US FDA does not approve MDMA therapy for PTSD, requests more data

The MDMA-based therapeutic developed by Lykos Therapeutics, a California-based Public Benefit Corporation (PBC), has been reviewed and unapproved by the US FDA. The regulator has requested additional phase III trial data for further safety and efficacy information. 

The investigational MDMA therapeutic developed by Lykos was previously submitted to the FDA under the new drug application (NDA) designation in May 2024. However, the FDA Advisory Committee have since stated that the therapeutic cannot be approved due to concerns surrounding the manner in which the clinical trial was conducted. The Advisory Committee claims that there was a lack of documentation around whether trial participants abused the drug, as well as issues around the trial design. 

In a complete response letter (CRL) published by Lykos, the company have raised issues regarding the committee’s request. “The FDA request for another study is deeply disappointing,” commented Lykos CEO Amy Emerson. “While conducting another phase III study would take several years, we still maintain that many of the requests that had been previously discussed with the FDA and raised at the Advisory Committee meeting can be addressed with existing data, post-approval requirements, or through reference to the scientific literature.” Among the concerns raised by the FDA include collected endpoint data at 18 weeks, where draft guidance for psychedelic drugs indicates endpoint data to be collected at 12 weeks. Lykos had also previously aligned with the regulator in the Special Protocol Assessment in 2017 on a number of measures to reduce bias in the study design. For example, prior MDMA use among trial participants were not seen as detrimental, with almost 30% of participants in phase II studies reporting prior use of MDMA. These parameters were all shared with the FDA before establishing phase III trial inclusion and exclusion criteria under the Special Protocol Assessment established. 

Lykos have raised their own concerns regarding the Advisory Committee’s lack of subject matter experts on the panel, as well as the nature of their discussions which went beyond the scientific content in the briefing documents.  

The novel approach of psychedelic drug therapy in tandem with psychotherapy was raised as a concern by the committee as well. Some on the panel questioned whether the combination was necessary. While Lykos acknowledged the novel drug-therapy combined approach, the company stated that it will remain committed to developing this integrated approach. Emerson commented “Our heart breaks for the millions of military veterans, first responders, victims of sexual and domestic abuse, and countless others suffering from PTSD who may now face more years without access to new treatment options. We intend to work tirelessly and use all available regulatory pathways to find a reasonable and expeditious path forward for patients who deserve access to midomafetamine-assisted therapy for PTSD.” 

Source: 

Lykos Therapeutics Announces Complete Response Letter for Midomafetamine Capsules for PTSD [Accessed August 12, 2024] https://www.prnewswire.com/news-releases/lykos-therapeutics-announces-complete-response-letter-for-midomafetamine-capsules-for-ptsd-302219182.html