The new γ-aminobutyric acid type B (GABAB) agonist lesogaberan reduces transient lower esophageal sphincter (LES) relaxations and reflux episodes in patients who have persistent GERD despite concomitant PPI therapy, report Guy Boeckxstaens (University Hospital Leuven, Belgium) and colleagues.

The transient LES relaxations associated with reflux are mediated by a vasovagal reflex pathway, but known GABAB agonists (such as baclofen) that target this pathway at several points are linked with adverse effects in the CNS. Lesogaberan, however, “seems to be safe and devoid of these effects,” notes Boeckxstaens.

This randomized, placebo-controlled crossover study included 27 patients with GERD who had reflux symptoms despite PPI treatment. The participants received either 65 mg lesogaberan or placebo twice on day 1 and once on day 2. After 5–28 days, the patients crossed over to the opposite treatment.

Patients given lesogaberan had 35% fewer reflux events on day 1, 25% fewer transient LES relaxations on day 2, and 28% higher mean LES pressures than did those who received placebo. Adverse events were similar in both groups.

Lesogaberan had a greater effect on reflux episodes than on transient LES relaxations, which indicates that the drug inhibits reflux via several mechanisms. The researchers suggest that the moderately increased LES pressures associated with lesogaberan therapy could prevent reflux events associated with high intra-abdominal pressure and low resting LES pressure, as well as those caused by LES relaxation. The researchers also speculate that GABAB agonists potentiate the effects of PPIs or directly affect acid secretion.

“Phase II studies are ongoing in patients with GERD despite PPI treatment, which will hopefully result in registration of the drug,” concludes Boeckxstaens.