– More than 70 Clinical and Real-World Abstracts Address Key Treatment Needs in Liver Disease –
– Integrated Analyses from Three Studies Underscore the Efficacy and Safety Pro Hepcludex®, for the Treatment of Chronic Hepatitis Delta Virus –
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc., (Nasdaq: GILD) today announced that clinical and real-world data from more than 70 abstracts will be presented at the American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®, taking place from Nov. 4-8, 2022. Key presentations include Week 48 integrated efficacy and safety analyses from Phase 2 and Phase 3 studies of Hepcludex® (bulevirtide), Gilead’s first-in-class investigational treatment for chronic hepatitis delta virus (HDV), and preclinical data on hepatitis B virus (HBV), which was selected to be included in AASLD’s “Best of the Liver Meeting” meeting highlights. The oral presentation will share preclinical research on an investigational HBV therapeutic vaccine as a potential component for an HBV cure regimen. New data will also be presented on the efficacy and safety of Vemlidy® (tenofovir alafenamide) chronic treatment in HBV, and Epclusa® (sofosbuvir/velpatasvir) curative treatment in chronic hepatitis C (HCV) across specific populations.
“At this year’s The Liver Meeting, our latest research helps to address some of the most significant needs of people living with liver diseases globally. It includes analyses from our clinical program on bulevirtide for the treatment of chronic hepatitis delta virus and preclinical data demonstrating the progress Gilead is making on the journey towards a potential cure for hepatitis B,” said Anu Osinusi, Vice President, Clinical Research for Hepatitis, Respiratory and Emerging Viruses at Gilead. “Through our ongoing research programs, we continue our longstanding commitment to address the unmet needs of people impacted by liver diseases.”
Safety and Efficacy Pro Bulevirtide Further Demonstrated in Integrated Analyses
Gilead will present data from several clinical studies on bulevirtide, underscoring the clinical utility of bulevirtide as a potential treatment option for people living with chronic HDV. Data will be presented from two integrated analyses of Week 48 data from three studies evaluating the safety (MYR204) and efficacy (MYR203 and MYR301) of bulevirtide for the treatment of chronic HDV (PO-1016 and PO-1024).
Analyses of healthcare data will also be presented, highlighting the substantial economic cost, resource utilization and quality-of-life burden associated with HDV (PO-3469). An analysis of MYR301 using self-completed ratings of patients’ health evaluates the impact of bulevirtide across several quality-of-life markers (PO-1019).
Bulevirtide was granted Breakthrough Therapy and Orphan Drug designations by the FDA. Bulevirtide is not approved by the U.S. FDA and is conditionally authorized under the tradename Hepcludex® in the European Economic Area and the United Kingdom.
Early Research Exploring Potential HBV Cure Approach Selected for “Best of the Liver Meeting”
Gilead will present preclinical HBV research selected for the “Best of the Liver Meeting”. The preclinical data demonstrates that an alternating-vector immunization strategy, utilizing a combination of Pichinde virus (PICV) (GS-2829) and lymphocytic choriomeningitis virus (LCMV) vectors (GS-6779), could serve as a potential backbone component of an HBV cure combination regimen based on the magnitude and consistency of HBV-specific T cell responses (PO-23). This important research adds to the progress in Gilead’s cure research program for HBV.
Gilead will also present safety and efficacy data for Vemlidy® (tenofovir alafenamide 25 mg, TAF) in children and adolescents (age 6 to less than 18 years of age and weighing 25 kg or more) with chronic HBV. The data showed that the efficacy and safety observed at Week 24 was maintained through Week 48, while continued treatment with TAF for 48 weeks resulted in increased rates of virologic and biochemical responses (HBV DNA <20 IU/mL). No resistance was observed in this population at Week 48 (PO-1184).
Vemlidy is indicated for the treatment of chronic HBV in adults and pediatric patients 12 years of age and older with compensated liver disease. The use of Vemlidy for other patient populations is investigational, and the safety and efficacy for these uses have not been established. The U.S. full Prescribing Information for Vemlidy contains a BOXED WARNING for post-treatment severe acute exacerbation of hepatitis B. See below for U.S. Important Safety Information.
New Treatment Approaches for HCV Explored
To achieve the World Health Organization (WHO) goal of elimination of viral hepatitis as a public health threat by 2030, innovative care delivery models and rapidly effective treatment are needed to continue progress.
Gilead will present an interim analysis of a real-world study that found utilizing a test and treat strategy implemented by non-specialists with Epclusa® (400 mg sofosbuvir/100 mg velpatasvir tablets) treatment achieved similar sustained virologic response rates at 12 weeks as those patients treated by specialists; SVR12 was 100% in the non-specialist group and 97.6% among those managed by specialists (OS-1296). Another study of nearly 1,400 participants found undetectable HCV RNA was achieved in >90% of patients at only 4 weeks of treatment and in 99.9% at 12 weeks (PO-1245). Finally, an analysis of Gilead’s ReLink initiatives, which are designed to identify and engage people living with HCV into care, demonstrate that active case-finding, patient navigation and care coordination increased patient engagement and treatment success rates among people living with HCV (OS-25).
