– Recommendation Based on the RESPONSE Study
Which Demonstrated ALP Normalization in 25% of Participants at 12
Months and Statistically Significant Reduction of Pruritus Versus
Placebo –
– If Approved by the European Commission,
Seladelpar Would Provide an Important Treatment Option for People
Living with the Rare Liver Disease in the EU –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the
Committee for Medicinal Products for Human Use (CHMP) of the
European Medicines Agency (EMA) adopted a positive opinion
recommending 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. The final European
Commission decision is anticipated in the first quarter of 2025.
This follows the accelerated approval by the U.S. Food and Drug
Administration (FDA) in August 2024.
PBC is a rare, chronic, autoimmune disease of the bile ducts
that affects approximately 15 per 100,000 people in Europe,
primarily women, and can cause liver damage and possible liver
failure if untreated. The most common symptoms of PBC are pruritus
(chronic itch) and fatigue, which can be debilitating for some
people. The disease currently has no cure and treatment goals for
people living with PBC include suppressing liver damage and
reducing the symptoms related to cholestasis. The effect of
treatment on slowing disease progression 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.
“This positive opinion from the Committee confirms promising
clinical benefit and value of seladelpar, which has been
underscored by its differentiated body of data,” said Palak
Trivedi, MD, BSc (Hons), MBBS, MRCP (UK), ESEGH, PhD, Associate
Professor and Consultant Hepatologist at the Queen Elizabeth
Hospital in Birmingham. “After many years of treating people with
PBC, I have seen the critical unmet need for additional effective
and symptom-directed treatment options. Today’s recommendation of a
potential new therapy that can help treat both the disease and
improve symptoms that impact quality of life is a significant
milestone for the PBC community.”
The positive opinion was supported primarily by data 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 compared with 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. ALP is a cholestatic marker that is a predictor of risk
for liver transplant and death. Change from baseline pruritus score
at month 6 was a key secondary endpoint; treatment with seladelpar
led to a statistically significant reduction in pruritus compared
with placebo. Participants entering the study with moderate to
severe itch experienced a 3.2-point improvement on a pruritus scale
of 0-10 after six months of treatment with seladelpar, compared to
a decrease of 1.7 points with placebo.
“We are encouraged by the CHMP’s positive opinion as we are one
step closer to providing seladelpar to people living with PBC in
Europe,” said Timothy Watkins, MD, MSc, Vice President, Clinical
Development of Inflammation Therapeutics, Gilead Sciences. “There
are still people living with PBC who do not have an adequate
response to current medicines or who are still experiencing
symptoms, such as debilitating itch. As a leader in liver disease,
Gilead is committed to bringing forth therapies that not only
improve markers of disease progression but also help alleviate
symptoms which impact the lives of people living with this rare
liver condition.”
In addition to Europe, Gilead is working with regulatory
authorities on marketing applications for seladelpar in other parts
of the world. In August 2024, the FDA granted accelerated approval
for seladelpar for the treatment of PBC in combination with (UDCA)
in adults who have had an inadequate response to UDCA, or as
monotherapy in patients unable to tolerate UDCA. Continued approval
of seladelpar for the approved indication may be contingent on
verification and description of clinical benefit in confirmatory
trial(s).
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 primarily
affecting women (1 in 1,000 women over the age of 40 or about
110,000 people in Europe). 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,
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 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.
Livdelzi® (seladelpar) was granted accelerated approval for the
treatment of PBC by the U.S. Food and Drug Administration (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 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.
Seladelpar is also under review by the UK Medicines and Healthcare
products Regulatory Agency (MHRA).
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
(seladelpar) 10mg capsules
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 Livdelzi
(seladelpar) (such as the RESPONSE and any confirmatory studies);
uncertainties relating to regulatory applications and related
filing and approval timelines, including European Commission and
MHRA 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; 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.
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version on businesswire.com: https://www.businesswire.com/news/home/20241212516221/en/
Blair Baumwell, Media public_affairs@gilead.com
Jacquie Ross, Investors investor_relations@gilead.com
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