MYR301: What Happens When Bulevirtide Is Stopped in Chronic Hepatitis D: Journal of Hepatology | September 2026 | Phase III MYR301 Trial

Introduction:

Bulevirtide has transformed treatment of chronic hepatitis D (HDV), but the optimal treatment duration remains uncertain. Final MYR301 data address a crucial practical question: can treatment be safely stopped after prolonged viral suppression, and is the response maintained?

Why was this study needed?

Bulevirtide can achieve substantial HDV-RNA suppression during treatment.

The optimal duration of therapy remains undefined.

It is unclear how often virologic control persists after withdrawal.

Evidence is needed to identify patients who might eventually achieve a durable off-treatment response.

Key Findings:

150 patients received bulevirtide for up to 144 weeks, followed by 96 weeks off treatment.

At treatment completion, virologic response was 73–92% across treatment groups.

HDV RNA became undetectable in 29–52% of patients.

Two years after stopping therapy, virologic response had fallen to approximately 30–33%.

Combined biochemical and virologic response declined to approximately 24%.

Of 64 patients with undetectable HDV RNA at treatment completion, only 23 remained continuously undetectable throughout follow-up.

Sustained off-treatment control appeared more likely after a prolonged period of continuously undetectable HDV RNA before withdrawal.

Post-treatment hepatic serious adverse events occurred in 14%, highlighting the importance of close monitoring after stopping therapy.

Overall, most patients appear to require prolonged rather than routinely finite-duration bulevirtide therapy.

Bottom Line:

MYR301 shows that much of bulevirtide’s virologic benefit is lost after treatment withdrawal. Prolonged therapy should remain the default for most patients with chronic HDV, while treatment cessation requires careful selection and close follow-up.