FOSTER CITY, Calif.--(BUSINESS WIRE)--Gilead Sciences, Inc. (Nasdaq:GILD) today announced new data to be presented at the European Association for the Study of the Liver (EASL) Congress 2023, June 21-24, 2023. Key findings from more than 70 presentations will include Week 96 data from the pivotal Phase 3 study of Hepcludex® (bulevirtide) evaluating the efficacy and safety for the treatment of hepatitis delta virus (HDV) and late-breaking data on the impact of continued treatment with bulevirtide. Gilead will also present real-world data on efforts that support the World Health Organization’s (WHO) goal of eliminating viral hepatitis as a public health threat by 2030 and long-term results from ongoing studies of Vemlidy® (tenofovir alafenamide) in chronic hepatitis B (HBV). Results from ongoing research in liver fibrosis from across nonalcoholic steatohepatitis (NASH) and primary sclerosing cholangitis (PSC) will also be presented.
“We are pleased to share our latest viral hepatitis and liver fibrosis data at EASL 2023 as we strive to support the needs of patients and help achieve the WHO goal of viral hepatitis elimination by 2030,” said Frank Duff, MD, Senior Vice President, Virology Therapeutic Area Head, Gilead Sciences. “Despite the significant progress that has been made, considerable challenges still remain for those living with liver disease. We are proud to be able to share our ongoing research and efforts to help address these needs.”
Advancing Treatments in HDV and HBV
As a leader in hepatitis delta research, Gilead will present 15 abstracts in HDV, including the latest Week 96 data from the pivotal Phase 3 MYR301 study of bulevirtide in chronic HDV patients (OS-068). Data on the improved virologic and biochemical response with continued treatment with bulevirtide for 96 weeks in non- and partial-responders (LBP-20) will also be presented. These data reinforce the efficacy and safety of bulevirtide and demonstrate the benefits of continued treatment for people living with HDV, the most severe form of viral hepatitis.
Real-world data from a retrospective observational cohort study will be presented, highlighting a higher prevalence of comorbidities at baseline and an increased risk of liver-related outcomes for people with HDV/HBV co-infection compared to individuals with HBV mono-infection (WED-116). Data will also be presented on the impact of HDV on fatigue and health-related quality of life among untreated individuals living with HDV (FRI-124) highlighting the significant disease burden and high associated healthcare-related costs.
In HBV, final 8-year safety (SAT-153) and efficacy (OS-067) data will be presented from the two global Phase 3 studies (Study 108 and Study 110) evaluating long-term outcomes in chronic HBV patients treated with tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) who subsequently switched to TAF.
Helping to Achieve the WHO Goal of Hepatitis Elimination
Gilead will present nine hepatitis C (HCV) related abstracts that reinforce the need for tailored approaches for screening, linkage to care and management of HCV, and highlight the real-world impact of potential drug-drug interactions (DDIs) to optimize treatment decisions and decrease healthcare resource utilization (HCRU) and costs.
Data include results on optimizing screening and linkage to care which is critical on the path to hepatitis elimination. Results from an initiative using machine learning to improve HCV screening and linkage to care will be presented and have been selected as part of the ‘Scientific Highlights’ (OS-091). Findings from a UK pilot project (FRI-182) conducted in partnership with Practice Plus Group will be presented, with the aim to improve screening and linkage to care for blood borne viruses in Immigration Removal Centers.
Real-world data from the U.S. will be presented (THU-218) evaluating DDI comedication use in people initiating treatment with pangenotypic direct-acting antivirals (DAAs). Among patients with baseline DDI-related comedication use, those initiating treatment with Epclusa® (sofosbuvir/velpatasvir) were less likely to discontinue their DDI-related comedication prior to DAA initiation than patients initiating treatment with glecaprevir/pibrentasvir. Additional research is needed to assess real-world consequences of potential DDIs.
Ongoing Research in Liver Fibrosis
Gilead will present data on the effects of antidiabetic and lipid-lowering therapies on liver fibrosis biomarkers (OS-085) building further insights on the impact of these drugs in people with different genetic predisposition to NASH. Additionally, data will be presented on the association between non-invasive SomaSignal™ NASH scores and histologic assessments obtained from liver biopsy (SAT-438), advancing the potential to assess treatment responses in future NASH trials.
