BOULDER, CO, USA I November 28, 2016 I Nivalis Therapeutics, Inc. (NVLS), a clinical stage pharmaceutical company focused on treating people with cystic fibrosis (“CF”), today announced topline results from the Company’s Phase 2 trial evaluating the efficacy and safety of two doses of cavosonstat, 200 mg and 400 mg, in adult patients with CF who had two copies of the F508del-CFTR mutation and were being treated with Orkambi™. There were no dose limiting toxicities and cavosonstat was well tolerated at all doses in the trial. The trial failed, however, to demonstrate benefit in absolute change in percent predicted FEV1, the trial’s primary endpoint, or in sweat chloride reduction at 12 weeks.
“While we are disappointed in the outcome of this trial, we plan to continue to investigate the therapeutic potential of cavosonstat and our S-nitrosoglutathione reductase (GSNOR) inhibitor portfolio to determine next steps,” said Jon Congleton, president and chief executive officer of Nivalis.
Summary of Key Data
The data announced today are from a Phase 2, double-blind, randomized, placebo-controlled, parallel-group trial that evaluated the efficacy and safety of two doses of cavosonstat administered twice daily (BID) in adult patients with CF who were homozygous for the F508del-CFTR mutation and being treated with Orkambi. The trial included a total of 138 adults who received treatment with cavosonstat (200 mg) with Orkambi (n=44), cavosonstat (400 mg) with Orkambi (n=48) and placebo with Orkambi (n=46) for 16 weeks. The trial included a 4-week withdrawal and follow-up period once patients had completed 12-weeks of dosing.
The primary endpoint of the trial was change in absolute percent predicted FEV1 from baseline to week 12. This and key secondary endpoints are shown in the table below.
| Primary and Key Secondary Endpoints at Week 12 | |||||||||||
| Placebo (N=46) |
200 mg BID (N=44) |
400 mg BID (N=48) |
Pooled Active (N=92) |
||||||||
| Absolute Change in FEV1 (% predicted) (Within group p-value) |
0.97 (0.36) |
0.39 (0.72) |
0.35 (0.73) |
0.37 (0.62) |
|||||||
| Relative Change in FEV1 (% predicted) (Within group p-value) |
1.87 (0.31) |
0.66 (0.72) |
1.11 (0.53) |
0.91 (0.48) |
|||||||
| Absolute Change in Sweat Chloride (mmol/L) (Within group p-value) |
-2.3 (0.16) |
-1.2 (0.46) |
-0.6 (0.69) |
-0.8 (0.44) |
|||||||
| Absolute Change in CFQ-R respiratory domain (Within group p-value) |
-3.03 (0.24) |
-3.15 (0.23) |
3.16 (0.21) |
0.16 (0.93) |
|||||||
| Absolute change in BMI (kg/m2) (Within group p-value) |
-0.09 (0.39) |
0.17 (0.09) |
0.17 (0.08) |
0.17 (0.02) |
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“We would like to express our sincere gratitude to everyone who participated in this trial, including the patients, their families, the trial investigators and our employees,” said Dave Rodman, chief medical officer and executive vice president of discovery at Nivalis. “Although we did not meet the primary endpoint, these data help inform the overall body of CF research, and we remain dedicated to completing our current clinical CF research program.”
Conference Call Details
Nivalis will host a conference call today at 5:00 pm Eastern Time to discuss the results and provide an update on the cavosonstat development program. The call can be accessed by dialing 877-407-2987 for callers in the United States and Canada and 201-378-4918 for international callers. The conference call will also be webcast live and can be accessed on the “Investors” section of the Nivalis website, www.nivalis.com. The webcast will be available on Nivalis’ website for 90 days.
About Nivalis Therapeutics, Inc.
Nivalis Therapeutics, Inc. (http://www.nivalis.com) is a clinical-stage pharmaceutical company committed to the discovery, development and commercialization of therapeutics for people with CF. In addition to developing innovative solutions intended to extend and improve the lives of people with CF, Nivalis plans to utilize its proprietary S-nitrosoglutathione reductase (GSNOR) inhibitor portfolio to develop therapeutics for other diseases.
About Cavosonstat
Cavosonstat works through a novel mechanism of action called GSNOR inhibition. Nivalis discovered and owns exclusive rights to cavosonstat in the United States (U.S.) and all other major markets, including U.S. composition of matter patent protection until at least 2031. Cavosonstat was granted Orphan Drug and Fast Track designations in CF by the FDA earlier this year. Nivalis has completed clinical studies with cavosonstat, including a Phase 1a dose-escalation safety study in healthy volunteers, a Phase 1b safety study and a phase 2 trial, added to Orkambi™ in people with CF who have two copies of the F508del-CFTR mutation.
About Cystic Fibrosis
CF is a life-shortening genetic disease that affects an estimated 70,000 people worldwide, predominantly in the United States and Europe, according to the Cystic Fibrosis Foundation (www.cff.org). CF is characterized by a defect in the chloride channel known as the “cystic fibrosis transmembrane conductance regulator,” or CFTR, and is caused by mutations in the CFTR gene.
SOURCE: Cystic Fibrosis
