R-Pharm Overseas, Inc.

Idiopathic recurrent pericarditis (IRP) is a rare autoinflammatory disease. Interleukin (IL)-1α and IL-1β are the pivotal cytokines in the pathophysiology of acute pericarditis and its recurrence. We created a phase II/III study with a new IL-1 inhibitor-goflikicept in IRP.

This study sought to evaluate the efficacy and safety of goflikicept treatment in patients with IRP.

We conducted a 2-center open-label study of goflikicept in patients with IRP with and without recurrence at time of enrollment. The study consisted of 4 periods: screening, run-in (open-label treatment period), randomized withdrawal, and follow-up. Patients with clinical response to goflikicept in the run-in period were randomized (1:1) to a placebo-controlled withdrawal period, where the time to first pericarditis recurrence (primary endpoint) was evaluated.

We enrolled 22 patients, and 20 of these patients were randomized. Reduction of C-reactive protein level accompanied by reduction of chest pain and pericardial effusion compared to baseline was demonstrated during the run-in period. Recurrence of pericarditis occurred in 9 of 10 patients in the placebo group, and there were no recurrence events in goflikicept group within 24 weeks after randomization (P < 0.001). A total of 122 adverse events were reported in 21 patients (95.5%), with no deaths and no new safety signals identified for goflikicept.

Treatment with goflikicept prevented recurrences and maintained IRP remission with a favorable risk-benefit ratio. Goflikicept reduced the risk of recurrence compared with placebo. (Study to Evaluate the Efficacy and Safety of RPH-104 Treatment in Patients With Idiopathic Recurrent Pericarditis; NCT04692766).

Treating patients who experience residual psychotic symptoms during remission of schizophrenia remains one of the most challenging problems. The mechanisms underlying these symptoms differ from those of acute hallucinations and delusions. 5-HT6 receptor antagonists have been considered promising agents in treatment of residual psychotic symptoms and cognitive dysfunction. The aim of the study was to assess the efficacy of a selective 5-HT6 inhibitor Avisetron in the reduction of residual psychotic symptoms in patients with schizophrenia on stable antipsychotic therapy.

Eighty clinically stable outpatient subjects with schizophrenia with residual psychotic symptoms were randomized in a double-blind manner to 6 weeks of Avisetron or placebo at 1:1 ratio. Subjects received 8 mg of Avisetron or placebo on top their stable antipsychotic treatment. Standard clinical scales and cognitive tests were used for endpoint assessment. The primary efficacy endpoint was the mean reduction of total Positive and Negative Syndrome Scale score after 6 weeks of treatment.

No significant differences in the primary and secondary endpoints were found between the groups. However, based on the subgroup analysis, the significant improvement of total Positive and Negative Syndrome Scale score and residual psychotic symptoms was observed in female patients.

It was a negative study with unexpected benefits of the drug only in females. We hypothesized that the role of patients' sex can impact the treatment response to serotonergic drugs in general. We suggest a possible synergistic interaction between estrogen and Avisetron by means of modulating the effect of estrogens on the serotonergic system. Future studies targeting the sex-related effects of serotonergic drugs are warranted.