‘Blue Pee’ Saga Continues: Scientists Still Skeptical About TauRx Alzheimer’s Pill

TauRx’s experimental drug HMTM is designed to target tau protein, an Alzheimer’s biomarker protein that causes tangles to muck up the works in the brain. HMTM (hydromethylthionine mesylate), TauRx says, would prevent these tau tangles from forming. If it works, it could become the world’s first oral disease-modifying Alzheimer’s therapeutic. The problem is, it has failed to meet its objectives in three previous Phase 3 clinical trials.

At the AD/PD 2024 conference in March, drugmaker TauRx presented a new analysis of its previous Phase 3 trial. It was an exciting turn of events for HMTM: The new data analysis from this trial supported the company’s claim that, in fact, this experimental drug does actually work. 

Of course, there’s an important caveat: The researchers aren’t able to compare the people who took the drug to a placebo group.

In 2022, the company stated that the drug turns your pee blue and the placebo was also broken down in the body into the active form of the drug. The lack of a “control group” in this trial has made outside experts skeptical of the encouraging new results.

Inside HMTM’s Phase 3 trial, LUCIDITY

In a phase 3 clinical trial called LUCIDITY, trial administrators tested different doses of HMTM across 598 people with mild cognitive impairment or mild-to-moderate Alzheimer’s. But the fact that the drug turns participants’ urine blue added a little complication when it came to finding a placebo that had the exact same effects.

While the study provided some evidence that the trial slowed cognitive decline and reduced brain atrophy, there was one big problem. Their placebo — intended to turn pee blue but remain biologically inert — was metabolized into the active drug by the body. Per the press release, the company does not believe a placebo-controlled trial would be feasible. 

In the new analysis, the company looked at a subset of people from the study who took drugs over the course of two years. Rather than comparing the placebo group, where there are no significant differences, the company compared their data to participants in other studies that received a placebo treatment. Together, the company suggested that the drug reduced brain shrinkage and led to improvements in cognition. 

Clinicians who weren’t involved in the study say they don’t buy it. Dr. Lon Schneider from the Keck School of Medicine at USC told AlzForum that some drug companies do this when they don’t have “significant clinical outcomes from their randomized trials” adding that it’s a “can’t-miss strategy” for finding something positive in a trial where there appears to be no benefit from a treatment. “We should do better in reporting trial results,” he said.

Will TauRx apply for HMTM’s FDA approval? 

Although TauRx representatives have stated they intend to start speaking with drug regulators in the U.S. and EU, the company hasn’t been explicit about when it will file the new drug application. The company also stated they were in the planning stages of applying for approval in 2022.