A recent study depicted that in Japanese patients with non-erosive reflux disease (NERD), 10 mg vonoprazan monotherapy did not demonstrate superiority to placebo with respect to the proportion of days without heartburn in the full analysis set. However, the per-protocol-set sensitivity analysis illustrated that vonoprazan was well tolerated, depicted a remarkable improvement of symptoms, delivered rapid relief from heartburn symptoms and had a considerably higher cumulative rate of heartburn resolution. 

As per study authors, the heterogeneous pathophysiology of NERD might explain the partial response of vonoprazan therapy.  A phase 3, randomized, multicenter, double-blind, placebo-controlled study was conducted  to investigate the safety and efficacy of 10 mg vonoprazan on heartburn symptoms in Japanese patients (aged 20 years and older) with NERD and recurrent heartburn.

Participants were either allocated to placebo (n = 245) group or once-daily 10 mg vonoprazan (n = 238) group for four weeks. The frequency of heartburn experienced by patients during the four week treatment period (estimated by the proportion of days without heartburn) was the primary outcome parameter. Safety, cumulative improvement rates of heartburn, the proportion of patients with complete heartburn resolution in the fourth week of treatment were the other outcome parameters.

Compared to the placebo group, the proportion of days without heartburn was not substantially higher in the vonoprazan group in the full analysis set but was significantly higher in the per-protocol-set sensitivity analysis as depicted in the following table:

In the vonoprazan group, early onset of response and considerably higher cumulative improvement rates of heartburn were witnessed. 

Compared with the placebo group, the distribution pattern illustrated a shift in the vonoprazan group to a higher proportion of days without heartburn during the treatment period, as depicted in the following figure:

In the post hoc analysis, an elevated proportion of patients with complete heartburn resolution in the fourth week of treatment were witnessed in the vonoprazan group. The incidence of treatment-emergent adverse events was found to be similar between treatment groups as depicted in the following table:

Most treatment-emergent adverse effects were mild in severity. Thus, vonoprazan is safe and effective to manage NERD patients with heartburn.