- Positive Results from Two-year Interim
Analysis Includes Participants from Phase 3 RESPONSE Study and are
Highly Consistent with One-year Interim Analysis -
- Reduction in Patient-Reported Pruritus
(Itching) was Rapid and Durable in Participants with Moderate to
Severe Symptoms -
- Subset Analysis of Participants with
Compensated Cirrhosis Demonstrated Clinically Meaningful
Improvements in Markers of Cholestasis and Liver Injury -
Gilead Sciences, Inc. (Nasdaq: GILD), following the recent
acquisition of CymaBay Therapeutics, Inc., today announced two-year
interim results from the ongoing ASSURE study of investigational
seladelpar for the treatment of primary biliary cholangitis (PBC),
a rare, chronic inflammatory liver disease. The two-year interim
analysis includes people living with PBC who participated in any
prior clinical studies of seladelpar (legacy studies) and
participants from the pivotal Phase 3 RESPONSE study. Results
demonstrated rapid and sustained improvements in markers of
cholestasis, including high rates of normalization of liver
biomarkers and a clinically meaningful reduction in pruritus
(itch). These most recent data were shared in a presentation during
the European Association for the Study of the Liver (EASL) Congress
2024 in Milan, Italy.
“The data presented at EASL further support the sustained
efficacy and safety profile of seladelpar observed across its
robust development program, including a capacity to normalize ALP
values for many of the people studied with PBC. Given ALP is
recognized as an important surrogate marker of disease progression
in PBC, providers are shifting to normalization as a treatment
goal, which could potentially be enabled by seladelpar, if
approved,” said Timothy Watkins, MD, MSc, Vice President, Clinical
Development of Inflammation Therapeutics, Gilead Sciences.
“Seladelpar is a potential best-in-class therapy that could
transform the treatment landscape for people living with PBC by not
only improving or even normalizing markers of liver function, but
also improving pruritis or itch. Pruritis is a particularly
burdensome symptom of PBC which can significantly disrupt a
person’s quality of life. We’re committed to transforming the
management of PBC and the lives of those impacted by this rare
disease as we work together to bring seladelpar to the community,
if approved.”
ASSURE is an open-label, long-term Phase 3 study evaluating the
safety and efficacy profile of seladelpar, a potent, selective,
orally active delpar, or selective peroxisome
proliferator-activated receptor delta (PPAR) agonist, in adults
with PBC. Participants received 10 mg seladelpar, once daily, for
up to 155 weeks in the current analysis of the ASSURE cohort. The
two-year interim analysis, with a data cutoff date of January 31,
2024, included 179 participants from legacy studies and 158
participants from the Phase 3 registrational RESPONSE study. Of the
99 participants from legacy studies completing 24 months of
treatment with seladelpar, 70% met the composite response endpoint,
which includes alkaline phosphatase (ALP) levels below 1.67 x the
upper limit of normal (ULN), a decrease in ALP levels of at least
15%, and total bilirubin (TB) levels at or below the ULN. In
addition, 42% of these participants achieved ALP normalization at
24 months, a marker of liver disease progression. For the 164
participants from legacy studies completing 12 months of treatment
with seladelpar, 73% achieved the clinically meaningful composite
response endpoint, with 42% experiencing ALP normalization.
“Currently, there is no cure for PBC. While there are lifelong
medicines that may slow liver damage and stop it from progressing,
current medications fall short in about 40% of people. This is
because many individuals continue to have abnormal liver tests on
the current treatment options, and these treatments don’t reduce
one of the main relentless symptoms, pruritis, which impacts the
quality of life in people living with PBC,” said Dr. Palak Trivedi,
BSc, MBBS, MRCP, PhD, Professor of Associate Professor and
Consultant Hepatologist, University of Birmingham, and presenter of
the study. “The long-term efficacy and safety interim results from
ASSURE demonstrate that seladelpar may meaningfully raise the bar
in PBC. Seladelpar can help people achieve significant reduction,
and in some cases, normalization of liver blood tests. At the same
time, seladelpar can also help lower itch intensity.”
For those participants who completed the 12-month RESPONSE study
after randomization to seladelpar, who continued into the ASSURE
study and received continuous seladelpar treatment for a total of
18 months (12 months in RESPONSE, six months in ASSURE, n=102), 62%
achieved the composite response endpoint, and 33% reached ALP
normalization. For participants who received seladelpar for 24
continuous months (n=29), 72% and 17% met the composite response
endpoint and ALP normalization, respectively. Additional study
findings demonstrate that of the 52 participants previously
randomized to placebo in the RESPONSE study, 75% met the composite
response endpoint, and 27% achieved ALP normalization following
cross-over to six months of treatment with seladelpar in ASSURE.
