Novel drug MLC901 underperforms against cognitive decline

NEURoaid II (MLC901), a traditional Chinese medicine-based neuroprotective intervention under investigation, is safe to administer in patients with vascular cognitive impairment no dementia (VCIND), but does not seem to grant significant cognitive benefits, according to a recent Singapore study.

“It could be, and this hypothesis is to some extent supported by the multiple regression analysis, that there is a greater chance to be able to detect a treatment effect in patients who have worse baseline scores,” the researchers said. “[A]fter this pilot study, we believe that future trials should be performed in more severely impaired patients.”

Enrolling VCIND patients from Singapore (n=67), Vietnam (19), and the Philippines (n=17), the multicentre, double-blinded, randomized, placebo-controlled trial looked at the impact of MCL901 on executive function, measured by the Verbal Fluency (VF) and two-part Colour Trails Test (CTT). Twelve- and 24-week changes were compared against placebo controls.

At baseline, the score on parts 1 and 2 of CTT were 128.2±60.4 and 199.6±50.2 seconds, respectively, among MCL901 recipients. Corresponding scores in the placebo arm were 113.6±62.4 and 180.5±56.8 seconds. VF scores in the Animal (VFA) and Food (VFF) subscales were 11.1±4.03 and 11.0±3.94 in treated participants, and 10.2±3.75 and 10.8±4.12 in controls, respectively. None of the differences were statistically significant. [Alzheimers Dement 2021;7:e12161]

NEURoaid II failed to demonstrate significant efficacy. From baseline to week 12, the mean difference in CTT1 improvement between the treated and control groups was only 3.8 seconds (95 percent confidence interval [CI], –9.0 to 16.5), which further decreased to 2.8 seconds (95 percent CI, –8.4 to 14.0) by week 24.

The 12-week improvement in CTT2 seemed to be better in the MLC901 arm with borderline significance (mean difference, 10.9 seconds, 95 percent CI, –0.2 to 22.0; p=0.055), but this effect decreased by week 24 (mean difference, 4.4 seconds, 95 percent CI, –8.2 to 16.9).

Similarly, the investigational intervention had no clear impact on VF. By week 24, VFA scores were 10.6±3.45 and 10.9±3.82 (p=0.67) in the placebo and MLC901 arms, respectively; corresponding scores for VFF were 11.0±4.22 and 11.5±4.01; p=0.53.

Despite the lack of clear impacts, NEURoaid II was safe to use, and there was no significant between-arm difference in the proportion of patients who developed adverse events. Six such events were deemed possibly linked to the intervention, including neuropathic pain at the left face and arm, sleepiness, vomiting, and dizziness.

Notably, exploratory, hypothesis-generating analyses showed that NEURoaid II had limited but significant efficacy in both CTT and VF measures among participants who had greater impairments at baseline.

“A larger clinical trial with longer follow duration in subjects with executive function impairment at baseline could improve the possibility of detecting the treatment effects of MLC 901,” the researchers said. “The results from this study could help to design and characterize the type of subjects to be included in future clinical trials.”