Activists are not necessarily drug developers
My opinion on the FDA Advisory Committee hearing on MDMA and what it means for atai
Yesterday’s FDA Advisory Committee hearing and subsequent two votes AGAINST Lykos Therapeutics’ (formerly known as MAPS public benefit corporation) MDMA assisted therapy (MDMA-AT) for the treatment of PTSD has been a sobering day for everyone who believed that activists and non-profits could be (better) drug developers for late-stage clinical trials. This episode has demonstrated that they are not.
While there have been positive examples of activists/non-profits who have developed groundbreaking drugs early-stage, they have seemingly only been successful when handing over to biotech or pharma companies to push them through the lates stages and commercialization.
Yesterday’s negative outcome has obviously been disappointing for all of us, as we (still) believe MDMA (which is not itself a psychedelic in the core definition, more below) is a promising drug with tremendous therapeutic potential for patients with severe mental health issues.
And to make it crystal clear: It isn’t MDMA itself that was rejected per se, but the specific, poor data set provided by Lykos Therapeutics; in my opinion, there is still a strong chance that MDMA, with a properly conducted clinical Phase 3 trial program that addresses those concerns of the FDA advisory committee, will get approved.
I also want to emphasize that this is a non-binding vote from an FDA public advisory committee and not the FDA’s ultimate decision on Lykos’ NDA, which is expected by August 11. The FDA, which has historically appeared very supportive of exploring the therapeutic potential of psychedelics as evidenced by multiple Breakthrough Therapy Designations for psychedelic compounds over the last 10 years, has the prerogative to make an approval decision at odds to the advisory committee’s vote, though that is unusual.
But again, even if the FDA follows yesterday’s recommendation, this is not a NO to MDMA for good, but just for this particular trial package and broader data set. The committee particularly cited discrepancies in clinical trial design and conduct, inadequate collection of safety and other relevant data, bias in the evaluation of patients, and cases of patient abuse during the trials.
Or in short: The trials of MAPS/Lykos have been deemed chaotic, with nonstandard designs - particularly regarding therapy - and questionable execution. IMO their Phase 3 trials more closely resemble traditional phase 2a trials in terms of size and quality.
New trials can overcome the shortcomings of this package and potentially result in ultimate approval.
It is also worth highlighting here that the first “psychedelic drug”, Spravato by Johnson & Johnson, has already been approved a while ago, showcasing that the challenges MDMA and other psychedelics face can be successfully overcome. Spravato, which is an esketamine nasal spray, faced similar hurdles as MDMA such as successful blinding, abuse liability studies, and rigorous clinical trials. The approval of Spravato provides a clear blueprint for how MDMA and psychedelics can navigate the complex regulatory landscape if executed properly.
Most importantly, imho, yesterday’s events underscore the importance of atai Life Sciences’ mission: Proving once and for all that with rigorous clinical trials, psychedelics and MDMA have a place in modern medicine and can support the many millions of people in need of better mental health treatments.
atai can afford to conduct those large-scale clinical trials that address all the questions that the regulatory bodies such as the FDA want to see answered (see an overview here[1]) as a result of our diligent approach to building a strong patent portfolio, an approach for which MAPS and their supporters have criticized and ostracized us. This “traditional” approach enabled atai to raise hundreds of millions of dollars to hire an experienced team that is capable of designing and executing the required studies to optimize the chances for success.
Yesterday’s events also demonstrate the special responsibility placed on anyone working with psychedelics and MDMA. Given the vast anecdotal evidence – often first-hand positive experiences witnessed in patients seeking help in those substances – there is a risk of becoming overconfident, zealous, and self-righteous. The psychedelic drug development industry must acknowledge that a vast majority of people – including many researchers and people sitting on boards like yesterday’s AdCom meeting – have not tried those substances themselves or witnessed somebody who has been helped by them. We cannot sway them with stories or advocacy. The only way to convince them is with strong data – which has been the focus of atai’s approach from day one.
Here’s my opinion what this all means for atai and the psychedelic renaissance:
MDMA is considered an entactogen, NOT a psychedelic. It is often grouped together with psychedelics as it shares both mind altering effects and a similar past with some psychedelics: a once medical drug which became illegal and stigmatized, and now is about to makes its way back (and still will, hopefully).
Both classic psychedelics and MDMA have risks (just like any medical drug has risks, nothing comes without risks; look at the science on Aspirin for example). However, MDMA’s risk profile is considered more concerning than the ones of many psychedelics because of its amphetamine-like properties which can result in cardiovascular effects, serotonin syndrome, teeth grinding, hyperthermia, and dependence when taken repeatedly. Regardless, I believe those risks are manageable when they are properly researched, understood, and characterized. Yesterday’s hearing showed that more work needs to be done to properly characterize and address those risks.
I have always believed that atai would have to be overly rigorous with the design and execution of all its clinical trials. Fair or not, people will look at psychedelics and MDMA more critically, and with more scrutiny, than they would apply to a ‘typical’ drug. This is why atai and Compass have always strived to do much more than technically needed and required. For example, Compass’ TWO Phase 3 trials have more than 800 (!) participants in total, compared to just 200 in total for the Lykos/MAPS Phase 3 (which was smaller than Compass phase 2b!)
