Crinetics reports topline results from paltusotine study

Crinetics announced topline results from its open-label Phase 2 carcinoid syndrome study of paltusotine, an oral, once-daily investigational compound being developed for the treatment of acromegaly and carcinoid syndrome. The Phase 2 trial was a randomized, open-label, parallel group, multi-center study evaluating the safety, tolerability, pharmacokinetics, and efficacy of paltusotine in people living with carcinoid syndrome. A total of 36 participants were randomized to receive either 40 mg or 80 mg of paltusotine for eight weeks, with the ability to dose titrate based on tolerability or inadequate control of symptoms during the first four weeks of treatment. Six participants in the 40 mg group increased their dose to 80 mg, and three participants in the 80 mg group increased to 120 mg. Thirty patients completed the randomized treatment phase, with one patient from the 40 mg group and five patients from the 80 mg group discontinuing treatment. Twenty-six of the 30 participants who completed the randomized treatment phase enrolled in the long-term extension phase of the study. Rapid and sustained reductions in flushing episodes and bowel movement; 63% reduction in mean flushing frequency for patients with greater than1/day at baseline; 60% reduction in mean excess BM frequency in patients with greater than3/day at baseline; 61% reduction in mean flushing severity and 64% reduction in mean BM urgency; reductions in frequency and severity of symptoms were observed within two weeks of paltusotine treatment and sustained through eight weeks in both naive/untreated patients and those switching from prior somatostatin receptor ligand therapy; overall pharmacokinetic profile of paltusotine in patients with carcinoid syndrome was consistent with expectations from healthy volunteers. Paltusotine was generally well-tolerated with a safety profile consistent with prior clinical studies. There were no treatment related severe or serious adverse events. The most frequently reported AEs included diarrhea, abdominal pain, nausea and headache AE findings were similar across 40 mg and 80 mg dosing groups. Levels of biomarkers serotonin and 5HIAA provide additional evidence of paltusotine activity in carcinoid syndrome.