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Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation  jcm9144@gmail.com

TauRx reports confusing results with HMTM in Alzheimer’s disease treatment

An odd and confusing result in the 3 Lucidity trial obtained with hydromethylthionine mesylate (HMTM), a tau inhibitor, in Alzheimer’s disease patients, was reported at the Clinical Trials on Alzheimer’s disease (CTAD) conference in San Francisco, on November 2022.

Because the placebo group had received an “active” ingredient the primary endpoints are not reached. But TauRx Therapeutics (Aberdeen, UK and Singapore), the sponsor of the study, claimed:

"We had a treatment effect that is beautiful and remains statistically significant at 18 months after baseline," said Claude Wischik, CEO and executive chairman of TauRx Therapeutics.

For the active intervention, 252 subjects received 16 mg/day of HMTM, and 80  patients received 8 mg/day. However, the researchers faced a dilemma regarding the control group. HMTM causes urine discoloration, which would alert participants that they were in the active group unless the placebo group experienced the same effect. The investigators explored several options and chose a control agent that included an ingredient that shares a parent compound with HMTM: methylthionium chloride (MTC). MTC is the main component of methylene blue which was the original component identified as a tau inhibitor. MTC was  given at a dose of 4 mg twice weekly, the minimum required to prevent bias arising from potential urinary discolouration. At a dose of 4mg/week, the MTC control agent was given to 266 participants.

But in a surprise, "the majority were unexpectedly found to have blood levels of active drug above the threshold needed to produce a clinical effect," the researchers report. So a randomized, controlled, blinded study suddenly saw its control group become a verum group, which did not reach its primary endpoints. However, the bottom line is that this becomes a negative trial. There was not a difference between the low-dose, the placebo group, and high-dose groups.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023 with final data expected to be released next year. To assist with next strategic regulatory issues, TauRx has appointed Dr Richard Stefanacci, an key opinion leader in Alzheimer’s disease, as Chief Medical Officer. Dr Stefanacci commented: “These data support our ability to pursue regulatory submissions. We look forward to making a significant difference addressing this global unmet need with a medication that is affordable, easy to administer, and safe.”

As with Eisai’s lecanemab and Eli Lilly’s donanemab, we are very anxious to see how the U.S. FDA will handle this submission.

 Paris, December 2, 2022

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