Daniel Karlin, MD: FDA Grants Breakthrough Designation to MM120 for Anxiety

Announced on March 7, 2024, the US Food and Drug Administration (FDA) granted MindMed a breakthrough therapy designation for MM120 (lysergide d-tartrate) for generalized anxiety disorder (GAD) after a phase 2B trial met its secondary endpoint.¹ The topline results demonstrated a single oral administration of MM120, 100 µg in GAD, had clinically and statistically significant durability through week 12.

At the end of last year, MindMed announced on December 14, 2023, the phase 2b clinical trial met its primary endpoint—MM120 provided significant and clinically meaningful improvements for GAD after 4 weeks.² Participants only had a single dose of MM120 in a monitored clinical setting with no other therapeutic intervention.

In an interview with HCPLive, MindMed Chief Officer Daniel Karlin, MD, from the University of Colorado School of Medicine, discussed the durable topline data, the significance of the FDA granting MM120 breakthrough designation therapy, and the next steps for research.

“Now, [the FDA Breakthrough is] not the same as a drug approval—it doesn't give us marketing authorization; it doesn't make mm120 an available drug—but what it is an acknowledgment of is that FDA agrees it has the potential to meet an unmet medical need,” Karlin said.

MindMend plans on holding an end-of-phase 2 meeting with the FDA where they can bring questions and plans to see if the FDA agrees with the study design.¹ Afterward, they will start their phase 3 trial in the second half of the year.

At week 12, Investigators observed Clinical Global Impressions - Severity (CGI-S) scores, on average, improved from 4.8 to 2.2 in the 100-µg dose group, shifting them by two severity categories from “markedly ill” to “borderline ill,” at week 12 (P < .004). Furthermore, the team saw the drug’s rapid activity by only day 2 and saw additional improvements in mean HAM-A or CGI-S scores between weeks 4 and 12.

MM120 100 µg demonstrated a 7.7-point improvement over placebo at week 12 (-21.9 vs -14.2; P < .003; Cohen’s d = 0.81). Participants had a 65% clinical response rate and a 48% clinical remission rate up to week 12, an increase from the 50% remission rate at week 4.

“We were really gratified and happy to see that at 12 weeks, the remission rate holds very close to that [as] we saw a 48% remission rate at 12 weeks from a single dose of MM120,” Karlin said. “I'm not sure we could have hoped for any more than that.”

^References

1. ^{MindMed Receives FDA Breakthrough Therapy Designation and Announces Positive 12-Week Durability Data from Phase 2B Study of MM120 for Generalized Anxiety Disorder. MindMed. March 7, 2024. https://ir.mindmed.co/news-events/press-releases/detail/137/mindmed-receives-fda-breakthrough-therapy-designation-and-announces-positive-12-week-durability-data-from-phase-2b-study-of-mm120-for-generalized-anxiety-disorder. Accessed March 13, 2024.}
2. ^{Derman, C. Daniel Karlin, MD: Topline MM-120 Data for Generalized Anxiety Disorder. HCPLive. December 15, 2023. https://www.hcplive.com/view/daniel-karlin-md-topline-data-mm-120-generalized-anxiety-disorder. Accessed March 13, 2024.}