Following 12 months of treatment, 94% of those crossing over met
the composite response endpoint, and 50% reached ALP normalization
(n=16). Across all ASSURE participants, the safety profile was
favorable and generally well-tolerated with long-term use, with no
treatment-related serious adverse events as determined by the study
investigators. These results are similar to the results seen in an
earlier data cut presented at Digestive Disease Week last
month.
Patient-reported pruritus was also collected throughout the
ASSURE study using the numerical rating scale (NRS; 0-10). Among
the participants with baseline NRS≥4, sustained improvement in
pruritus was observed with a mean reduction of 3.8 and 3.1 points
at 12 and 24 months in participants from legacy studies,
respectively. For RESPONSE participants, a mean reduction of 3.8
was observed in both continuous and former placebo participants at
six months in the ASSURE study. These findings were consistent with
the results observed in the pivotal RESPONSE study, reinforcing the
durability of this treatment effect.
Interim results of a subset of participants with liver cirrhosis
from the open-label, long-term ASSURE safety study will be shared
as an oral presentation at EASL (Presentation ID: OS-019). These
participants with compensated cirrhosis, received a second year of
seladelpar treatment following their initial participation in the
Phase 3 RESPONSE study. Consistent with the results of the RESPONSE
trial, participants achieved clinically meaningful improvements in
markers of cholestasis and liver injury.
Among participants with compensated liver cirrhosis from legacy
studies who enrolled in the ASSURE study (n=35), 91% were female
with a mean age of 60.8 years. Additionally, 23% (8/35
participants) had portal hypertension, 89% were Child-Pugh (CP)
class A, and 11% were CP-B. At baseline, mean ALP was 245 U/L, TB
was 1.0 mg/dL (31% > ULN), and mean liver stiffness measure
assessed by FibroScan was 19.9 kPa. As of the data cutoff date
(January 31, 2024), 32 participants with compensated cirrhosis had
completed 12 months of treatment. Of those participants, 56%
(18/32) met the composite biochemical endpoint at Month 12, with
ALP normalization occurring in 47% (15/32 participants). No serious
adverse events were related to the study drug as determined by the
study investigators.
A New Drug Application (NDA) for seladelpar for the treatment of
primary biliary cholangitis, including pruritus, in adults without
cirrhosis or with compensated cirrhosis (Child-Pugh A) who are
inadequate responders or intolerant to ursodeoxycholic acid (UDCA),
has been accepted for priority review by the U.S. Food and Drug
Administration (FDA) with an anticipated decision in August 2024.
The U.K. Medicines and Healthcare Products Regulatory Agency (MHRA)
and the European Medicines Agency (EMA) have also accepted
seladelpar for review.
About ASSURE
(NCT03301506)
ASSURE is an open label study to evaluate the long-term safety
and tolerability of seladelpar in people with primary biliary
cholangitis (PBC) who have already participated in other PBC
clinical trials of seladelpar. The study is currently enrolling up
to 500 people living with PBC from across 160 sites around the
world. ASSURE will also assess the long-term efficacy of seladelpar
and its impact on important patient reported outcomes such as
cholestatic pruritis, or itch, which can have a significant impact
on the quality of life of people living with PBC.
Participants enrolled in ASSURE at the time of this interim data
analysis include participants from previous studies of seladelpar
in PBC, including the Phase 3 registrational RESPONSE study and the
other clinical trials, which include the Phase 2 dose-ranging
study, the Phase 3/4 long-term open label study and the Phase 3
ENHANCE program that were both terminated early, and the ongoing
open label study in people with PBC and hepatic impairment. The
majority of participants from the legacy studies have a gap of one
year or more off-treatment before enrollment in the study, and 19%
of participants had cirrhosis. Participants received an open-label
daily dose of 10 mg of seladelpar orally for up to 155 weeks in
ASSURE.
Interim results of ASSURE (Abstract #LB-283), titled “Long-term
efficacy and safety of open-label seladelpar treatment in patients
with primary biliary cholangitis (PBC): Interim results for 2 years
from the ASSURE study,” will be presented Dr. Palak Trivedi on
behalf of the ASSURE study investigators during the EASL 2024
Congress on June 5, 2024.
