Pomaglumetad
A medicine that reduces glutamate release through mGlu2/3 receptors. Eli Lilly stopped its development in 2012; a small trial in young people began in Australia in 2026.
At a glance
- Type
- Medicine: mGlu2/3 receptor agonist
- Used for
- Tested in schizophrenia; now in young people with early psychosis
- Status
- Experimental, phase 3 trials found no benefit in 2012; a small trial began in Australia in 2026
- Administration
- Tablets, twice a day
Clinical summaryFor health professionals
- Phase 2 (Patil 2007): better than placebo at week 4, without raised prolactin, movement side effects or weight gain.
- Downing 2014: 1,013 patients, 6 weeks, 40 or 80 mg twice a day; neither dose beat placebo, risperidone did.
- Adams 2014: 678 patients, 24 weeks against aripiprazole; less weight gain, smaller PANSS improvement (12.0 against 15.6 points), more serious adverse events (8.2% against 3.1%).
- Lilly stopped development in August 2012 after a futility analysis, not for safety. Meta-analysis of 10 trials, 3,715 patients: no efficacy, more dropouts for adverse events (Mishra 2026).
- Orygen, Melbourne (2026): open-label feasibility trial, 40 mg twice a day for 12 weeks, ages 18 to 25, first-episode psychosis with insufficient response to one antipsychotic, or clinical high risk (Denovo 2026).
What it is
Pomaglumetad activates mGlu2 and mGlu3 receptors, which act as brakes on glutamate release. It was designed to calm the excess glutamate activity thought to drive some symptoms of schizophrenia, without acting on dopamine.1
History
In 2007, a trial published in Nature Medicine found it better than placebo after four weeks, without the raised prolactin, movement problems or weight gain associated with antipsychotics.1
How well it works
Later trials did not confirm the result. In a trial of 1,013 people over six weeks, neither dose did better than placebo, while the antipsychotic risperidone did.2 Against aripiprazole over 24 weeks, in 678 people, pomaglumetad caused less weight gain but improved symptoms less, and serious adverse events were more common.3 Added to antipsychotics for negative symptoms, it did no better than placebo.4
In August 2012, Eli Lilly stopped its development after an independent analysis concluded that the second main trial was unlikely to succeed. The decision was not based on safety.5 Pooled across 10 trials with 3,715 people, pomaglumetad did not work, and people stopped it more often because of side effects.6
Denovo Biopharma, which licensed it from Lilly, reports that people early in their illness improved more than the rest. In 2026, it announced a small open trial at Orygen in Melbourne, in people aged 18 to 25 whose first episode of psychosis has not responded well enough to a first antipsychotic, or who are at high risk of psychosis.7
Alternatives
Evenamide (opens in a new tab) also reduces glutamate release, by a different route, and is in phase 3 trials.
What we don’t know yet
- Whether people early in their illness benefit, as the Melbourne trial is testing.
