What the FDA Approval of Buleviratide (Hepcludex) Means for Chronic Hepatitis D Treatment

Last month, the FDA approved bulevirtide (Hepcludex) for the treatment of chronic hepatitis delta virus (HDV) infection, marking a significant milestone for patients living with the most severe forms of viral hepatitis.

Chronic hepatitis delta is associated with accelerated progression to liver cirrhosis, liver failure, and liver-related mortality compared with hepatitis B infection alone. Until now, treatment options have been limited, often relying on off-label therapies with inconsistent efficacy and tolerability.

"Having an approved therapy truly changes the conversation for patients," said Anu Osinusi, MD, vice president of Clinical Research for Hepatitis, Respiratory, and Emerging Viruses at Gilead. "It gives physicians a treatment specifically developed for this disease, and for people living with hepatitis delta, this really is an important step forward."

The approval was supported by data from the phase 3 MYR301 study, which evaluated the efficacy and safety of bulevirtide over a treatment period of up to 144 weeks. The study's primary endpoint combined virologic and biochemical response measures, including reductions in HDV RNA and normalization of alanine aminotransferase (ALT) levels.

According to the study results, 48% of patients receiving bulevirtide achieved the combined endpoint at week 48, compared with just 2% of patients in the delayed-treatment group. Investigators also observed sustained antiviral activity through 144 weeks, with response rates continuing to improve over time.

"Nearly half of the treated patients achieved the combined endpoint of virologic and biochemical response at week 48," Osinusi said. "These findings provide very important evidence that targeted therapy can meaningfully suppress viral activity and improve markers of liver inflammation."

Novel Mechanism Targets Viral Entry

Unlike previous approaches such as pegylated interferon, bulevirtide directly targets the sodium taurocholate cotransporting polypeptide (NTCP) receptor on hepatocytes. Both hepatitis B virus (HBV) and HDV rely on this receptor to enter liver cells.

By blocking NTCP, bulevirtide prevents viral entry into hepatocytes, targeting an earlier stage of the viral lifecycle than immune-stimulating therapies such as interferon.

Experts say this targeted mechanism reflects advances in the understanding of HDV pathogenesis and offers a treatment strategy specifically designed around the biology of hepatitis B and hepatitis delta coinfection.

The FDA approval includes a boxed warning regarding severe HBV and HDV exacerbations following treatment discontinuation. Clinicians are advised to closely monitor patients after stopping therapy, as increases in viral replication and liver inflammation may occur.

Gilead is working with healthcare providers, payers, and patient-support programs to facilitate access to the therapy. Eligible patients may receive assistance with coverage, reimbursement, and financial support through dedicated access programs.

With the approval of bulevirtide, clinicians now have a disease-specific therapy that may help slow progression of chronic hepatitis delta while providing patients with a long-awaited treatment option.