番茄社区

NEW YORK CITY -- A single dose of an LSD-containing investigational drug rapidly alleviated symptoms of moderate-to-severe generalized anxiety disorder (GAD), a phase IIb randomized trial showed.

Tested at four doses -- 25, 50, 100, and 200 μg -- the 100-μg dose of MM120 yielded the highest level of clinical activity, significantly reducing Hamilton Anxiety Rating Scale (HAM-A) total score by 7.7 points compared with placebo by week 12 (-21.9 vs -14.2, P<0.003), reported Daniel Karlin, MD, chief medical officer of drugmaker MindMed, at the American Psychiatric Association annual meeting.

Furthermore, 65% of the patients on the 100-μg dose had a clinical response rate (a ≥50% improvement in HAM-A) and 48% were in clinical remission (HAM-A score of 7 or less).

"The idea that a single dose of drug could produce almost 50% remission rate for people suffering from moderate-to-severe anxiety 12 weeks after treatment -- pretty remarkable," Karlin told 番茄社区.

Of note, the 7.6-point reduction in HAM-A with the 100-μg dose at week 4 was more than twice that observed with other GAD treatments, including the recommended first-line treatments, the authors noted in their poster.

In this study, anxiety symptoms significantly improved by day 2 after treatment with both the 100- and 200-μg doses (placebo-adjusted reductions of 1.1 and 0.8 points in the Clinical Global Impressions-Severity [CGI-S] scale score, respectively). These improvements were sustained through the entire 12-week trial. The 100-μg dose also had a 5.73-point greater reduction in Montgomery-Asberg Depression Rating Scale total score compared with placebo.

In March, the FDA granted this investigational treatment a for GAD.

Unlike other psychiatric trials with psychedelics like psilocybin, MDMA, and DMT, MM120 was delivered without the aid of psychotherapy. "We thought it was important to isolate drug effect," Karlin noted. Another reason they chose to design the trial this way was to make the potential move to clinical practice smoother, pending approval.

"If it is approved, we'd like people to be able to add it to their toolbox without having some sort of [mandate]. We just want to make sure people get it safely," he explained. "We believe that the opportunity exists for folks to apply psychotherapy if they want ... and either way, the drug will have coverage."

If MM120 makes it to clinical practice, administration could happen a few different ways, Karlin added.

"I think there could be interventional treatment centers where there are rooms that are running at once and all the way down to individual therapist offices where maybe they could be doing it in a one-to-one setting or group setting," he said. "Our goal is just to open the door to safe clinical use."

The multicenter, double-blind trial enrolled 200 participants ages 18 to 74 with a diagnosis of GAD and a HAM-A total score of 20 or higher at visits 1 and 2. The cohort was divided equally among the placebo, 25 μg, 50 μg, 100 zμg, and 200 μg arms. Among the groups, mean patient age ranged from 38 to 45, 40% to 70% were women, the majority were white, and mean baseline HAM-A score was 29.3 to 31.

Beginning 8 hours after dosing, participants were assessed by the investigator for release and had to no longer meet DSM-5 criteria for hallucinogen intoxication.

Nearly all treatment-emergent adverse events were mild to moderate in severity. Only one serious event occurred that was deemed unrelated to MM120.

The most frequent events that occurred in the group receiving 100-μg on dosing day were illusion (60%), nausea (40%), euphoric mood (27.5%), headache (25%), visual hallucination (22.5%), hyperhidrosis (22.5%), mydriasis (20%), altered state of consciousness (12.5%), anxiety (10%), increased blood pressure (10%), and abnormal thinking (10%).

One participant in the 25-μg group and two participants each in the 50-μg and 100-μg groups had mild or moderate suicidal ideation, but this didn't occur on dosing day. One participant in the placebo group had moderate suicidal ideation on dosing day. Active suicidal ideations developed in one participant in the 25-μg group at weeks 1, 8, and 12 and one participant in the placebo group at week 12.

Based on these findings, Karlin said his team's plan is to move forward with the 100-μg dose for the rest of the clinical program. He noted that they're currently in the process of launching the phase III program, which will consist of two studies, and is slated to start at the end of this year, after MindMed has an end-of-phase II FDA meeting.

Comment