Defying Industry Setbacks, MindMed Advances Psychedelic To Phase 3

By Dan Schell, Chief Editor, Clinical Leader

Is a “constructive” End-of-Phase 2 (EOP2) meeting with the FDA a big deal? Sure it is, because no matter how you define constructive, it likely means things went well and you’re progressing — at some point — to a Phase 3. But it can be a really big deal, especially if the timing of that positive EOP2 comes on the heels of some of the worst press pertaining to the class of drugs you’re developing. That’s the scenario MindMed found itself in back in early June.

The small (i.e., about 70 employees) clinical-stage biopharma has been working on (among other products) an LSD-based drug — MM120 — for the treatment of generalized anxiety disorder (GAD). Like many companies targeting psychedelics such as MDMA and psilocybin for treating mental health conditions, MindMed has been riding the crest of a wave of interest for these types of therapies. The company got good news in March when the FDA granted Breakthrough Therapy Designation for MM120, but the psychedelics industry took a hit on June 4 when the FDA's Psychopharmacological Drugs Advisory Committee voted against approving Lykos Therapeutics’  MDMA-assisted therapy for PTSD. The ripples from that adcom, however, didn’t seem to affect MindMed considering the company announced that constructive EOP2 about two weeks later. “I think everyone expected that after that adcom there was going to be a knee-jerk reaction like we saw in the markets,” says Rob Barrow, MindMed’s CEO. “But even after that news, we’ve had continued positive engagement and significant fundraising from some of the smartest investors and biotech specialists in the world. And, all the pushback items from that adcom are things we saw coming and have been planning to overcome and address since day one in our program.”

STUDY DETAILS & ADDRESSING FUNCTIONAL UNBLINDING

MindMed’s Phase 2B study included 200 patients across five different arms, which included a true placebo, and then four doses — 25, 50, 100, and 200 micrograms — of MM120. The study was conducted at 20 sites throughout the United States.

Trial participants were administered the drug in a private room at the treatment center. For safety, two staff members keep the participants under observation for the duration of the day. “We give them reading and writing materials, music, etc.; the things that you would want to have handy regardless of whether you're on a treatment or not for the duration of the day,” Barrow explains. “Some of the participants, particularly those who get the higher doses, end up laying down and putting on eye shades and listening to music, and it seems like they're almost asleep for a majority of the time.” At the end of the day, they're released to go home with a responsible adult. They come back for follow-up assessments the next day and then at one, two, four, eight, and 12 weeks after the dosing.

Functional unblinding (i.e., participants can guess their treatment assignment) is a concern for any clinical trials involving a psychiatry drug.  If a participant believes — because of how they feel — that they are in the group receiving the drug being tested, they may be more likely to report a good outcome. Conversely, if they don’t feel any differently, they may conclude they are in the placebo group and report negatively about their experience.

To minimize this bias, Barrow says MindMed used centralized raters (the person interviewing the patient) who were blinded not only to treatment assignment but to the visit number. When asked to guess which dosing group a patient was in, often the raters were incorrect.

For example, a third of the patients who got the placebo believed they had received the active drug. Around 85% of the patients who received the 25 micrograms dose correctly guessed that they were on drug; they knew they were feeling something. Nearly 90% of the patients who received the 50 micrograms dose could accurately guess they were on the drug, but they were the worst performing in terms of anxiety symptoms. The 100- and 200-microgram doses had the most robust responses, but patients on the 200-microgram dose had more adverse events (i.e., nausea, vomiting). “One interesting point about the study is that the 50 and 25 micrograms doses serve as kind of additional controls [as compared to just a placebo],” Barrow says. “I think it is as strong of a controlled study as you could possibly ask for. Observationally and clinically, it was very clear that 100 micrograms is the dose to take forward into our Phase 3 trial”

Rob Barrow, CEO of MindMed, explains the details of an End-of-Phase 2 (EOP2) meeting with the FDA.

THE MOVE TO A PHASE 3 TRIAL

During the EOP2 meeting, Barrow says MindMed was “in alignment” with the FDA on the core principles of what needed to get done for the Phase 3 trial and what the company needed to prove to submit its NDA. For that Phase 3, which will start sometime later this year, he says there obviously will be larger groups of participants, more sites, and even an international group that will include patients from other countries. But beyond that, the core elements of the trial design won’t change. “Everything we're doing in Phase 3 is an extension of what we did in Phase 2 because we have a high degree of confidence that we're going to see the same study design hopefully result in the same sort of outcomes in phase 3.”