– Now Approved, Seladelpar Can Provide an
Important Treatment Option for People Living With the Rare Liver
Disease in the European Economic Area –
– First and Only Treatment That Achieved
Statistically Significant Improvements Across Biochemical Response,
Alkaline Phosphatase Normalization, and Pruritus Versus
Placebo –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
European Commission (EC) has granted conditional marketing
authorization for seladelpar for the treatment of primary biliary
cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA)
in adults who have an inadequate response to UDCA alone, or as
monotherapy in those unable to tolerate UDCA. Seladelpar (an orphan
designated product) is now approved and will provide an important
treatment option for people living with the rare liver disease in
the European Economic Area (EEA).
“Today’s decision reinforces the clinical benefit and value of
seladelpar and offers people living with PBC in Europe an important
new treatment option,” said María-Carlota Londoño, MD, PhD,
Hepatologist at Hospital Clinic Barcelona. “There are people in
Europe who do not have an adequate response to first-line therapy
and seladelpar helps address the unmet need for effective and
symptom-directed treatment.”
PBC is a rare, chronic, autoimmune disease of the bile ducts
that affects approximately 22 out of 100,000 people in Europe. PBC
is more common in women and causes liver damage that can progress
to liver failure, particularly if left untreated. The most common
symptoms of PBC are pruritus (chronic itch) and fatigue, which can
be debilitating for some people. There is currently no cure for PBC
and treatment goals include slowing disease progression and
reducing the symptoms related to cholestasis (impaired bile flow),
such as cholestatic itch. The effect is primarily measured by an
improvement in liver biochemical tests, including the normalization
of alkaline phosphatase (ALP) levels, an important marker of
disease progression in PBC.
“People living with PBC in Europe have been waiting for
treatment advancements for many years. Up until now, there has been
no approved treatment for PBC addressing both the surrogate
biomarkers for underlying disease and pruritus, a common and at
times debilitating symptom of PBC. That changes today with the
conditional approval of seladelpar, which has been shown to both
help treat the disease and reduce pruritus,” said Timothy Watkins,
MD, MSc, Vice President, Clinical Development of Inflammation
Therapeutics, Gilead Sciences. “We look forward to working with
health authorities across Europe to bring this promising new
treatment to all those who could benefit.”
The EC’s decision follows the positive opinion of the Committee
for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) in December 2024, and is primarily based on
results from the pivotal placebo-controlled Phase 3 RESPONSE study.
In the study, 62% of participants taking seladelpar achieved the
primary endpoint of composite biochemical response at Month 12,
versus 20% of participants taking placebo. Treatment with
seladelpar led to normalization of ALP values 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
seladelpar demonstrated a statistically significant reduction in
pruritus compared with placebo. After six months of treatment with
seladelpar, participants entering the study with moderate to severe
itch experienced a 3.2-point improvement on a pruritus numerical
rating scale of 0-10, a clinically meaningful improvement, compared
to a decrease of 1.7 points with placebo. There were no
treatment-related serious adverse events, as determined by study
investigators. The most common adverse events, occurring in ≥ 5% of
participants in the seladelpar arm and at an incidence of ≥ 1%
higher than in the placebo arm were headache, nausea, abdominal
pain, and abdominal distension.
Gilead is now working with health authorities across Europe to
ensure people living with PBC who are eligible for seladelpar have
access as soon as possible. Seladelpar has been granted conditional
marketing authorization in the EU. Continued authorization of
seladelpar for the approved indication will be contingent on
verification and description of clinical benefit in confirmatory
trial(s). Outside of the EEA, seladelpar was granted accelerated
approval by the U.S. Food and Drug Administration (FDA) in August
2024. Most recently, seladelpar received approval by the UK
Medicines and Healthcare products Regulatory Agency (MHRA) in
January 2025. Regulatory review is also underway in Canada and
Australia.
About RESPONSE
(NCT04620733)
RESPONSE is a Phase 3, double-blind, placebo-controlled clinical
trial designed to evaluate the efficacy and safety of seladelpar in
adults with PBC who have shown inadequate response or intolerance
to first-line treatment with UDCA. The trial enrolled 193
participants across multiple sites worldwide. RESPONSE assessed key
biomarkers of cholestasis, including ALP levels, as well as
secondary endpoints related to liver function and patient quality
of life.
Participants in the RESPONSE trial received a daily oral dose of
10 mg of seladelpar or placebo for 12 months, with a focus on
measuring changes in ALP and other relevant liver function tests.
The trial aimed to address the high unmet need for effective
second-line therapies for individuals with PBC, providing important
insights into the long-term management of this chronic liver
disease.
About PBC
PBC is a rare, chronic inflammatory liver disease that affects
approximately 163,000 people in Europe. It primarily affects women
(1 in 1,000 women over the age of 40 globally). PBC is
characterized by impaired bile flow and the accumulation of toxic
bile acids in the liver, leading to inflammation and progressive
destruction of the bile ducts within the liver and causing
increased levels of 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 (chronic itch) and fatigue, which can be debilitating
for some people. Progression of PBC is associated with an increased
risk of liver-related mortality.
About Seladelpar
Seladelpar is an oral PPAR-delta agonist, or delpar, for the
treatment of PBC. PPAR-delta has been shown to regulate critical
metabolic and liver disease pathways. Preclinical and clinical data
indicate seladelpar has anticholestatic, anti-inflammatory,
antipruritic, and antifibrotic effects.
Seladelpar has potential to help meet the current unmet need of
people living with PBC, as the first and only treatment that
achieved statistically significant improvements across biochemical
response, ALP normalization, and pruritus versus placebo. Pruritus
is a common symptom that can significantly impair quality of life
in people with PBC.
In the U.S., seladelpar, which is marketed as Livdelzi®, was
granted accelerated approval for the treatment of PBC by the U.S.
FDA in August 2024. Seladelpar received FDA Breakthrough Therapy
Designation, as well as Orphan Drug Designation for the treatment
of people living with PBC. Seladelpar was also approved by the UK
MHRA in January 2025. Seladelpar has Priority Medicine (PRIME)
designation in the EU, which is assigned to optimize the
development of novel medicines that target conditions with an unmet
medical need for which no treatment options exists or where they
can offer a major therapeutic advantage over existing
treatments.
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 U.S. 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 had 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 (e.g., 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 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. The
company has helped to transform hepatitis C from a chronic
condition into one that can be cured for millions of people. For
individuals living with hepatitis B or D, Gilead's focus on
advancing medicines drives hope that today’s research will turn
into tomorrow’s cures. Beyond viral hepatitis, Gilead is working to
deliver advanced treatments for people living with PBC. The
commitment of Gilead doesn’t stop there. Through ground-breaking
science and collaborative partnerships, the company strives to
create healthier futures for everyone living with liver disease.
Gilead remains devoted 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 seladelpar
(such as the AFFIRM and any confirmatory studies); uncertainties
relating to regulatory applications and related filing and approval
timelines, including additional pending and potential applications
for seladelpar; 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; uncertainties regarding Gilead’s ability to coordinate
access to seladelpar in a timely manner or at all; the risk that
physicians may not see the benefits of prescribing seladelpar 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 September 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, 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).
View source
version on businesswire.com: https://www.businesswire.com/news/home/20250213709259/en/
Blair Baumwell, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
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