The Compass Points to Approval

The FDA’s 2024 rejection of MDMA-assisted psychotherapy for treating PTSD cooled the exuberance surrounding psychedelic research—but things are starting to heat up again. Guy Goodwin, M.D., D.Phil., chief medical officer at Compass Pathways, provided some of the latest data from the company’s two Phase 3 trials of its psilocybin formulation Comp360.

In COMP005, individuals who received one 25mg dose of psilocybin experienced dramatic reductions in depressive symptoms (assessed with the Montgomery-Asberg Depression Rating Scale) after just two days relative to those receiving inert placebo (mean difference of 4.7 points), with the difference remaining significant after six weeks (mean difference 3.6 points). Similar results were seen in the COMP006 study, in which the placebo group received a 1mg dose of psilocybin (mean MADRS difference of 3.0 points at six weeks).

Goodwin pointed out that a key facet of the psilocybin dosing session is that it’s mostly an introspective experience—there is minimal interaction between the patient and therapist. One of the reasons the FDA rejected MDMA-assisted therapy was the uncertainty of how strong the psychotherapy component of treatment was. Goodwin concluded by saying that Compass hopes to submit its New Drug Application for Comp360 by the end of the year.

Bridging the Day-Night Gap

Narcolepsy is a rare condition, but it’s likely that many patients with this underdiagnosed disorder will end up in psychiatric offices due to related symptoms, said Anne Marie Morse, D.O., director of the pediatric sleep medicine and child neurology programs at Geisinger Medical Center. So, it’s not quite like finding a needle in a haystack, she said. “It’s more like a needle in a needle stack.”

There may soon be a new treatment for that needle in the form of oveporexton (TAK-861, from Takeda), based on promising findings from two Phase 3 trials: First Light and Radiant Light. After 12 weeks, individuals taking oveporexton 2mg twice daily showed significantly improved wakefulness and sleep latency relative to placebo; more than half of participants taking oveporexton reduced their sleep latency by over 20 minutes. (The First Light study included a 1mg twice-daily dose that was also effective.) Side effects were also generally mild and transient, with no issues related to blood pressure or hepatotoxicity.

Importantly, the medication improved quality-of-life measures often described as important by patients, such as self-reported vitality and the ability to perform activities. “They would love to be able to go out to dinner or just watch a movie,” Morse said. “The things that we take for granted every single day.”

Olanzapine/Samodorphan in the Real World

Olanzapine is one of the most effective antipsychotics, but it comes with some of the highest metabolic risks. The approval of Lybalvi (olanzapine plus the opioid antagonist samidorphan) was designed to keep the efficacy but lose the weight. The clinical trial data were impressive—but how has this combo medication fared with real-world patients?

Andrew Cutler, M.D., clinical professor of psychiatry at SUNY Upstate Medical University and chief medical officer for the Neuroscience Education Institute, discussed findings gleaned from a large insurance database (Komodo), which showed the efficacy is legit. On average, in the 12 months after initiating olanzapine/samidorphan, individuals with schizophrenia or bipolar disorder experienced 24% and 42% fewer hospitalizations, respectively, than the 12 months prior to initiation—with the greatest benefits seem among young adults ages 18 to 34. Similar findings were seen with emergency department visits, whereas outpatient visits remained stable, showing that the patients were still engaging in their care.

Compared with adults taking olanzapine alone, those on olanzapine/samidorphan were about twice as likely to be adherent after 12 months; they also demonstrated longer periods of drug persistence (days of continuous use). Cutler said that the latter data point is pertinent. A patient is considered adherent if they take at least 80% of their prescribed medication, he said, “but there's actually data now [showing] that if you miss only 20% of your pills, your risk of relapse goes up.” ■