- Design
- phase 3 randomised trial with 144 weeks of treatment and 96 weeks of post-treatment follow-up
- Population
- 150 patients with compensated chronic hepatitis D, randomised to bulevirtide 2 mg/day, 10 mg/day, or 48-week delayed start followed by 10 mg/day
- Primary outcome
- virologic response, combined response, ALT normalisation and undetectable HDV RNA
- Effect
- end of treatment virologic response 73%, 76%, 92%; at 96 weeks off treatment 33%, 30%, 32%; sustained undetectability in 23 of 64 (36%) undetectable at end of treatment; post-treatment hepatic serious adverse events in 20/142 (14%)
Bulevirtide is approved for compensated chronic hepatitis D in the US, EEA, UK, Switzerland, Russia, Australia and Canada, and the question nobody could answer was what happens beyond two years and after stopping. MYR301 randomised 150 patients to bulevirtide 2 mg or 10 mg daily for 144 weeks, or to a 48-week delay then 10 mg for 96 weeks, with 96 weeks of follow-up off treatment.
At the end of treatment, virologic response was 73%, 76% and 92% across the three arms, ALT normalisation 58–60%, combined response 54–57%, and undetectable HDV RNA 29%, 50% and 52%. Undetectability continued to improve with longer treatment, which is the argument for continuing rather than stopping at two years.
Then the relapse. At 96 weeks off treatment, virologic response had fallen to about 30% in every arm and combined response to 24%. Undetectable HDV RNA persisted in about 20%. Among the 64 patients undetectable at the end of treatment, 23 (36%) stayed undetectable — and the strongest predictor was how many continuous weeks they had been undetectable before stopping. Hepatic serious adverse events after stopping occurred in 20 of 142 patients (14%), resolving in 17.
The practical reading: bulevirtide is suppressive therapy, not a cure, and the default is to continue it. A patient with long-standing continuous undetectability may be a candidate to stop — with close monitoring, because one in seven had a post-treatment hepatic event.
- Treat as long-term suppression; do not plan a finite course unless there is a specific reason.
- If stopping is considered, the duration of continuous HDV RNA undetectability is the variable that predicts non-relapse — count the weeks.
- Monitor ALT and HDV RNA closely after stopping; 14% had a hepatic serious adverse event and they are the reason not to stop casually.
- HBsAg loss was not required for sustained response, which changes what an off-treatment goal looks like.
- Bulevirtide is not approved in India and hepatitis D is under-tested here — anti-HDV should be checked in every HBsAg-positive patient with disproportionate liver disease.
Why it matters
It answers whether this drug can be stopped, and the answer is mostly no — which determines cost, access and how the treatment is framed to a patient.
Don't overread it
The arms differ in treatment duration as well as dose, so the end-of-treatment response rates cannot be compared as a dose-response.
The statistics, in plain English
The 92% virologic response in the delayed-treatment arm looks better than the 73% and 76% in the immediate arms, but those patients had 96 weeks of 10 mg rather than 144 weeks of 2 or 10 mg, and the arms differ in baseline timing — this is not a dose comparison and should not be read as one. Virologic response here is defined as undetectable HDV RNA or a 2 log drop, so the higher figure includes patients with detectable virus; undetectability at 29% to 52% is the stricter and more meaningful number. With 49 to 51 patients per arm, differences of ten percentage points between arms are within noise.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for gastroenterology & hepatology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free