patients on a higher dose of 228 mg didn’t have the same results. Wischik believes the discrepancy was related to absorption problems. A newer version of LMTX is being used in the current phase 3 studies.

If LMTX is eventually approved, it could be worth billions of dollars, although it is unlikely to end up being a sole cure for the disease, BioSpace noted. “The consensus of the field,” Wischik said, “is that ultimately some sort of cocktail will be necessary. There’s no winner-takes-all drug.”

Source: BioSpace; March 18, 2016.