Bulevirtide Combination Therapy Shows Efficacy Achieving Undetectable Compensated Chronic Hepatitis Delta Virus RNA

Image Credit: Adobe Stock Images/jarun011

Results from the Phase IIb MYR204 study demonstrated that Gilead’s combination of bulevirtide with pegylated interferon alfa-2a (PegIFN) produced a higher rate of achieving undetectable HDV RNA in adults with compensated chronic hepatitis delta virus (HDV) infection compared to bulevirtide 10 mg monotherapy. The study, published in The New England Journal of Medicine found that at 24 weeks post-treatment, 46% of patients remained HDV RNA undetectable.¹

“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 study principal investigator Tarik Asselah, MD, PhD, professor of hepatology, Hôpital Beaujon APHP, Université Paris-Cité, head of viral hepatitis, UMR1149 Inserm, in a press release. “These long-term data are the highest post-treatment response rates ever reported for HDV.”

The randomized, open-label, controlled, parallel-group, multicenter MYR204 trial enrolled a total of 174 patients with compensated chronic HDV infection. Over 48 weeks, patients received PegIFN alone; 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. After treatment, patients were followed for an additional 48 weeks. The primary endpoint of the study was undetectable HDV RNA at 24 weeks after end-of-treatment (EOT), with secondary endpoints including undetectable HDV RNA at week 48 during treatment, undetectable HDV RNA at Week 96 during treatment, and undetectable HDV RNA at week 48 after EOT.

The data show that at week 24 after EOT, undetectable HDV RNA was observed in 46% of patients taking the bulevirtide 10 mg PegIFN combination, with the same being found in 32% of patients taking bulevirtide 2 mg in combination with PegIFN. PegIFN monotherapy was achieved by 17%, while the bulevirtide 10 mg monotherapy group achieved a 12% undetectable HDV RNA.

The safety profiles were consistent with individual components, with common adverse events (AEs) being mild to moderate. The most common AEs included leukopenia, neutropenia, and thrombocytopenia.

Further, the data was presented at this year’s European Association for the Study of the Liver Congress. The drug has received marketing authorization in multiple regions, such as the European Economic Area, Great Britain, and Switzerland, but is still at the investigational stage in regions included the United States.

Gilead also presented data from the Phase III MYR301 study, which supported bulevirtide as a well-tolerated, long-term treatment option, featuring similar response rates at week 144 compared to week 96. In this study, 57% of patients receiving the bulevirtide 2 mg monotherapy achieved undetectable HDV RNA, with 54% for those receiving 10 mg.¹

“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 a press release. “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.”

Reference

1. Gilead Announces New England Journal of Medicine Publication of Data that Demonstrate Bulevirtide with PegIFN Achieved Post-Treatment Undetectable HDV RNA. Gilead. June 6, 2024. Accessed June 6, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/6/gilead-announces-new-england-journal-of-medicine-publication-of-data-that-demonstrate-bulevirtide-with-pegifn-achieved-post-treatment-undetectable-hdv