New Approaches to NASH Treatment and PSC Monitoring
Gilead continues to pursue scientific advances across the broader liver disease research and development program, including new approaches for potential treatment and monitoring in nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC).
Gilead will present data from the Phase 2b ATLAS Study utilizing SomaScan® plasma proteome analysis in people with NASH with advanced fibrosis, demonstrating specific activity of combination therapy with investigational compounds, cilofexor and firsocostat, compared to monotherapies (OS-75). Non-invasive tests to determine stage of fibrosis in PSC remain an unmet medical need for this patient population, where increased fibrosis is associated with a higher risk of liver-related morbidity. Gilead will present research indicating that blood-based and imaging-based non-invasive tests are useful in identifying significant fibrosis (Ludwig F2-F4) in patients with PSC (PO-4743).
The safety and efficacy of cilofexor and firsocostat have not been established. Cilofexor and firsocostat are investigational compounds and are not approved by the U.S. FDA or any other regulatory authority.
Select accepted abstracts being presented at AASLD 2022 include:
Abstract
Abstract Title
HBV
Oral 23
GS-2829 / GS-6779 HBV Therapeutic Vaccine Generates Robust, Polyfunctional, Genotype Cross-Reactive CD8 T Cell Responses Accompanied by High Titers of Anti-HBsAg Antibodies
Poster 1184
Safety and Efficacy at 1 Year in Children and Adolescents with Chronic Hepatitis B (CHB) Receiving Tenofovir Alafenamide (TAF)
HDV
Poster 1016
Bulevirtide Monotherapy is Safe and Well Tolerated in Patients with Chronic Hepatitis D (CHD): An Integrated Safety Analysis of 48-Week Data
Poster 1024
Efficacy of Bulevirtide as Monotherapy for Chronic Hepatitis D (CHD): Week-48 Results from an Integrated Analysis
Poster 3430
HDV Patient Perspective: The Impact of Disease and Current Unmet Needs
Poster 3469
Understanding the Economic and Quality of Life Burden of Chronic Hepatitis Delta: A Systematic Literature Review
Poster 1019
Bulevirtide Improves Health Related Quality Life Measured by EQ-5D VAS in Patients with Chronic Hepatitis Delta: An Exploratory Analysis of a Phase 3 Trial at 48 Weeks
HCV
Oral 1296
Patients with Chronic Hepatitis C Could Be Treated with Sofosbuvir/Velpatasvir for 12 Weeks by Non-Specialists: 2nd Interim Analysis of Prospective Study Helios-3
Oral 52
Effectiveness of Relink Initiatives to Re-engage Diagnosed-but-Untreated HCV-Positive Patients with Direct-Acting Antiviral Treatment
Poster 1245
Curing HCV with Direct-Acting Antiviral (DAA) Treatment: Adherence and Rapid Onset of HCV RNA Undetectability After 4 Weeks of Treatment with Sofosbuvir/Velpatasvir
NASH
Oral 75
Combination Therapy with Cilofexor and Firsocostat Improves Plasma Fibrosis Biomarkers in Patients with Advanced Fibrosis Due to Non-Alcoholic Steatohepatitis
Oral 76
Exploratory Analyses of NASH Histology Using CRN Scores Derived From a Multi-Stain Machine Learning Method
Poster 2324
Hsd17b13 Ablation Ameliorates NASH Fibrosis in Mice Through Regulation of Interferon Signaling and Hepatic Stellate Cell Activation
PSC
Poster 4743
Associations of AST to Platelet Ratio Index (APRI), Enhanced Liver Fibrosis (ELF) Score, Fibrosis-4 (FIB-4) and Liver Stiffness Measurement (LSM) with Fibrosis Stages in Patients with Primary Sclerosing Cholangitis (PSC)
For more information, including a complete list of abstract titles being presented at the meeting, please visit .
Please see below for the U.S. Indications and Important Safety Information, including BOXED WARNINGS, for Epclusa and Vemlidy.
U.S. Important Safety Information And Indication for Epclusa
BOXED WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN HCV/HBV COINFECTED PATIENTS
Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with EPCLUSA. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
Contraindications
If EPCLUSA is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
Warnings and Precautions
Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with EPCLUSA due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
Risk of Reduced Therapeutic Effect Due to Use with P-gp Inducers and/or Moderate to Strong Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John’s wort and carbamazepine are not recommended for use with EPCLUSA as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.
Adverse Reactions
The most common adverse reactions (≥10%, all grades) with EPCLUSA in adults and pediatric patients 6 years of age and older were headache and fatigue; and when used with RBV in adults with decompensated cirrhosis were fatigue, anemia, nausea, headache, insomnia and diarrhea. The most common adverse reactions (≥10%, grade 1 or 2) in pediatric patients less than 6 years of age were vomiting and spitting up the drug.
Drug Interactions
Coadministration of EPCLUSA is not recommended with topotecan due to increased concentrations of topotecan.
