Psychedelics And Treatment-Resistant Depression: Companies Weigh In On The Important Issue

(Part three of a four-part series)

Have a look at previous stories:

Psychedelics And Treatment-Resistant Depression: An Overview Of COMPASS' Latest Trial Outcomes

Psychedelics And Treatment-Resistant Depression: Reactions On Published Results

atai Life Sciences ATAI and COMPASS Pathways CMPS hold a strategic partnership, currently displayed in three advanced, yet "limited to equity interest," clinical trials under COMPASS' lead.

On the recent publication of the Phase 2 results, atai’s co-founder and CEO Florian Brand commented: “We couldn't be prouder of the team at COMPASS for their historic achievement. COMPASS was atai’s first psychedelic initiative, and we continue to be a supporter and largest investor in the company. We believe that the success of COMP360 will help pave the way for future therapeutics like those in atai's diversified pipeline.”

To further understand the trial’s potential repercussions, Benzinga spoke with Ronan Levy, lawyer and co-founder of Field Trip and partner at the cannabis and biotech VC fund Grassfed Ventures with extensive experience in both fields.

After the company’s recent split, Levy is now CEO of Field Trip Health & Wellness, the company that provides ketamine-assisted therapy for PTSD, depression, Generalized Anxiety Disorder (GAD) and trauma.

Levy says he's confident that the results of COMPASS’ trial present solid evidence for the further development and once-legal offering of psilocybin-assisted therapies for treating several mental health disorders. 

“I think it’s a very good foundation for a very controlled clinical trial, showing extremely positive results. It’s important to keep in mind that this is a single dose, with a limited degree of psychotherapeutic time, which compared to available alternatives of depression treatments some studies suggest 85% of people do not respond to, are still fabulous.”

Levy referred to another critical aspect of the results: the psychotherapeutic component involved. “I think increasingly more people are beginning to understand that when it comes to our mental health and well being, we shouldn’t think about it as isolating the brain and its neurochemistry from how we live our lives and the emotional processing that happens.”

As such, Field Trip’s CEO is certain that the larger psychotherapeutic support pairing the 2 psilocybin doses in the Phase 3 trials will substantially increase the Phase 2 trial's results. 

Regarding concerns about the study’s cases of suicidal ideation (SI,) Levy explained that the majority of them came from non-responders. 

“So for people who had larger doses and did not respond, SI was enhanced, because this population have already tried conventional treatments who may have had hope coming into this trial that they’d respond, whether they received placebo or the largest dose. If they don’t respond, then naturally that’s going to be that much more debilitating to their psyche to know that something that helps such a problem did not work. So it’s not surprising that SI may further occur,” he said.

He stressed the need to remember that treatment-resistant depression is among the most challenging issues to address and respond to. “It’s obviously terrible that SI is a result here, but it’s not entirely that surprising and may in fact be encouraging to other treatments because one of the things the study discusses is up to what degree it occurs in conventional treatments options, which I think is not insignificant as well.”

Costs & Future Regulations

Looking forward to COMPASS’ upcoming Phase 3 trials, having more therapist and clinician time will increase the cost of treatment, but Field Trip’s CEO believes looking at costs is the wrong metric. 

“I think we need to look at value across the board. Which is: if the results increase substantially, there’s a number of ways to consider the economic consequences of that. One is purely humanitarian considerations: if people feel better longer, then an increase in costs is not necessarily a negative thing, as long as the improvement increases more than the cost, then I think that is an improvement in efficiency.”

Levy exemplified his view with current results provided by Field Trip’s clinics. “After people complete from 4 to 6 ketamine-assisted therapy (KAP) sessions, their depression and anxiety scores typically go from severe to mild and those benefits last for months or longer. Which is a significant improvement. And it may go even longer than 4 months. We see these prolonged benefits with KAP, and I certainly anticipate that with period or episodic treatments of psilocybin-assisted therapy (PAT) we’re gonna see substantial improvements for people dealing with TRD and all other conditions.”

Though still being studied for its therapeutic effects, Levy believes econometrics still favor psilocybin-assisted therapy, especially over conventional treatment options. 

“Particularly when you weigh factors such as productivity, absenteeism, the fact that people suffering from depression tend to consume more medical resources... all of these considerations need to be put into the economic evaluation," he explained. "Simply because it’s more expensive because there’s more clinician time involved does not necessarily mean that is negatively more costly, and still, it’s likely to be significantly more value-driven than current treatment options by a long shot, whether that’s just therapy or SSRIs or conventional antidepressants or otherwise.”

In terms of safety concerns, REMS (Risk Evaluation and Mitigation Strategies) has not yet been negotiated between COMPASS and the FDA in an effort to mitigate the risks associated with psilocybin-assisted therapy. 

Nonetheless, Levy has held some conversations with MAPS on its REMS for MDMA-assisted therapy, based on which he anticipates that regulations are not going to be too restrictive, therefore limiting access, but ensuring that certain elemental safety considerations will be met.

For instance, treatment will most likely need to be done in clinic. Levy does expect there will be off-label uses of psilocybin, considering its safety profile, such as ketamine.

REMS will be a consideration for psilocybin yet not for ketamine. Nonetheless, Levy said that this has not led to a significantly negative outcome, just many theoretical concerns.

“Comparing REMS and ketamine clinics, I think the balance of need favors access: you have 25% of people around the world who are going to experience a clinically diagnosable mental health instance at some point in their lives. The need is significant, and the risks associated with psychedelics are actually quite low,” he said.

A Psychedelics Holistic Approach To Mental Health

Looking ahead, Benzinga asked if Field Trip would consider switching to treating patients with psilocybin or MDMA-assisted therapies, instead of ketamine therapy currently in use.

“My answer is it depends. Ketamine will probably still be the first option for a lot of people, because one of its advantages is that if you are taking SSRIs or conventional antidepressants you don’t have to be off them -such as happens with MDMA and psilocybin trials,- ketamine therapy can be started in conjunction with them,” Levy replied.

“The second reason is that ketamine treatment means people can be in and out of our clinics in 3 hours, so it’s a morning-afternoon. With psilocybin or MDMA, you’re usually looking at 4 to 10 hours that people have to be in-clinic, probably towards the upper end of that range; so it’s a much longer treatment, which means a harder schedule and harder to fit in a lifestyle.”

This is why, even if many people with MDD and TRD are interested in trying psilocybin, Levy believes ketamine will still be a part of the equation.

“What we expect to see in the future is that all these treatments options can create a holistic program aimed at enhancing the healing process, in such way that someone may come to a Field Trip clinic with TRD and because psilocybin will be the first psychedelic specifically approved for this condition, they may start with psilocybin-assisted therapy," he explained. "But then, the physician may say: ‘You know, I think if we unpack the treatment protocol, there’s a trauma underlying your depression, so MDMA-assisted therapy –maybe not specifically indicated and then off-label- will probably enhance your treatment regimen.’ And so, MDMA may be next in that person’s treatment protocol."

A person would not take ketamine directly after or jointly with the psilocybin dose, but a treatment protocol might start with one or two sessions of KAP, and then some weeks later do a psilocybin-assisted therapy session. 

“So I think people will cycle through a variety of assisted therapies over the treatment protocol. That’s what I expect will happen, and why I believe ketamine will remain as a highly relevant part of the treatment program for people,” Levy concluded.

Next up: Psychedelics And Treatment-Resistant Depression: COMPASS Replies To Comments
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