Nivalis Therapeutics recently announced that it has fully enrolled and given a first dose of its investigational compound, N91115, to all cystic fibrosis patients taking part in a Phase 2 clinical trial testing the compound, whose generic name is cavosonstat, in combination with Orkambi (lumacaftor/ivacaftor).
“Completing enrollment in this Phase 2 study represents a critical milestone in our clinical development program for cavosonstat and moves us closer to our goal of bringing our novel stabilizer to people with CF,” Jon Congleton, president and chief executive officer of Nivalis, said in a press release, thanking participants and their families for their commitment.
Topline results from the 16-week trial are expected by the end of 2016.
About the clinical trial
“Study of N91115 in Patients With CF Homozygous for the F508del-CFTR Mutation (SNO-6)” (NCT02589236) is the larger of two Phase 2 trials investigating the safety and efficacy of two different doses of cavosonstat in people with CF.
A total of 138 adult CF patients have been enrolled at 46 sites in the U.S. All have two copies of the F508del mutation in the CFTR gene (causing CF).
The participants were divided into three groups, and each already received a first dose of either 200 mg or 400 mg cavosonstat, or a placebo. Treatment will continue for 12 weeks, with patients being given their assigned dose of either the drug or placebo twice a day on top of their usual Orkambi therapy, followed by four weeks of withdrawal. Neither the patients nor the clinicians know who is getting cavosonstat and who is getting placebo.
The effect of the drug candidate will be assessed by measuring lung function and comparing it to baseline.
CF is caused by a mutation in the CFTR gene. This leads to a defective CFTR protein, not able to acquire its proper three-dimensional shape and fulfill its role. The CFTR protein normally sits on the membrane of epithelial cells lining lung airways and works as an ion channel. It plays a role in transporting chloride ions from inside the cells to the mucus layer inside the airways. The mutated CFTR protein cannot reach the cell membrane, meaning that chloride ions cannot be transported. This affects the amount of water in the mucus and ultimately causes the mucus to become too thick, leading to the characteristic symptoms of CF.
Cavosonstat works by inhibiting an enzyme called S-nitrosoglutathione reductase (GSNOR), which is thought to modulate the unstable and defective CFTR protein. When GSNOR is blocked, GSNO levels are restored. This modifies the chaperones, which are responsible for CFTR degradation, and stabilizes the CFTR protein. In preclinical studies, cavosonstat was shown to increase and prolong the function of the CFTR protein, leading to an increase in net chloride secretion.
The safety of cavosonstat has already been tested in healthy volunteers and in CF patients in a Phase 1a and Phase 1b study, respectively. Cavosonstat was granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA) earlier this year.
The company also announced that the United States Adopted Names (USAN) Council approved “cavosonstat” as the unique non-proprietary or generic name for the N91115 compound.