Hepcludex® (Bulevirtide) Demonstrates Sustained Efficacy and Safety Profile in People With Chronic Hepatitis Delta Virus at 96 Weeks

FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced Week 96 results from the pivotal MYR301 Phase 3 clinical trial evaluating the first-in-class entry inhibitor Hepcludex^® (bulevirtide) for the treatment of adults with chronic hepatitis delta (HDV) infection. These new data presented at the European Association for the Study of the Liver (EASL) Congress 2023 reinforce the role of bulevirtide as an efficacious and well-tolerated treatment for the management of chronic HDV. Bulevirtide remains the only approved treatment for HDV in the EU and is not approved in the U.S.

The new findings (OS-068) presented today reinforce the efficacy and safety of bulevirtide and demonstrate that additional improvements in combined response are observed at Week 96 compared with Week 48, with no signs of treatment resistance. An additional analysis from the MYR301 Phase 3 trial presented in a late-breaker (LBP-20) showed that study participants who appeared to not respond or only partially respond to bulevirtide treatment at Week 24, went on to achieve a virologic response at 96 Weeks with continued bulevirtide monotherapy.

“This latest data adds to the growing body of evidence establishing bulevirtide as an effective and well tolerated treatment for HDV when used for a longer duration. Importantly, we saw a response at 96 weeks even in people who initially showed only a partial decline in HDV viral load,” said Heiner Wedemeyer, MD, Director, Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at Hannover Medical School. “These findings demonstrate to clinicians and patients that with prolonged bulevirtide treatment, clinical benefit may be possible.”

The MYR301 Phase 3 data assessing the efficacy and safety of bulevirtide at 96 weeks (OS-068), builds on the Week 48 data shared at EASL’s ILC 2022 and was published yesterday in the New England Journal of Medicine. Study participants receiving either 2 mg or 10 mg bulevirtide achieved similar combined responses (ALT normalization and virological response) at Week 96. The combined virological and biochemical response rates continued to increase through Week 96 compared to Week 48, with response rates of 55% and 56% with 2 mg and 10 mg bulevirtide respectively. The safety profile at Week 96 is consistent with what was observed at Week 48, with no resistance observed and no serious adverse events attributed to bulevirtide treatment. Increases in bile acids without a correlation to pruritus or other symptoms were noted with bulevirtide treatment. Injection site reactions occurred in a higher proportion of study participants receiving 10 mg of bulevirtide.

In a new analysis (LBP-20), study participants treated with bulevirtide monotherapy who experienced suboptimal virological response (non-response or partial-response) at Week 24 were continued on treatment through Week 96. Among study participants who had no response or a partial-response at Week 24, 43% and 82% respectively achieved virological response by Week 96. Virologic response was defined as undetectable HDV RNA or a decrease by ≥ 2 log₁₀ IU/mL from baseline; non-response and partial virologic response was defined as HDV RNA decline of <1-log₁₀ IU/mL and ≥1 but <2-log₁₀ IU/mL respectively. The data also showed that ALT improvements at Week 96 could be seen in participants treated with bulevirtide with the earlier defined suboptimal virologic response. These results highlight that even in patients who have a suboptimal virologic response initially (after 24 weeks of treatment), prolonged treatment with bulevirtide led to virological and/or biochemical response in the majority of study participants.

“HDV is the most severe form of viral hepatitis and until recently there were no approved treatment options and patients faced a poor prognosis. The 96 Week data not only reinforces the efficacy and safety of bulevirtide as the first and only approved treatment in the EU for people living with HDV, but also demonstrates that bulevirtide has the potential to benefit a broader range of patients including those with suboptimal initial responses,” said Anu Osinusi, VP, Clinical Research for Hepatitis, Respiratory and Emerging Viruses, Gilead Sciences.

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.

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 was assessed at Week 48. After Week 48, participants 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 (<LoD (Limit of Detection) < LLOQ (lower limit of quantification), target not detected) 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 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 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, it is estimated that there are more than 230,000 people living with HDV; however, it remains widely underdiagnosed around the world.

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 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.

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