The late-stage biotech company addresses disease of the central nervous system (CNS) and announced efficacy results for 204 ‘new to treatment’ patients and safety results for all 627 patients from a phase 3 trial of REL-1017.
Patients treated daily with REL-1017 for up to one year experienced rapid, clinically meaningful, and sustained improvements in depressive symptoms and associated functional impairment. REL-1017 was well-tolerated with long-term dosing, showing low rates of adverse events and discontinuations due to adverse events. No new safety signals were detected.
Cedric O'Gorman, chief medical officer of Relmada, said: “These efficacy and safety results represent real-world potential outcomes for MDD patients when treated with REL-1017.
“The rapid and sustained therapeutic effects achieved with REL-1017 suggest the significant therapeutic potential of this promising late-stage product candidate as a mechanistically novel and differentiated treatment for MDD.
“The early magnitude and trajectory of clinical improvement remain consistent across all trials conducted to date. The long-term sustained clinical improvement, coupled with an extremely well-tolerated profile, adds to our enthusiasm for this agent as a potential therapeutic option for patients and prescribers.”
Study REL-1017-310 was a long-term, open-label, non-comparative, registrational phase 3 trial designed to evaluate the efficacy and safety of REL-1017 administered once-daily in patients with MDD for up to one year.
In total, 627 patients were enrolled, comprising 423 patients who rolled over (rollover patients/subjects) from placebo-controlled trials with REL-1017 and 204 ‘de novo’ patients who had not previously participated in trials with REL-1017.
Need to demonstrate efficacy in placebo-controlled trial
The trial was concluded when at least 300 patients had been treated for six months and approximately 100 patients had been treated for 12 months. At the time of study conclusion, 418 patients had reached at least six months of treatment, and 118 patients had reached at least 12 months of treatment.
Philippa Salter, Senior Neurology Analyst at GlobalData, added: “Whilst these positive results are important for Relmada Therapeutics in demonstrating the efficacy of REL-1017 as an adjunctive therapy for major depressive disorder (MDD), they have come in an open label trial.
“The drug will still need to demonstrate efficacy in a placebo-controlled trial, following a previous phase 3 trial where the primary endpoint was missed due to a high placebo response rate. Therefore, demonstrating efficacy compared to placebo in the two ongoing phase 3 trials due to complete in 2024, Reliance II and Relight, will be crucial to the prospects of REL-1017.
She added that there is a significant unmet need within the MDD market for pharmacotherapies that can demonstrate rapid antidepressant effect, an issue which REL-1017 is looking to address.
Combined with its sustained effects on depression symptoms, with just over 50% of patients achieving clinical remission at 12 months, she said REL-1017 has the potential to see strong uptake in the MDD market.
“In general, the side-effect burden is high with currently available antidepressants. By demonstrating favorable long-term tolerability with no significant weight gain or sexual dysfunction, the most undesirable side-effects of standard of care antidepressants highlighted by key opinion leaders interviewed by GlobalData, REL-1017 could be a more appealing long-term option to patients. This could help improve treatment compliance compared with other antidepressants, potentially boosting its overall efficacy” she said.
REL-1017, a new chemical entity (NCE) and novel NMDA receptor (NMDAR) channel blocker that preferentially targets hyperactive channels while maintaining physiological glutamatergic neurotransmission, is currently in late-stage development for the adjunctive treatment of major depressive disorder (MDD).
The ongoing clinical research program is designed to evaluate the potential for REL-1017 as a rapid-acting, oral, once-daily antidepressant treatment. In addition to the long-term, open-label study of REL-1017, the phase 3 development program for REL-1017 as an adjunctive treatment for MDD also includes the recently initiated Relight phase 3, randomized, double-blind, placebo-controlled trial and the ongoing Reliance 2 trial. Relight and Reliance 2 have the same key study design parameters.
Salter added: “However, if REL-1017 does enter the MDD market, it will face significant competition from Axsome Therapeutics’ Auvelity (dextromethorphan + bupropion), which was the first oral, rapidly acting antidepressant to be approved by the FDA in 2022.”