TauRx Pharmaceuticals is set to test the regulatory bar for approval of Alzheimer’s disease drugs in the post-Aduhelm world. The company was unable to show how its candidate performed compared to the control arm in a phase 3 clinical trial—but it plans to use the data set to seek approval anyway.
U.K.-based TauRx randomized 598 people, with symptoms ranging from mild cognitive impairment to moderate Alzheimer’s, to receive its inhibitor of tau aggregation or placebo. Because the study drug, hydromethylthionine mesylate (HMTM), can cause urinary discoloration that could effectively unblind subjects, participants on placebo received methylthioninium chloride (MTC) twice a week.
MTC is primarily used as a dye and in the treatment of a hemoglobin condition. Researchers have also studied the molecule in the treatment of Alzheimer’s. TauRx picked an MTC dose for its LUCIDITY trial that it expected to have no effect on the disease but was surprised by the data.
“Of those receiving MTC 4 mg twice weekly, the majority were unexpectedly found to have blood levels of active drug above the threshold needed to produce a clinical effect. In the absence of a true placebo, the trial as designed could not determine outcomes on primary clinical endpoints relative to a therapeutically inactive placebo as prespecified,” the company wrote in an Oct. 6 release.
Based on the results, TauRx no longer believes it is “technically feasible” to test HMTM in a valid blinded placebo-controlled trial with clinical endpoints. The company responded to the setback by analyzing the data in terms of the relationship between drug blood concentration and treatment effect, change from baseline and comparisons against historical controls.
TauRx designed the trial to assess the effect of daily doses of HMTM versus placebo against measures of cognitive and functional abilities, namely the ADAS-cog11 and ADCS-ADL23 scales. After 52 weeks, the company saw changes of 1.3 ADAS-cog11 units and -1.0 ADCS-ADL23 units in people who took 16 mg of HMTM a day. According to TauRx, untreated patients would typically decline by 5 units on both scales.
The biotech presented subgroup analyses, splitting the population up based on symptom severity, and looked at secondary endpoints to try to build the case that HMTM is effective. TauRx plans to file for approval of HMTM, which failed a phase 3 Aricept combination trial in 2016, in the U.S. and Canada next year on the strength of the LUCIDITY data.