
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 |
Approved | |||
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 & clinicaltrials.gov. |