Nivalis Therapeutics Announces Results from Phase 2 Clinical Trial of Cavosonstat Added to Ivacaftor for Treatment of Cystic ...
February 23 2017 - 4:05PM
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.”
About Nivalis Therapeutics,
Inc.Nivalis Therapeutics, Inc. (http://www.nivalis.com) is
a pharmaceutical company that has historically been focused on the
discovery and development of product candidates for patients with
cystic fibrosis, or CF. Our GSNOR inhibitors selectively target an
enzyme known as S-nitrosoglutathione reductase, which we refer to
as GSNOR. GSNOR regulates levels of an endogenous protein known as
S-nitrosoglutathione, or GSNO. Depleted levels of GSNO have
been associated with CF, asthma, inflammatory bowel diseases and
certain cardiovascular diseases. However, in light of recent
disappointing results of a Phase 2 clinical trial of our lead
product candidate, cavosonstat, in CF, we determined to not pursue
the development of this compound in CF and to wind down our
research and development activities as we shift our strategic
emphasis to investigating and evaluating strategic
alternatives.
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 in 2016. Nivalis has completed clinical studies with
cavosonstat, including two Phase 1a dose-escalation safety studies
in healthy volunteers, a Phase 1b safety study and a Phase 2 trial
in adult patients with CF who had two copies of
the F508del-CFTR mutation and in the Phase 2 trial were
being treated with Orkambi and a second Phase 2 trial of
cavosonstat in patients with CF who had one copy of the
F508del-CFTR mutation and a second gating mutation, and were being
treated with Kalydeco.
Forward Looking StatementsThis
press release contains “forward-looking statements” within the
meaning of the Private Securities Litigation Reform Act of 1995,
including, but not limited to, statements related to the potential
for GSNOR inhibitors to improve nutritional status in CF. These
forward-looking statements are based on the current intent and
expectations of the management of the Company. These statements are
not guarantees of future performance or actions and involve risks
and uncertainties that are difficult to predict. The Company’s
actual performance in the timing and outcome of actions and events
may differ materially from those expressed or implied in the
forward-looking statements because such statements are based on
assumptions and projections relating to these activities that are
inherently uncertain and may also be affected by risks such as:
that certain clinical data from prior trials may not be predictive
of results achieved in other trials of a drug candidate relating to
the same or different indications; and the other risks and
uncertainties described in the Company’s SEC reports filed under
the Securities Exchange Act of 1934, including its most recent
annual report on Form 10-K filed with the Securities and Exchange
Commission on February 13, 2017. All information in this press
release is as of the date of this release, and Nivalis undertakes
no duty to update or revise this information unless required by
law.
Contacts:
Investor Relations
Mike Carruthers
1-720-945-7707
mike.carruthers@nivalis.com
Media Relations
Lindsay Rocco
1-862-596-1304
lrocco@elixirhealthpr.com
Alpine Immune Sciences (NASDAQ:ALPN)
Historical Stock Chart
From Mar 2024 to Apr 2024
Alpine Immune Sciences (NASDAQ:ALPN)
Historical Stock Chart
From Apr 2023 to Apr 2024