Eliem Therapeutics reported results from its Phase 2a clinical trial investigating ETX-810 for the treatment of diabetic peripheral neuropathic pain (DPNP), and provided an update on the status of the ETX-155 clinical program in epilepsy and depression. Update on ETX-810: ETX-810 is a novel, new chemical entity prodrug of the bioactive lipid palmitoylethanolamide (PEA) that is currently being evaluated in two Phase 2a clinical trials in subjects with DPNP and lumbosacral radicular pain (LSRP), commonly referred to as sciatica. In the Phase 2a clinical trial in DPNP, ETX-810 did not achieve statistically significant separation from placebo on the trial's primary endpoint, which assessed the change from baseline to week 4 in the weekly average of the daily pain score measured with the Pain Intensity Numerical Rating Scale (PI-NRS).

The multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial (NCT04688671) evaluated the efficacy and safety of ETX-810 in 159 subjects with DPNP over four weeks of dosing. 78 patients received 1,000 mg of ETX-810 twice daily, and 81 patients received placebo. ETX-810 was well tolerated in the study, with an encouraging safety profile.

However, the primary endpoint of the study was not achieved, and separation from placebo on the PI-NRS was not observed during the 4 weeks of dosing. The company has also fully enrolled its Phase 2a proof-of-concept trial evaluating ETX-810 in patients with LSRP (NCT04778592). The LSRP study has enrolled 149 patients and has a similar design to the Phase 2a DPNP study.

The LSRP study is expected to report topline data in the third quarter of 2022. Update on ETX-155: ETX-155 is a novel neuroactive steroid GABAA receptor positive allosteric modulator that the company plans to evaluate in subjects with major depressive disorder (MDD), perimenopausal depression (PMD), and epilepsy. ETX-155 is in an ongoing Phase 1b proof-of-concept trial in photosensitive epilepsy (PSE).

Last month, the company received clearance to proceed with an IND to progress ETX-155 in Phase 2a clinical trials in depression. Eliem has reviewed interim results from the Phase 1b PSE study and has elected to delay enrollment of its Phase 2a clinical trials of ETX-155 in major depressive disorder (MDD) and perimenopausal depression (PMD). Three patients have been evaluated to date in the Phase 1b PSE study, and the results of ETX-155 on the photoparoxysmal response observed following intermittent photic stimuli were inconclusive.

An analysis of the drug exposures in these patients indicated that drug levels were significantly lower than expected based on the pharmacokinetic profile observed in the two Phase 1 trials of ETX-155 in healthy subjects. The company is currently investigating potential root causes of the observed difference in exposure from the prior studies, including evaluation of any differences between the lots of drug product used in this study and those of the prior Phase 1 trials. The company will provide an update to timelines after the root cause is further investigated.