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Reunion Neuroscience has reported a mid-stage success with its short-acting psychedelic drug in postpartum depression (PPD), paving the way for the company to initiate a registrational trial next year. The biotech’s candidate, known as RE104, met the primary endpoint of change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at seven days in a Phase 2 trial called RECONNECT. The drug given at 30 mg produced a 23-point MADRS reduction versus a 17.2-point reduction for the active control arm, which translates to a p-value of 0.0094. Participants in the control arm received a 1.5 mg dose of RE104. Using a subtherapeutic dose of a drug as control is a common strategy in psychedelic trials, because opting for a traditional placebo can result in what’s known as functional unblinding and expectation bias. The Phase 2 study enrolled 84 adults with moderate to severe PPD, according to a Monday release. RE104 is a short-acting prodrug of a psychedelic compound called 4-OH-DiPT, which is similar to psilocybin. It is given as a single dose without psychotherapy and most patients are ready for discharge within four hours of injection, Reunion said. The biotech plans to advance RE104 into a Phase 3 PPD study in 2026. The Phase 3 will likely need to include a standard placebo arm and potentially a third arm that contains an active but lower dose of RE104, Reunion’s chief medical officer Mark Pollack told Endpoints News in an interview. Current treatments for PPD are “slow-acting and burdensome,” lead investigator Anita Clayton said in the release. Sage and Biogen’s Zurzuvae secured FDA approval for the condition in 2023 based on data from a pair of Phase 3 studies which showed it improved symptoms as early as three days. Before Zurzuvae, patients only had access to treatments that took several weeks to work. RE104 achieved “clinically meaningful reductions” in MADRS as soon as the first day after administration in the Phase 2 study, according to Reunion. Just over 70% of patients in the treatment arm were in remission at seven days compared with 41% of patients in the active control group. Remission rates in most depression trials are “maybe half or even a third” of what RE104 achieved in the mid-stage trial, Pollack said. “So to see that kind of rapid movement of patients [in the study] into remission is unusual” in a positive way, he said. The drug is also in development for adjustment disorder related to cancer and other medical illnesses, with a Phase 2 trial due to start in the third quarter. Reunion was a publicly traded company, but was taken private in 2023 by the investment firm MPM BioImpact. The biotech secured $103 million in a Series A raise last year that was supported by MPM and Novo Holdings, among others. The cash should fund its activities through 2027. Reunion said it is fully prepared to potentially launch and commercialize RE104 by itself. Editor’s note: This article was updated throughout with interview comments from Reunion.

A small, New Jersey-based drug developer plans to push an experimental psychedelic compound into late-stage testing now that its scored positive results in a postpartum depression study.That study enrolled 84 women with moderate to severe postpartum depression, each of whom received a single injection of Reunion Neurosciences RE104 and were then monitored for four weeks. Participants were split into two groups. One got the full, 30 mg dose of RE104, while the other got a far lower dose and served as an active control arm.According to Reunion, the trial achieved its main goal as the 30 mg group showed significantly greater reductions on a widely used depression scale where lower scores indicate less severe symptoms. Seven days after treatment, scores in the experimental arm had fallen by 23 points, versus 17.2 points in the active control arm.Reunion said researchers also saw clinically meaningful responses in the higher dose group that started the day they received their injections and lasted through the 28-day follow up. Just over 77% had scores that improved by 50% or more one week after treatment. In the control arm, 62% hit that milestone. Between the two groups, 71% of the former achieved remission of their depression symptoms at Day 7, compared to 41% in the latter.Reunion said its drug which functions similar to psilocybin, a molecule found in some psychedelic mushroom species was well tolerated by patients. There were no serious adverse events, nor was there any treatment-emergent treatment-emergent seizures or suicidal ideation or behavior.Anita Clayton, the trials lead investigator and the chair of psychiatry and neurobehavioral sciences at the University of Virginia School of Medicine, called the findings promising in a Monday statement from Reunion. She noted how postpartum depression affects roughly 15% of new mothers within a year of them giving birth. It is still the most common complication of pregnancy and childbirth in the U.S., with nearly 500,000 women diagnosed annually.The only medicines approved specifically for PPD are Zurzuvae and Zulresso, both of which were developed by Sage Therapeutics. Sage stopped marketing Zulresso last year, though, and sales of Zurzuvae haven't grown quickly.Despite its prevalence and severity, current treatment options for PPD remain limited and are often slow-acting and burdensome, leaving many new mothers without timely, effective care, Clayton said in a statement. I look forward to the continued evaluation of RE104 in a Phase 3 trial and believe it could represent a significant shift in the treatment of maternal mental health disorders.Reunion also disclosed on Monday preliminary results from a clinical lactation study, wherein the level of metabolites in participants breastmilk was less than 0.1% of the 30mg RE104 they received. Thats an order of magnitude below the level that might potentially cause risk to the infant, according to Reunion, which believes these results suggest that mothers who wish to return to breastfeeding following RE104 treatment may be able to do so with limited interruption.Based on the favorable data collected thus far, Reunion intends to push its drug into a Phase 3 trial that should begin next year and could tee up an approval application for postpartum depression. The company also wants to start, on the back end of 2026, a Phase 2 study focused on people with adjustment disorder related to cancer and other medical illnesses.Reunion formed through a few years ago through the split of a predecessor company, Field Trip Health. It then went private in 2023 after agreeing to sell to MPM Capital in an all-cash deal that valued Reunion at roughly $13 million.In the spring of 2024, MPM co-led a $103 million financing round for Reunion that drew investment from half a dozen other backers, including Novo Holdings, the parent company of Ozempic-maker Novo Nordisk. '