About Seladelpar
Seladelpar, an investigational treatment for people with PBC, is
a first-in-class oral, selective PPAR-delta agonist, or delpar.
PPAR-delta has been shown to regulate critical metabolic and liver
disease pathways. Preclinical and clinical data support its ability
to regulate genes involved in bile acid synthesis, inflammation,
fibrosis and lipid metabolism, storage, and transport. Seladelpar
is not approved by the FDA or any other regulatory authority
globally and has not been determined to be safe or efficacious for
any use.
About PBC
PBC is a rare, chronic inflammatory liver disease primarily
affecting women (1 in 1,000 women over the age of 40 or about
130,000 total people in the U.S.). PBC is characterized by impaired
bile flow (known as cholestasis) and the accumulation of toxic bile
acids in the liver, leading to inflammation and destruction of the
bile ducts within the liver and causing increased levels of ALP,
ALT, and GGT, enzymes found primarily in the liver, as well as
total bilirubin. The most common early symptoms of PBC are pruritus
and fatigue, which can be debilitating for some people. Progression
of PBC is associated with an increased risk of liver-related
mortality.
About CymaBay
CymaBay Therapeutics Inc. was acquired by Gilead Sciences in
March 2024. CymaBay Therapeutics, a Gilead Company, is a
clinical-stage biopharmaceutical company focused on improving the
lives of people with liver and other chronic diseases that have
high unmet medical need. Our deep understanding of the underlying
mechanisms of liver inflammation and fibrosis, and the unique
targets that play a role in their progression, helped CymaBay
receive breakthrough therapy designation and orphan drug status
from the U.S. Food and Drug Administration for seladelpar, a
first-in-class investigational treatment for people with PBC.
About Gilead Sciences in Liver
Disease
For decades, Gilead has pioneered the way forward to improve the
lives of people living with liver disease around the world. We have
helped to transform hepatitis C from a chronic condition into one
that can be cured for millions of people. For people living with
hepatitis B or D, our focus on advancing our medicines drives hope
that today’s research will turn into tomorrow’s cures. Beyond viral
hepatitis, we’re working to deliver advanced treatments for people
living with primary biliary cirrhosis (PBC). But our commitment
doesn’t stop there. Through our ground-breaking science and
collaborative partnerships, we strive to create healthier futures
for everyone living with liver disease. We are committed to a
future without liver disease.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis, COVID-19, cancer and inflammation. Gilead operates
in more than 35 countries worldwide, with headquarters in Foster
City, California.
Forward-Looking
Statements
This press release includes forward-looking statements, within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including the ability of Gilead and CymaBay to initiate, progress
or complete clinical trials within currently anticipated timelines
or at all, and the possibility of unfavorable results from ongoing
or additional clinical studies, including those involving
seladelpar (such as the ASSURE and RESPONSE trials); uncertainties
relating to regulatory applications and related filing and approval
timelines, including the risk that the FDA and other regulatory
authorities may not approve seladelpar for the treatment of PBC,
and the risk that any such approvals, if granted, may be subject to
significant limitations on use; the possibility that Gilead and
CymaBay may make a strategic decision to discontinue development of
programs for indications that are currently under evaluation and,
as a result, these programs may never be successfully
commercialized for such indications; and any assumptions underlying
any of the foregoing. These and other risks, uncertainties and
factors are described in detail in Gilead’s Quarterly Report on
Form 10-Q for the quarter ended March 31, 2024, as filed with the
U.S. Securities and Exchange Commission. These risks, uncertainties
and other factors could cause actual results to differ materially
from those referred to in the forward-looking statements. All
statements other than statements of historical fact are statements
that could be deemed forward-looking statements. The reader is
cautioned that any such forward-looking statements are not
guarantees of future performance and involve risks and
uncertainties, and is cautioned not to place undue reliance on
these forward-looking statements. All forward-looking statements
are based on information currently available to Gilead and CymaBay,
and Gilead and CymaBay assume no obligation and disclaim any intent
to update any such forward-looking statements.
CymaBay, the CymaBay logo, and GILEAD are
trademarks of Gilead Sciences, Inc. or its related companies.
For more information on Gilead’s commitment in
Liver Disease please visit www.gilead.com. For more information on
investigational seladelpar and ASSURE please visit
www.cymabay.com.
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version on businesswire.com: https://www.businesswire.com/news/home/20240604334684/en/
Meaghan Smith, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
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