Psychedelic treatments on cusp of approval, but questions remain

There is a new wave of psychedelic treatment moving through clinical trials targeting mental health conditions, and they are showing strong efficacy. Ben Hargreaves finds that certain treatments are being discussed for approval, but difficult questions remain on how to regulate them.

Mental health conditions are becoming better understood, as the stigma and silence that often marked such illnesses in the past has begun to dissipate. Depression is one of the most common health conditions globally, with an estimated 2-6% of people experiencing the condition each year. Overall, the WHO estimates that one in eight people in the world live with a mental disorder.

According to PhRMA, in 2023 there were 160 medicines in development for all mental illnesses. In the same report, the industry lobby also noted that having a serious mental illness reduces average life expectancy by 10-20 years. The need for new, effective treatments for mental health conditions is pressing. However, 160 drug candidates cannot be viewed as a healthy pipeline, as the associated clinical failure rate means 10% or fewer might make it through to commercialisation.

This is why there is a degree of excitement about a new wave of treatments targeting mental health conditions. The challenge and controversy over these drug candidates is that they are developed using compounds that are associated with illicit drugs. The potential new treatments are based on drugs, such as MDMA, psilocybin, and LSD. This poses interesting questions for regulators and drug enforcement agencies should these compounds continue to show efficacy in trials

The new wave

The research into the use of certain ‘recreational drugs’ for use as treatments has exploded in recent years, with studies emerging from both academia and companies showing positive results. In 2023, a University of California San Francisco (UCSF)-led study looked into the potential for MDMA to treat people living with post-traumatic stress disorder (PTSD). The phase 3 results showed that the drug was able to outperform the placebo treatment, with 71.2% of study participants in the MDMA-assisted therapy group no longer meeting the diagnostic criteria for PTSD. By comparison, only 47.6% of the patients on placebo treatment managed the same. Lykos Therapeutics is developing the treatment and the company announced that the FDA had provided a priority review of its new drug application for the indication of MDMA-assisted therapy for PTSD.

Compass Pathways is another company moving an asset through its pipeline, but for the indication of treatment-resistant depression. Its most advanced treatment candidate is COMP360, for which the biotech announced the initiation of a global phase 3 study in 2023. The phase 3 trial will be the largest randomised, controlled, double-blind psilocybin treatment conducted, following positive results from a phase 2b trial. In the latter trial, 29.1% of patients receiving a 25mg dose were in remission at week three, and 20.3% of patients had a sustained response at week 12.

Another notable event for the field occurred in March 2024, as MindMed received breakthrough designation from the FDA for its MM120 (lysergide d-tartrate) potential therapy. The drug is a synthetic ergotamine belonging to the group of classic, or serotonergic, psychedelics. MindMed is exploring the drug as a treatment for generalised anxiety disorder (GAD). In phase 2b trials, MM120 met its key secondary endpoint at 12 weeks with a 65% clinical response rate and 48% clinical remission rate.

Daniel Karlin, chief medical officer of MindMed, discussed further details of the treatment candidate with pharmaphorum, as well as its potential improvement on existing therapy options. Karlin stated: “Data from our phase 2b study demonstrated a single oral dose of MM120 in patients with GAD resulted in a rapid and durable clinical response through 12 weeks without the need for additional psychotherapeutic intervention beyond the study drug.”

“The percentage of patients experiencing meaningful clinical improvements was more than double the current standard of care in this phase 2b study,” he continued. “And, while it was not the study’s primary purpose, results […] showed MM120 also showed rapid and robust improvement on depression symptoms – a common comorbid indication with GAD.”

A question of regulation

With clinical trial results pointing towards selected potential treatments being effective enough for approval, the next question is how regulators and national authorities will react to the drug applications. The US Drug Enforcement Agency (DEA) currently has the compounds behind each treatment mentioned listed as Schedule I substances, meaning that they are considered to have a high potential for abuse, with no accepted medical use, and ‘a lack of accepted safety for use under medical supervision’.

However, there have been previous cases where companies have managed to receive approval for treatments that are considered illicit drugs. One example is Johnson & Johnson’s Spravato (esketamine), which has been approved for treatment-resistant depression, even though it is produced from ketamine. Similarly, Jazz Pharma acquired GW Pharma for $7.2 billion based on the latter’s successful commercialisation of a cannabis-derived treatment for childhood epilepsy.

Karlin noted that, for MindMed, the breakthrough designation provided by the FDA meant that there would be ‘more frequent interactions’ to ensure the regulator and the company are ‘in lockstep agreement’ as the regulatory process moves forward.

The agency itself issued a press release in June 2023 to issue draft guidance for those companies looking to research the use of psychedelic treatments. The FDA acknowledged the ‘growing interest’ in the area, particularly for use in the treatment of mental health conditions. Tiffany Farchione, director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research, stated: “By publishing this draft guidance, the FDA hopes to outline the challenges inherent in designing psychedelic drug development programmes and provide information on how to address these challenges. The goal is to help researchers design studies that will yield interpretable results that will be capable of supporting future drug applications.”

With Lykos Therapeutics having already filed for approval of its treatment, the rest of the field could soon be given an indicator of where the regulator stands on such therapies – the company has an expected decision date of 11th August. An approval would mark a first for a psychedelic-assisted therapy. However, there are still questions over the prescription of the therapy, and how this would be managed. On a business level, it would also be a test case for how financially viable a treatment is when it has to be delivered alongside psychotherapy and other support services. With the number of such therapies growing in the pipeline, it appears more a matter of when these questions will be answered.