Nivalis Therapeutics (NVLS) Says Cavosonstat Phase 2 Clinical Trial in CF Missed Primary Endpoint

February 23, 2017 4:28 PM EST
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Nivalis Therapeutics, Inc. (NASDAQ: NVLS), a pharmaceutical company historically focused on developing innovative solutions for people with cystic fibrosis (CF), today announced topline results from the Company's Phase 2 trial evaluating the efficacy and safety of cavosonstat at a dose of 400 mg in adult patients with CF who had one copy of the F508del-CFTR mutation and a second gating mutation, and were being treated with Kalydeco™ (ivacaftor). There were no dose limiting toxicities and cavosonstat was well tolerated in the trial. Cavosonstat, when added to Kalydeco therapy, did not demonstrate benefit in absolute change in percent predicted FEV1, the trial’s primary endpoint, or in sweat chloride reduction at 8 weeks.

Summary of Key DataThe data announced today are from a Phase 2, double-blind, randomized, placebo controlled, trial that evaluated the efficacy and safety of one dose of cavosonstat administered twice daily (BID) in adult patients with CF who were heterozygous for the F508del-CFTR mutation and a gating mutation, being treated with Kalydeco. The 12-week trial included a total of 19 adults who received treatment with cavosonstat (400 mg) added to Kalydeco (n=15) or with placebo added to Kalydeco (n=4). The trial included a 4-week withdrawal and follow-up period once patients had completed 8 weeks of dosing.

The primary endpoint of the trial was change in absolute percent predicted FEV1 from baseline to week 8. These primary and key secondary endpoints are shown in the table below.

Primary and Key Secondary Endpoint at Week 8

Cavosonstat 400 mg BID (N=15)
Absolute Change inFEV1 (% predicted) (Within group P-value) 0.26 (0.72)
Relative Change in FEV1 (% predicted) (Within group P-value) 0.58 (0.68)
Absolute Change in Sweat Chloride (mmol/L) (Within group P-value) -0.3 (0.85)
Absolute Change in CFQ-R respiratory domain (Within group P-value) -2.90 (0.35)
Absolute Change in BMI (Within group P-value) 0.21 (0.11)

The increase in body mass index (BMI) reflecting a gain in weight in this study was similar to increases in BMI observed in two prior studies of cavosonstat in CF patients homozygous for F508del-CFTR. In one study, cavosonstat was administered over 4 weeks to CF patients who were not being treated with OrkambiTM and in the other study cavosonstat was administered over 12 weeks to patients who were being treated with Orkambi. End of treatment BMI data from these studies are summarized in the table below. These data suggest that GSNOR inhibition may have improved the nutritional status of patients with CF in these studies.

Mean1 BMI Change from Baseline (± Standard Deviation) at End of Study after Treatment with
Cavosonstat in Patients with CF
SNO-4 (4-week treatment duration): CF Patients homozygous for F508del-CFTR not on Orkambi
Placebo (N=11)-0.05(± 0.32)
50 mg (N=12)-0.01(± 0.25)
100 mg (N=13)0.11(± 0.48)
200 mg (N=14)0.09(± 0.66)
All Active (N=39)0.07(± 0.49)
SNO-6 (12-week treatment duration): CF Patients homozygous for F508del-CFTR on Orkambi
Placebo (N=41)-0.09(± 0.50)
200 mg (N=44)0.16(± 0.71)
400 mg (N-46)0.17(± 0.73)
All active (N=90)0.172(± 0.72)
SNO-7 (12-week treatment duration): CF Patients heterozygous for F508del-CFTR and gating mutation on Kalydeco
400 mg (N=15)0.20(± 0.49)
1 Arithmetic mean
2 P < 0.05, all other P-values for change from baseline were >0.05

“We are sincerely grateful to those who participated in this trial, including the patients, their families, the trial investigators and our employees,” said Steven Shoemaker, M.D., Medical Director at Nivalis. “We hope that the data from this trial will help inform the overall body of CF research, and help others in the design of future CF trials.”



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