Tactogen

If you want to listen to a clear, thoughtful, balanced and scientifically informed explanation of all the individual issues that arose during the recent #FDA ADCOM meeting for #MDMA, I highly recommend this #podcast. I agree with the analysis completely and learned some things. So thank you Matthew Baggott, PhD. I specifically appreciated the explanation of how the #public comments contributed to the outcome of this meeting and how Lykos Therapeutics will likely be able to work with the #FDA to develop appropriate #REMS. The message is hopeful. The obstacles are not insurmountable. The errors that were made in #studydesign and omissions of #data can be addressed. #Safety concerns can be mitigated. Issues on the role of #psychotherapy can be clarified. A great example of how to take the high road and learn from ALL voices, especially critical ones. There is a path forward for a new approach in #PTSD for #veterans and civilian #trauma survivors. 🙏 Delighted that new MDMA compounds are being developed by Tactogen and other #biotechs. We will not give up trying to address important #mentalhealth needs with #psychedelicdrugs. . thttps://lnkd.in/eD8yhiXx

Understanding the FDA MDMA Advisory Committee Meeting While most headlines have focused on the committee vote, I believe the key lessons of the AdComm meeting come from the FDA’s briefing document and presentation. FDA signaled continuing seriousness about applying standard drug development rules to evaluating MDMA and related drugs. This should leave us with optimism as it provides a clear path for the eventual approval of MDMA and other investigational medicines. It was not clear the AdComm meeting actually helped the Agency with their pending decisions. The committee lacked the time and resources to resolve the uncertainties about the data and thus were certain to vote no, despite what superficially, at least, looked like strong data. The overwhelmed, risk-averse stance of the committee could be seen in their explanations of their votes. For example, several members cited concern that prestudy MDMA exposure could create biases in participants, despite Lykos providing strong data that this was not an important predictor of outcomes. Members had seemingly stopped taking in and trusting numbers. As member Satish Iyengar, Ph.D., stated, “It’s actually strange to vote no when the p-value started with three zeroes, But there was just too many problems with it.” The Agency and broader discussion paid significant attention to trial design and unblinding. Yet we should note –as the FDA's Dr. Tiffany Farchione did– that the design Lykos used for their Phase 3 trials was largely finalized in 2017.  And crucially, because the Agency approved the trial design and officially agreed the endpoints could support a decision, the design limitations should be largely irrelevant to the August approval decision. Similarly, analyses of the durability of the therapeutic effect are “purely exploratory.” The meeting did make clear the Lykos NDA lacks some standard types of safety data. A large literature shows MDMA is generally well tolerated and can be used with adequate safety under medical supervision. However, FDA has limited ability to rely on the scientific literature and sponsors like Lykos are expected to collect safety data on their specific product.  Still, based on what we know from the literature, these open safety issues more represent box checking rather than true risks to the NDA. Yet checking the boxes will take time and it is plausible that Lykos may need one or more small studies and another submission cycle to do so. Despite the headlines, and no matter what response the FDA gives to Lykos in August, the FDA continues to behave fairly and predictably and I expect MDMA to be approved in a straightforward manner. If you want to dig deeper and ask questions, I will be participating in a free webinar about the Committee meeting and its implications, with our friends at Dragonfly44, on Wednesday, June 12th at 9:00am PST/12:00pm EST. https://lnkd.in/ggjD6gP5 Hope to see you there!

Understanding the FDA MDMA Advisory Committee Meeting While most headlines have focused on the committee vote, I believe the key lessons of the AdComm meeting come from the FDA’s briefing document and presentation. FDA signaled continuing seriousness about applying standard drug development rules to evaluating MDMA and related drugs. This should leave us with optimism as it provides a clear path for the eventual approval of MDMA and other investigational medicines. It was not clear the AdComm meeting actually helped the Agency with their pending decisions. The committee lacked the time and resources to resolve the uncertainties about the data and thus were certain to vote no, despite what superficially, at least, looked like strong data. The overwhelmed, risk-averse stance of the committee could be seen in their explanations of their votes. For example, several members cited concern that prestudy MDMA exposure could create biases in participants, despite Lykos providing strong data that this was not an important predictor of outcomes. Members had seemingly stopped taking in and trusting numbers. As member Satish Iyengar, Ph.D., stated, “It’s actually strange to vote no when the p-value started with three zeroes, But there was just too many problems with it.” The Agency and broader discussion paid significant attention to trial design and unblinding. Yet we should note –as the FDA's Dr. Tiffany Farchione did– that the design Lykos used for their Phase 3 trials was largely finalized in 2017.  And crucially, because the Agency approved the trial design and officially agreed the endpoints could support a decision, the design limitations should be largely irrelevant to the August approval decision. Similarly, analyses of the durability of the therapeutic effect are “purely exploratory.” The meeting did make clear the Lykos NDA lacks some standard types of safety data. A large literature shows MDMA is generally well tolerated and can be used with adequate safety under medical supervision. However, FDA has limited ability to rely on the scientific literature and sponsors like Lykos are expected to collect safety data on their specific product.  Still, based on what we know from the literature, these open safety issues more represent box checking rather than true risks to the NDA. Yet checking the boxes will take time and it is plausible that Lykos may need one or more small studies and another submission cycle to do so. Despite the headlines, and no matter what response the FDA gives to Lykos in August, the FDA continues to behave fairly and predictably and I expect MDMA to be approved in a straightforward manner. If you want to dig deeper and ask questions, I will be participating in a free webinar about the Committee meeting and its implications, with our friends at Dragonfly44, on Wednesday, June 12th at 9:00am PST/12:00pm EST. https://lnkd.in/ggjD6gP5 Hope to see you there!