Activists are not necessarily drug developers - my opinion on the FDA Advisory Committee hearing on MDMA

This week'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.

This week'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:

1. 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).
2. 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.
3. 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!)
4. This week'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].
5. 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].
6. 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].
7. ?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.dhirubhai.net/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