Relmada blames placebo for its depression woes

In REL-1017, Relmada Therapeutics had hoped it had an oral NDMA receptor blocker that could stop depression without the mind-altering side effects of other drugs in this class, such as ketamine. Those hopes are now in tatters after the group’s sole project flunked its first phase 3 trial, Reliance III. Relmada, whose stock plunged 79% this morning, blamed a high placebo response and noted that at some study sites placebo outperformed REL-1017 on the primary endpoint, the Montgomery-Asberg depression rating scale. The company pointed to a post-hoc analysis that excluded sites with “implausibly high or low placebo responses”, but the result cannot bode well for the rest of the pivotal programme; two adjunctive pivotal trials are also set to read out this year. Investors saw Relmada’s pain as Axsome’s gain – the latter got approval in August for its oral drug Auvelity, which acts on the NMDA receptor among other things. Axsome opened up 7% today. Johnson & Johnson’s Spravato is another marketed NMDA blocker, but is inhaled, and can only be given under supervision in a healthcare setting because of the risk of side effects and potential for abuse.  

Selected NMDA receptor antagonists in development for depression
Project Company Description Note
Spravato Johnson & Johnson Esketamine nasal spray Restricted distribution programme owing to side effects & abuse potential
Auvelity Axsome Therapeutics Oral dextromethorphan hydrobromide + bupropion hydrochloride* Launch set for early Q4 2022
Phase 3
REL-1017 Relmada Therapeutics Oral methadone enantiomer Failed ph3 monotherapy trial, Reliance III, Oct 2022; adjunctive Reliance I & II to read out H2 2022
Phase 2
CLE-100 Clexio Biosciences Oral esketamine Cleo completes Oct 2022
PCN-101  Atai Life Sciences/ Perception Neuroscience Infused ketamine enantiomer  NCT05414422 completes Nov 2022
SLS-002 Seelos Therapeutics Intranasal racemic ketamine NCT04669665 completes Dec 2022
Phase 1
AV-101 Vistagen Therapeutics Oral prodrug of 7-chloro-kynurenic acid Failed ph2 Elevate in MDD in 2019; now in ph1 + probenecid with view to development in "several distinct neurological disorders"
*Dextromethorphan is NMDA receptor antagonist & sigma-1 receptor agonist. Source: Evaluate Pharma &

Share This Article