– First and Only Treatment to Demonstrate
Statistically Significant Reductions Across Key Biomarkers, ALP
Normalization and Pruritus Versus Placebo –
– Livdelzi Expands Gilead’s Long-Standing
Commitment to People Living with Liver Disease –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
U.S. Food and Drug Administration (FDA) has granted accelerated
approval for Livdelzi® (seladelpar) for the treatment of primary
biliary cholangitis (PBC) in combination with ursodeoxycholic acid
(UDCA) in adults who have had an inadequate response to UDCA, or as
monotherapy in patients unable to tolerate UDCA. The use of
Livdelzi is not recommended for people who have or develop
decompensated cirrhosis.
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The accelerated approval was based primarily on data from the
pivotal placebo-controlled Phase 3 RESPONSE study. In the study,
62% of participants taking Livdelzi achieved the primary endpoint
of composite biochemical response at month 12, versus 20% of
participants taking placebo. Treatment with Livdelzi led to
normalization of alkaline phosphatase (ALP) values, a cholestatic
marker that is a predictor of risk for liver transplant and death,
in 25% of trial participants at month 12. This change was not seen
in any trial participants receiving placebo. Change from baseline
pruritus score at month 6 was a key secondary endpoint; patients
treated with Livdelzi demonstrated a statistically significant
reduction in pruritus compared with placebo.
The FDA approved Livdelzi under accelerated approval based on a
reduction of ALP. Improvement in survival or prevention of liver
decompensation events have not been demonstrated. Continued
approval of Livdelzi for the approved indication may be contingent
on verification and description of clinical benefit in confirmatory
trial(s).
“More people are being diagnosed with PBC, impacting people of
varied ages, gender, race and ethnicity. Those living with PBC
share common symptoms, including incessant itching or skin-crawling
sensations, as well as debilitating fatigue that is made worse by
the itching at night,” said Carol Roberts, President, The PBCers
Organization. “The availability of a new treatment option that can
help reduce this intense itching while also improving biomarkers of
active liver disease is a milestone for our community.”
PBC is a rare, chronic, autoimmune disease of the bile ducts
that affects approximately 130,000 Americans, primarily women, and
can cause liver damage and possible liver failure if untreated. The
disease currently has no cure.
Livdelzi, an oral, peroxisome proliferator activated receptor
(PPAR) delta agonist, or delpar, is positioned to challenge the
current PBC standard of care, which falls short for many people who
experience inadequate response to treatment, putting them at risk
for continued liver damage. Livdelzi has demonstrated a sustained
efficacy and safety profile across its robust development program
to date, including a capacity to normalize ALP levels for some of
the people studied with PBC. Given ALP levels are recognized as an
important surrogate marker of disease progression in PBC, providers
are shifting to view ALP normalization as a treatment goal.
“People living with PBC have been waiting for treatment
advancements for many years. Today’s approval of Livdelzi, with its
distinct profile, provides them with an important new option,” said
Daniel O’Day, Chairman and Chief Executive Officer, Gilead
Sciences. “We look forward to leveraging Gilead’s long-standing
expertise in liver disease to bring this promising new treatment to
all those who could benefit.”
The RESPONSE study, in addition to other studies including the
long-term open-label ASSURE study and prior earlier phase studies,
together represent the experience with Livdelzi in more than 500
participants with PBC. Ongoing studies include the confirmatory
Phase 3 AFFIRM study, a randomized, placebo-controlled confirmatory
study designed to evaluate the effect of Livdelzi on clinical
outcomes in people with compensated cirrhosis due to PBC.
In the RESPONSE study, Livdelzi, given alone or in combination
with UDCA as an oral, once-daily medicine, reduced key biomarkers
of PBC disease and helped reduce pruritus (chronic itch), which is
a common symptom that can significantly impair quality of life in
people with PBC. Livdelzi is the only medicine to demonstrate
statistically significant and durable improvements in both pruritus
and markers of cholestasis related to the risk of disease
progression in a Phase 3 trial. The primary endpoint of the study
was a composite biochemical response at month 12, where biochemical
response was defined as achieving ALP less than 1.67-times upper
limit of normal (ULN), an ALP decrease of greater than or equal to
15% from baseline, and total bilirubin less than or equal to ULN.
ALP normalization (i.e., ALP less than or equal to ULN) at month 12
and change from baseline in pruritus score at month 6 were key
secondary endpoints. The most common adverse events (reported in
≥5% of trial participants in the Livdelzi arm and higher compared
to placebo) were headache, abdominal pain, nausea, abdominal
distension (swelling) and dizziness. There were no
treatment-related serious adverse events (SAEs), as determined by
the study investigators.
Commitment to Advocacy, Access and
Global Reach
The Gilead Support Path® Program offers information and
resources to help patients who are prescribed Livdelzi understand
coverage and financial options.
Following the acquisition of CymaBay, Gilead will continue to
provide funding to PBC patient organizations.
Livdelzi received FDA Breakthrough Therapy Designation, as well
as Orphan Drug Designation for the treatment of people living with
PBC.
Seladelpar has also been accepted for review by the UK Medicines
and Healthcare products Regulatory Agency (MHRA) and the European
Medicines Agency (EMA).
Please see below for U.S. Indication and Important Safety
Information for Livdelzi.
About Livdelzi
Livdelzi (seladelpar) is an oral PPAR-delta agonist, or delpar,
for the treatment of primary biliary cholangitis (PBC). 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, lipid
metabolism and transport and fibrosis.
