– 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 –
FOSTER CITY, CA, USA I August 14, 2024 I 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.
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).
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.
SOURCE: Gilead Sciences
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– 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 –
FOSTER CITY, CA, USA I August 14, 2024 I 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.
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).
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.
SOURCE: Gilead Sciences
Post Views: 4,121