In PSC, Gilead will present data from the Phase 3 PRIMIS study (GS-US-428-4194) of investigational cilofexor (LBO-03). Additional presentations focus on the substantial impact on healthcare resource utilization of PSC (SAT-115) and the contribution of the NOTCH signaling pathway to the progression of fibrosis in liver tissue from PSC patients (FRI-360).
Key Abstracts at EASL 2023:
Abstract |
Abstract Title |
HDV |
|
OS-068 |
Efficacy and safety at 96 weeks of bulevirtide 2 mg or 10 mg monotherapy for chronic hepatitis D: results from an interim analysis of a Phase 3 randomized study |
LBP-20 |
Continued treatment of early nonresponder or partial virologic responders with monotherapy in patients with chronic hepatitis D through week 96 leads to improvement in virologic & biochemical responses |
WED-116 |
A retrospective observational cohort study of liver-related events among individuals with hepatitis B virus infection with and without hepatitis delta virus infection |
FRI-124 |
The impact of hepatitis D virus infection on health-related quality of life and fatigue in patients untreated for HDV: descriptive results from a cross-sectional study across Italy, Germany, Spain and the US |
HCV |
|
OS-091 |
Finding undiagnosed hepatitis C cases: using machine learning to identify clinical attributes and social determinants of health to improve the screening-to-diagnosis ratio and improve efficiency and linkage to care |
THU-218 |
Evaluating utilization and management of comedications with potential for drug-drug interactions among patients with chronic hepatitis C initiating treatment with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir |
FRI-182 |
Improving blood borne virus screening in immigration removal centres in the UK |
HBV |
|
OS-067 |
Long-term efficacy of tenofovir alafenamide in HBeAg-positive and -negative chronic hepatitis B patients treated for up to 8 years in 2 Phase 3 studies |
SAT-153 |
Long term safety profile of tenofovir alafenamide in chronic hepatitis B patients; final 8-year results of 2 Phase 3 studies |
Liver Fibrosis |
|
OS-085 |
Use of antidiabetic and lipid-lowering medications associated with lower scores of liver fibrosis biomarkers in Nonalcoholic Steatohepatitis (NASH) patients |
SAT-438 |
Utility of SomaSignal™ panels for drug response and monitoring disease progression in patients with advanced fibrosis due to non-alcoholic steatohepatitis |
SAT-115 |
Healthcare resource use and costs among patients with primary sclerosing cholangitis in Sweden - a retrospective population-based cohort study |
FRI-360 |
Elevated JAG1-NOTCH signaling is associated with fibrosis stages in patients with PSC |
LBO-03 |
A Phase 3, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of cilofexor in patients with non-cirrhotic primary sclerosing cholangitis (PRIMIS) |
For more information, including a complete list of abstract titles being presented at the meeting, please visit https://www.easlcongress.eu/wp-content/uploads/2023/04/Accepted-abstracts_EASL-Congress-2023.pdf.
In April 2023, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended granting full Marketing Authorization (MA) for bulevirtide for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide was initially granted conditional MA in July 2020 to provide people living with HDV urgent access to treatment. In the U.S. and outside of the European Economic Area, bulevirtide is an investigational agent. In these regions, health authorities have not established the safety and efficacy of bulevirtide.
Cilofexor and selgantolimod are investigational compounds and are not approved by the FDA or any other regulatory authority; their safety and efficacy have not been established.
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 with compensated liver disease.
About HDV
Chronic hepatitis delta virus (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 likely currently co-infected with HDV and HBV. HDV co-infection is associated with a faster progression to liver fibrosis, cirrhosis, hepatic decompensation and an increased risk of liver cancer and death. In the U.S. and Europe, there are approximately 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 many 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 Epclusa, Vemlidy, Hepcludex (bulevirtide), cilofexor and selgantolimod; uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that the European Commission may not grant full Marketing Authorization of Hepcludex, and the FDA and other regulatory authorities may not approve bulevirtide 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 March 31, 2023, 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.
Hepcludex, Epclusa, 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 www.gilead.com, follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