Coadministration of EPCLUSA is not recommended with proton-pump inhibitors, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.
Consult the full Prescribing Information for EPCLUSA for more information on potentially significant drug interactions, including clinical comments.
Indication
EPCLUSA is indicated for the treatment of adult and pediatric patients 3 years of age and older with chronic hepatitis C virus genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis and in combination with ribavirin for those with decompensated cirrhosis.
U.S. Important Safety Information and Indication for Vemlidy
BOXED WARNING: POST TREATMENT SEVERE ACUTE EXACERBATION OF HEPATITIS B
Discontinuation of anti-hepatitis B therapy, including VEMLIDY, may result in severe acute exacerbations of hepatitis B. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue anti-hepatitis B therapy, including VEMLIDY. If appropriate, resumption of anti-hepatitis B therapy may be warranted.
Warnings and Precautions
Risk of Development of HIV-1 Resistance in HBV/HIV-1 Coinfected Patients: Due to this risk, VEMLIDY alone should not be used for the treatment of HIV-1 infection. Safety and efficacy of VEMLIDY have not been established in HBV/HIV-1 coinfected patients. HIV antibody testing should be offered to all HBV-infected patients before initiating therapy with VEMLIDY, and, if positive, an appropriate antiretroviral combination regimen that is recommended for HBV/HIV-1 coinfected patients should be used.
New Onset or Worsening Renal Impairment: Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome have been reported with TAF-containing products. Patients with impaired renal function and/or taking nephrotoxic agents (including NSAIDs) are at increased risk of renal-related adverse reactions. Discontinue VEMLIDY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Monitor renal function in all patients – See Dosage and Administration.
Lactic Acidosis and Severe Hepatomegaly with Steatosis: Fatal cases have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate (TDF). Discontinue VEMLIDY if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity develop, including hepatomegaly and steatosis in the absence of marked transaminase elevations.
Adverse Reactions
Most common adverse reactions (incidence ≥5%; all grades) in all clinical studies through week 144 were headache, upper respiratory tract infection, abdominal pain, cough, back pain, arthralgia, fatigue, nausea, diarrhea, dyspepsia, and pyrexia.
Drug Interactions
Coadministration of VEMLIDY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of tenofovir and the risk of adverse reactions.
Coadministration of VEMLIDY is not recommended with the following: oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, or St. John’s wort. Such coadministration is expected to decrease the concentration of tenofovir alafenamide, reducing the therapeutic effect of VEMLIDY. Drugs that strongly affect P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) activity may lead to changes in VEMLIDY absorption.
Consult the full prescribing information for VEMLIDY for more information on potentially significant drug interactions, including clinical comments.
Dosage and Administration
Testing Prior to Initiation: HIV infection.
Prior to or When Initiating, and During Treatment: On a clinically appropriate schedule, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus.
Dosage: 1 tablet taken once daily with food.
Renal Impairment: Not recommended in patients with end stage renal disease (ESRD; eCrCl <15 mL/min) who are not receiving chronic hemodialysis; in patients on chronic hemodialysis, on hemodialysis days, administer VEMLIDY after completion of hemodialysis treatment. No data are available to make dose recommendations in pediatric patients with renal impairment.
Hepatic Impairment: Not recommended in patients with decompensated (Child-Pugh B or C) hepatic impairment.
Indication
VEMLIDY is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients 12 years of age and older weighing at least 25 kg with compensated liver disease.
About HDV
Chronic HDV is the most severe form of viral hepatitis and can have mortality rates as high as 50% within five years in cirrhotic patients. HDV occurs only as a co-infection in individuals who have hepatitis B virus (HBV). It is estimated that at least 12 million people worldwide are currently co-infected with HDV and HBV. HDV co-infection is associated with a faster progression to liver fibrosis, cirrhosis and hepatic decompensation and an increased risk of liver cancer and death. In the U.S. and Europe, there are more than 230,000 people living with HDV; however, it remains underdiagnosed globally.
About Gilead Sciences in Liver Disease
For more than 20 years, Gilead has sought to address some of the biggest challenges in liver disease. The company has transformed the trajectory of multiple liver diseases through a relentless pursuit of innovation and pioneering access programs to bring meaningful therapies to people around the world. More work is required, and Gilead is committed to advancing innovative therapeutics to address the most pressing unmet needs in liver disease and overcoming barriers to better care.
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 and cancer. 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 or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing or additional clinical trials or studies, including those involving Hepcludex, Epclusa, Vemlidy, cilofexor and firsocostat; the possibility that Gilead may make a strategic decision to discontinue development of cilofexor, firsocostat and other investigational compounds, and as a result, the compounds may never be successfully commercialized; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the FDA or EC may not approve Hepcludex for the treatment of HDV, and the risk that any such approvals, if granted, may be subject to significant limitations on use; 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, 2022, 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.
U.S. Prescribing Information for Epclusa and Vemlidy, including BOXED WARNINGS, are available at
Epclusa, Hepcludex, Vemlidy, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
