Hepcludex demonstrates sustained efficacy and safety profile in people with chronic hepatitis delta virus at 96 weeks.- Gilead Sciences

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 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 III 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 III 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 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 greater than 2 log10 IU/mL from baseline; non-response and partial virologic response was defined as HDV RNA decline of less than 1-log10 IU/mL and greater than 1 but less than 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),

“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 : MYR 301 is an ongoing, Phase III 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 (< LLOQ (lower limit of quantification), target not detected) or greater than 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.

See- "A Phase III, Randomized Trial of Bulevirtide in Chronic Hepatitis D"; Heiner Wedemeyer, M.D., Soo Aleman, M.D., Ph.D., Maurizia Rossana Brunetto, M.D., Antje Blank, M.D., et al., for the MYR 301 Study Group. June 22, 2023 DOI: 10.1056/NEJMoa2213429.