Gilead Announces NEJM Publication on Bulevirtide and PegIFN Achieving Post-Treatment Undetectable HDV RNA

Gilead Sciences, Inc. has recently unveiled data from its Phase 2b MYR204 open-label study, which investigates the efficacy and safety of bulevirtide, both as a standalone treatment and in combination with pegylated interferon alfa-2a (PegIFN), in adults with compensated chronic hepatitis delta virus (HDV) infection. The findings, published in the New England Journal of Medicine (NEJM), revealed that the combination of bulevirtide 10 mg with PegIFN outperformed bulevirtide 10 mg monotherapy in achieving undetectable HDV RNA levels at Week 24 post-treatment. Additionally, data presented at the European Association for the Study of the Liver (EASL) 2024 Congress confirmed that this combination maintained a 46% undetectable HDV RNA rate at Week 48 post-treatment, showcasing its potential as a finite therapy for chronic HDV patients.

HDV, impacting around 5% of individuals with chronic hepatitis B (HBV), affects over 12 million people globally. It is regarded as the most severe form of viral hepatitis, progressing rapidly to complications like liver cancer and liver failure. Current treatments are limited, with bulevirtide 2 mg being the only approved therapy for chronic HDV in the European Economic Area, Great Britain, and Switzerland, although it remains unapproved in the United States.

The MYR204 study results highlighted that at Week 24 post-treatment, 32% and 46% of patients on bulevirtide 2 mg and 10 mg combined with PegIFN, respectively, achieved undetectable HDV RNA. Comparatively, the figures for PegIFN monotherapy and bulevirtide 10 mg monotherapy were 17% and 12%. The safety profile for the combination therapy was consistent with its individual components, with common adverse events being mild to moderate cases of leukopenia, neutropenia, and thrombocytopenia.

The EASL findings at Week 48 post-treatment further supported the combination therapy, with 26% and 46% of patients on bulevirtide 2 mg and 10 mg with PegIFN achieving undetectable HDV RNA. For the monotherapy groups, the rates were 25% for PegIFN and 12% for bulevirtide 10 mg.

Professor Tarik Asselah, the principal investigator, emphasized the significance of these results, noting that nearly half of the patients treated with the combination remained undetectable for HDV RNA a year after ending treatment. This marks the highest post-treatment response rates ever documented for HDV, suggesting a finite treatment option for this severe disease.

Additionally, late-breaking data from the Phase 3 MYR301 study presented at EASL reinforced bulevirtide's efficacy and safety as a long-term monotherapy for chronic HDV. The study involved 150 patients, showing consistent combined response rates (virologic response and ALT normalization) at Weeks 144 and 96 for both bulevirtide 2 mg and 10 mg dosages, and the therapy was generally well-tolerated.

In July 2023, the European Commission granted full Marketing Authorization (MA) for Hepcludex® (bulevirtide) 2 mg for adult chronic HDV patients with compensated liver disease. This followed a conditional MA granted in July 2020 to ensure urgent access to treatment. The MA was also fully granted in Great Britain and Switzerland in 2023 and 2024, respectively. In regions where it remains unapproved, including the U.S., bulevirtide 2 mg is classified as investigational.

The MYR204 study was a randomized, open-label, controlled Phase 2b trial involving 174 patients receiving various combinations and dosages of PegIFN and bulevirtide over 48 to 96 weeks, followed by a 48-week post-treatment observation period. The primary endpoint was undetectable HDV RNA at Week 24 post-treatment, with secondary endpoints including undetectable HDV RNA at Weeks 48 and 96 during treatment.

The MYR301 Phase 3 trial continues to evaluate the long-term efficacy and safety of bulevirtide in chronic HDV patients, with primary and secondary endpoints assessed at Week 48. The trial aims to establish combined response rates, undetectable HDV RNA levels, ALT normalization, and liver stiffness changes.

Gilead Sciences remains committed to pioneering treatments for liver diseases, striving for breakthroughs that offer hope and a potential cure for viral hepatitis and other liver conditions. Through innovative research and collaborative efforts, Gilead continues to work towards a future free of liver disease.