Livdelzi has potential to help meet the current unmet need of
people living with PBC, as the first and only treatment that
achieved statistically significant reduction across biochemical
response, alkaline phosphatase (ALP) normalization, and pruritus
versus placebo. Pruritus is a common symptom that can significantly
impair quality of life in people with PBC.
As part of the FDA accelerated approval, Gilead has committed to
a confirmatory long-term outcomes study called AFFIRM, which has
already been initiated in people with compensated cirrhosis.
Continued approval may be contingent upon verification of clinical
benefit in confirmatory trial(s).
U.S. Indication for
Livdelzi
Livdelzi is indicated for the treatment of primary biliary
cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA)
in adults who have an inadequate response to UDCA, or as
monotherapy in patients unable to tolerate UDCA.
This indication is approved under accelerated approval based on
a reduction of ALP. Improvement in survival or prevention of liver
decompensation events have not been demonstrated. Continued
approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trial(s).
Limitations of Use: Use of Livdelzi is not recommended in
patients who have or develop decompensated cirrhosis (e.g.,
ascites, variceal bleeding, hepatic encephalopathy).
U.S. Important Safety Information for
Livdelzi
Warnings and Precautions
- Fractures: Fractures occurred in 4% of LIVDELZI-treated
patients compared to no placebo-treated patients. Consider the risk
of fracture in the care of patients treated with LIVDELZI and
monitor bone health according to current standards of care.
- Liver Test Abnormalities: LIVDELZI has been associated with
dose-related increases in serum transaminase (AST and ALT) levels
> 3 x ULN in patients receiving 50 mg and 200 mg once daily (5x
and 20x higher than the recommended dosage of 10 mg once daily).
Perform baseline clinical and laboratory testing when starting
LIVDELZI and monitor thereafter according to routine patient
management. Interrupt treatment if the liver tests (ALT, AST, total
bilirubin, and/or ALP) worsen, or if the patient develops signs and
symptoms of clinical hepatitis (eg, jaundice, right upper quadrant
pain, eosinophilia). Consider permanent discontinuation if liver
tests worsen after restarting LIVDELZI.
- Biliary Obstruction: Avoid use of LIVDELZI in patients with
complete biliary obstruction. If biliary obstruction is suspected,
interrupt LIVDELZI and treat as clinically indicated.
Adverse Reactions
- The most common adverse reactions (≥5%) with LIVDELZI were
headache (8%), abdominal pain (7%), nausea (6%), abdominal
distension (6%), and dizziness (5%).
Drug Interactions
- OAT3 Inhibitors and Strong CYP2C9 Inhibitors: Avoid
coadministration with LIVDELZI due to increased LIVDELZI
exposure.
- Rifampin: Monitor biochemical response (e.g., ALP and
bilirubin) when patients initiate rifampin during LIVDELZI
treatment. Coadministration may result in delayed or suboptimal
biochemical response of LIVDELZI.
- Dual Moderate CYP2C9 and Moderate-to-Strong CYP3A4 Inhibitors
and BCRP Inhibitors (eg, cyclosporine): Monitor closely for adverse
effects. Concomitant administration with LIVDELZI may increase
LIVDELZI exposure.
- CYP2C9 Poor Metabolizers Using Moderate-to-Strong CYP3A4
Inhibitors: Monitor more frequently for adverse reactions as
concomitant use of a moderate-to-strong CYP3A4 inhibitor in
patients who are CYP2C9 poor metabolizers may increase LIVDELZI
exposure and risk of LIVDELZI adverse reactions.
- Bile Acid Sequestrants: Administer LIVDELZI at least 4 hours
before or 4 hours after taking a bile acid sequestrant, or at as
great an interval as possible.
Pregnancy and Lactation
- Pregnancy: There are insufficient data from human pregnancies
exposed to LIVDELZI to allow an assessment of a drug-associated
risk of major birth defects, miscarriage, or other adverse maternal
or fetal outcomes. Report pregnancies to Gilead Sciences, Inc., at
1-800-445-3235.
- Lactation: There are no data on the presence of LIVDELZI in
human milk, the effects on the breastfed infant, or the effects on
milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother's clinical
need for LIVDELZI and any potential adverse effects on the
breastfed infant from LIVDELZI.
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
alkaline phosphatase (ALP), alanine transaminase (ALT) and
gamma-glutamyl transferase (GGT), enzymes found primarily in the
liver, as well as total bilirubin. The most common 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 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 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 Gilead’s ability 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 trials, including those involving Livdelzi
(seladelpar) (such as the RESPONSE, ENHANCE, ASSURE and any
confirmatory studies); uncertainties relating to regulatory
applications and related filing and approval timelines, including
MHRA and EMA reviews of seladelpar for the treatment of PBC; the
risk that any regulatory approvals, if granted, may be subject to
significant limitations on use or subject to withdrawal or other
adverse actions by the applicable regulatory authority; the risk
that physicians may not see the benefits of prescribing Livdelzi
for treatment of PBC; 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 June 30, 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 Gilead assumes no obligation and disclaims
any intent to update any such forward-looking statements.
Livdelzi, Support Path, Gilead and the Gilead
logo are registered trademarks of Gilead Sciences, Inc., or its
related companies.
U.S. full Prescribing Information for Livdelzi
is available at www.gilead.com.
For more information about Gilead, please visit
the company’s website at www.gilead.com, follow Gilead on X/Twitter
(@Gilead Sciences) and LinkedIn (@Gilead-Sciences).
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version on businesswire.com: https://www.businesswire.com/news/home/20240814469557/en/
Meaghan Smith, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
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