Yesterday’s disaster is also a critical tale of capitalists who might be (secretly) ashamed of their financial success and hence anchored on one topic – MDMA and psychedelics – and denounced capitalism in relation to those substances.
Drunk on virtue signaling, those MAPS supporters have done a huge disservice to the MDMA and psychedelic renaissance.
Read more here why I believe capitalism is the best system we have, especially for drug development, including psychedelics[2].
Even if the original / racemic MDMA does not recover from this setback (although I hope it does with more and better studies), atai has a new, potentially better and patent-protected version of MDMA in its pipeline (as we had foreseen the problems that now became obvious), which in early trials has demonstrated a much better initial safety profile[3].
And MDMA is not the only hope for patients suffering from PTSD. Compass Pathways recently generated very encouraging data for the use of psilocybin for PTSD[4].
Please find my full view on atai and its extensive pipeline here[5].
I am proud of atai and Compass and their role as the flag bearers for psychedelics, and (in atai’s case) now also for MDMA. I am aware of the huge responsibility now weighing on us, and I am confident atai and Compass will not disappoint.
[1] https://atai.life/programs/
[2] https://www.linkedin.com/pulse/open-letter-tim-ferriss-value-patents-psychedelic-angermayer/
[3] https://atai.gcs-web.com/news-releases/news-release-details/atai-life-sciences-announces-positive-topline-results-single/
[4] https://www.fiercebiotech.com/biotech/compass-tracks-ptsd-improvements-psilocybin-therapy-sails-midphase-data-drop
[5] https://christianangermayer.substack.com/p/atai-life-sciences
Rick Doblin was arrogant and dismissal of his critics that pointed out legitimate issues during the trial. His attempt to parade veterans at the open FDA committee was an obviously PR stunt. Over and over again, we were reminded that “30 veterans die every day of suicide” as if that appeal, in and of itself was going to be enough to convince the FDA. MAPS was so naive about the drug approval process. As I know someone who works in the industry, it’s clear that MAPS knew little to nothing about submission process. They should have hired a CRO much earlier. They needed to have a quality and regulatory person on board earlier. They shouldn’t try to hide adverse effects as the FDA frowns on that kind of behavior. MAPS didn’t have their act together, but then tried to lay the blame at rogue ‘anti capitalist’ critics which is quite laughable. All their sycophants including Robin Carthart Harris came back with that same whiny complaint, the unpatriotic anti-capitalists who don’t like veterans did them in. No. That’s not true. Their own hubris, their own inability to take feedback, their naivety about the FDA submissions process and what it means to start up a biotech or pharmaceutical company is what did them in.
They all signed a letter (including site investigators associated with UCSF, Polaris and Sage Integrative) appealing to FDA to change their mind. Surely, the FDA made a big mistake. No. The FDA did not make big mistake as their primary mandate is PATIENT SAFETY. Why should the FDA be swayed by a bunch of site investigators who were primarily opportunistic, not experienced seasoned trauma informed professionals to be taken seriously. These clinics offer crappy psychotherapy services for ketamine as their psychotherapists know little to nothing about PTSD. These people, who are more concerned with social justice and getting pronouns correct than understanding primary trauma interventions, are going to roll out future MDMA services? I don’t think so. If you want to offer something to help people with PTSD, your psychotherapists should be experienced, licensed and able to offer the latest neuroscience based techniques for integration. “Hippy, trippy become a psychedelic therapist with 150 hours of training” and all the client needs I do is — “trust your inner healer” is total bullshit! And that’s the bogus, non scientific psychotherapy intervention that Mithoefer used to train scores of psychotherapists (trust whatever your intuition says, whstever you feel like doing in the moment) it was offered to FDA. Really? The FDA wouldn’t be able to see through that?
Asking the FDA to approve a non evidenced based psychotherapeutic intervention was a huge mistake. Mithoefer who stated he didn’t care if his malpractice attorney was disapproving of his practice of rolling around on the ground with his female patient while they’re taking psychedelics. (See: @https://substack.com/home/post/p-149470666 )People at MAPS — a real bunch of ethical folks! Can’t imagine how this laissez faire attitude regarding a patient’s heightened state of vulnerability and what ethical precautions and guidelines needs to be implemented in a regulated environment with licensed mental health professionals subject to malpractice would translate. It was a big mistake for MAPS not to be proactive address ethical and clinical trial issues earlier because it just ended up biting them in the ass in the end.
I had planned to participate in the trial as I am a survivor with complex PTSD history. Glad I never did. Ketamine has worked for me because I found a stellar provider with proper experience and expertise. Maybe psilocybin would work as well for me. MDMA isn’t the only game in town. Never good to put all your eggs in one basket. As an investor or a consumer of mental health services, one shoukd always be mindful of what will offer the best return on investment.