The Institute for Clinical and Economic Review said it cannot fairly judge Lykos Therapeutics’ MDMA-assisted therapy for post-traumatic stress disorder because of concerns about certain elements of its clinical trials.
The drug pricing watchdog said some trial participants already had preconceptions about psychedelics and that the trials may not have been effectively blinded, which makes it difficult to evaluate the treatment’s risk-benefit profile.
These comments come before Lykos’ PTSD candidate is set to face an FDA advisory committee on June 4, which will weigh the treatment’s risks and benefits prior to an August 11 PDUFA date. The adcomm will be the first to discuss a potential new PTSD therapy in 25 years.
According to ICER’s draft report published Tuesday, several issues could obscure the validity of Lykos’ MDMA-AP studies. First, some therapists and patients involved in the trials already had “strong prior beliefs about the value of psychedelics” for mental health conditions. Around 40% of the patients had prior experience with MDMA.
Second, patients were able to identify when they had received MDMA therapy due to its psychedelic effects, meaning the studies were “functionally unblinded.” ICER added that therapists were also likely able to identify who had received the drug, “given their experience with psychedelic medications.”
In addition, ICER noted concerns that therapists encouraged patients to provide “favorable reports” and “discouraged negative reports.” With these observations, ICER ultimately concluded that it is “not able to assess” the risk-benefit profile of MDMA-AP.
There were some counterpoints in an ICER public comment folio published last month. According to a letter signed by therapists involved in Lykos’ Phase 3 studies, functional unblinding is not just an issue in psychedelic research but can affect clinical research more broadly.
The therapists added that Lykos’ Phase 3 trials of MDMA-AP “used independent raters blind to the participant’s treatment” for primary outcome assessment to help mitigate the effects of functional unblinding.
But Otsuka Pharmaceuticals, another biotech with its own candidates in PTSD, echoed ICER’s concerns on Lykos’ studies. Otsuka said in the folio that participants’ preconceived notions on psychedelics and the potential pressure to suppress negative experiences were “concerning” and “may have skewed” the results of Lykos’ trials.
Last month, Otsuka and partner Lundbeck filed an sNDA for their PTSD candidate, which is a combination of brexpiprazole and sertraline.
PTSD affects more than 13 million adults in the US, with patients experiencing symptoms for more than six years on average, Lykos said in the folio. Currently available medications treat individual symptoms but do not address the root of the condition.