Date: 2015-12-01
Type of information: Treatment of the first patient
phase: 2
Announcement: treatment of the first patient
Company: Nivalis Therapeutics (USA - CO)
Product: N91115 (S-nitrosoglutathione reductase inhibitor) with lumacaftor/ivacaftor (Orkambi™)
Action
mechanism: CFTR potentiator/cystic fibrosis transmembrane regulator (CFTR) protein modulator. N91115 works through a novel mechanism of action called S-nitrosoglutathione reductase (GSNOR) inhibition that is presumed to modulate the unstable and defective CFTR protein responsible for CF. GSNOR inhibition restores GSNO levels, thereby modifying the chaperones responsible for CFTR protein degradation. In preclinical testing, this stabilizing effect was shown to increase and prolong the function of the CFTR protein and may lead to an increase in net chloride secretion. This effect is both complementary and agnostic to other CFTR modulators, like Orkambi™. Nivalis discovered and owns exclusive rights to N91115 in the United States and all other major markets, including U.S. composition of matter patent protection until at least 2031.
Disease: cystic fibrosis in patients who have two copies of the F508del mutation
Therapeutic area: Rare diseases - Genetic diseases
Country: USA
Trial
details: The 12-week, double-blind, randomized, placebo-controlled, parallel group study is designed to investigate the efficacy and safety of two doses of N91115, 200mg and 400mg, administered twice daily in 135 adult patients with CF who are homozygous for the F508del-CFTR mutation and being treated with Orkambi™. The primary clinical efficacy outcome will be the absolute change from baseline in percent predicted FEV1, and secondary outcomes will include changes in sweat chloride, the CFQ-R Respiratory Symptom scale and Body Mass Index (BMI). (NCT02589236)
Latest
news: * On December 1, 2015, Nivalis Therapeutics announced the first patient was dosed in the Phase 2 clinical study of its lead investigational drug, N91115, a stabilizer of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. N91115 is being studied for the treatment of CF patients who have two copies of the F508del mutation, when added to Orkambi™ (lumacaftor/ivacaftor). The study is expected to be completed in the second half of 2016. Nivalis Therapeutics has completed clinical studies with N91115, including a Phase 1a dose-escalation safety study in healthy volunteers, and a Phase 1b safety study in people with CF who have two copies of the F508del mutation. In preclinical studies, N91115 has been shown to increase the function of F508del-CFTR, the mutant protein that is estimated to be present in approximately 86 percent of people with CF in the United States and Europe.
