Gilead Announces New England Journal of Medicine Publication of Data that Demonstrate Bulevirtide with PegIFN Achieved Post-Treatment Undetectable HDV RNA

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced data from the Phase 2b MYR204 open-label study assessing the efficacy and safety of the first-in-class entry inhibitor bulevirtide as monotherapy and in combination with pegylated interferon alfa-2a (PegIFN), in adults living with compensated chronic hepatitis delta virus (HDV) infection. Published in the New England Journal of Medicine (NEJM), the data demonstrate that the investigational combination of bulevirtide 10 mg with PegIFN was superior to investigational bulevirtide 10 mg monotherapy in achieving undetectable HDV RNA (lower limit of quantification (LLOQ), target not detected) at Week 24 after the end of treatment (EOT). The end of study data presented at the European Association for the Study of the Liver (EASL) Congress 2024, demonstrate that treatment with bulevirtide 10 mg in combination with PegIFN maintained a 46% rate of undetectable HDV RNA at Week 48 after EOT, confirming its potential as a finite therapy for adults living with chronic HDV. HDV affects an estimated 5% of people living with chronic hepatitis B (HBV), with a global prevalence of more than 12 million people.

“HDV is the most severe form of viral hepatitis. For people living with HDV, bulevirtide 2 mg has been proven to be a successful long-term treatment approach, as highlighted in clinical trials and real-world data. These new data support the potential for bulevirtide as a finite treatment option, demonstrating that almost half of people treated with bulevirtide 10 mg in combination with PegIFN remained undetectable for HDV RNA one year after treatment cessation,” said Tarik Asselah, MD, PhD, Professor of Hepatology, Hôpital Beaujon APHP, Université Paris-Cité, Head of Viral Hepatitis, UMR1149 Inserm and principal investigator of the study. “These long-term data are the highest post-treatment response rates ever reported for HDV.”

Bulevirtide 2 mg remains the only approved treatment for adults with chronic HDV and compensated liver disease in the European Economic Area (EEA), Great Britain and Switzerland and is not approved in the U.S. Bulevirtide 10 mg is an investigational product and is not approved anywhere.

Data published in NEJM demonstrate that at Week 24 after EOT, undetectable HDV RNA was achieved by 32% and 46% of patients taking bulevirtide 2 mg in combination with PegIFN and bulevirtide 10 mg in combination with PegIFN, respectively. In the monotherapy groups, PegIFN monotherapy and bulevirtide 10 mg monotherapy, undetectable HDV RNA was achieved by 17% and 12%, respectively. The safety profiles of bulevirtide in combination with PegIFN were consistent with those of the individual components. The most frequent adverse events were leukopenia, neutropenia and thrombocytopenia, and most were mild to moderate.

Data presented at EASL (GS-002) demonstrate that at Week 48 after EOT, undetectable HDV RNA was achieved by 26% and 46% of patients taking bulevirtide 2 mg in combination with PegIFN and bulevirtide 10 mg in combination with PegIFN, respectively. In the monotherapy groups, PegIFN monotherapy and bulevirtide 10 mg monotherapy, undetectable HDV RNA was achieved by 25% and 12%, respectively.

“Chronic HDV can greatly impact those affected due to its rapid progression to liver failure, liver cancer and liver-related death. With these promising finite data for bulevirtide, we have the opportunity to support healthier futures for people living with HDV,” said Anu Osinusi, VP, Clinical Research for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences. “In addition to highlighting the curative potential of combination therapy for some people with chronic HDV, these final data support the safety profile of bulevirtide. Ultimately, our focus remains on bringing treatment options to more people living with chronic HDV.”

Also at EASL, late-breaking data (LB-309) on the pivotal Phase 3 MYR301 study evaluating bulevirtide as monotherapy for the treatment of adults with chronic HDV infection were also presented and reinforced bulevirtide as an efficacious and generally well-tolerated long-term treatment option. Patients had similar rates of combined response (virologic response and ALT normalization) at Week 144 compared to Week 96, with 57% and 54%, respectively, among those receiving bulevirtide 2 mg or 10 mg. This is consistent with and builds on the data shared at EASL 2023. Bulevirtide continued to be generally well-tolerated through Week 144, and the safety profile was similar between the bulevirtide 2 mg and 10 mg treatment arms, with the study investigators attributing no serious adverse events to bulevirtide treatment. Through 144 weeks of treatment, dose-dependent increases in bile acids remained asymptomatic, were not associated with any clinical sequelae and did not result in any discontinuations or treatment interruption.

In July 2023, the European Commission (EC) granted full Marketing Authorization (MA) for Hepcludex^® (bulevirtide) 2 mg for the treatment of adults with chronic HDV and compensated liver disease. Bulevirtide was initially granted conditional MA from the EC in July 2020 to provide people living with HDV urgent access to treatment. Bulevirtide’s conditional MA license in Great Britain was converted to a full MA in August 2023, and a full MA was granted in Switzerland in February 2024. In regions where it is not approved, including the U.S., bulevirtide 2 mg is an investigational product. In these regions, health authorities have not established the safety and efficacy of bulevirtide.

About MYR204

The MYR204 study was a randomized, open-label, controlled, parallel-group, multicenter, Phase 2b trial, in which a total of 174 patients were randomized and received PegIFN alone for 48 weeks; bulevirtide 2 mg with PegIFN for 48 weeks, followed by bulevirtide 2 mg alone for 48 weeks; bulevirtide 10 mg with PegIFN for 48 weeks, followed by bulevirtide 10 mg alone for 48 weeks; or bulevirtide 10 mg alone for 96 weeks. All patients were followed for an additional 48 weeks after EOT. The primary endpoint of MYR204 was undetectable HDV RNA at 24 weeks after EOT. Secondary efficacy endpoints included undetectable HDV RNA at Week 48 (all groups) during treatment, undetectable HDV RNA at Week 96 (all bulevirtide groups) during treatment, and undetectable HDV RNA at Week 48 after EOT (all groups).

About MYR301

MYR301 is an ongoing, Phase 3 clinical trial evaluating the long-term efficacy and safety of bulevirtide in 150 people living with chronic HDV randomly allocated to treatment with bulevirtide 2 mg once daily (n=49), 10 mg once daily (n=50) or no antiviral treatment (delayed treatment, n=51). Primary efficacy and safety data were assessed at Week 48. After Week 48, patients in the delayed treatment group of the study were switched to bulevirtide 10 mg once daily for an additional 96 weeks. The total duration of treatment across all groups in the study is 144 weeks. The primary endpoint, combined response, is defined as an undetectable HDV RNA or ≥ 2log₁₀ IU/ml decline from baseline and ALT normalization at Week 48. Secondary endpoints at Week 48 include undetectable HDV RNA (key secondary endpoint), ALT normalization, and a change from baseline in liver stiffness measured by transient elastography.

About HDV

HDV is considered the most aggressive or severe form of viral hepatitis, associated with more rapid progression towards liver-related death and liver cancer in people with HBV. On average, HDV progresses to cirrhosis within five years and to liver cancer within 10 years. Nearly 5% of people who have a chronic infection with HBV are estimated to have HDV, equating to 12-15 million people worldwide. The prevalence of HDV infection is largely underestimated due to lack of universal testing of HBV positive individuals for HDV.

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 primary biliary cirrhosis (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.

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 (bulevirtide); uncertainties relating to regulatory applications and related filing and approval timelines, including the risk that 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, 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.

Hepcludex, Gilead and the Gilead logo are registered trademarks of Gilead Sciences, Inc., or its related companies.

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