Bulevirtide (BLV), a first-in-class entry inhibitor, is approved in Europe for the treatment of chronic hepatitis delta (CHD). BLV monotherapy was superior to delayed treatment at week (W) 48, the ...primary efficacy endpoint, in the MYR301 study (NCT03852719). Here, we assessed if continued BLV therapy until W96 would improve virologic and biochemical response rates, particularly among patients who did not achieve virologic response at W24.
In this ongoing, open-label, randomized phase III study, patients with CHD (N = 150) were randomized (1:1:1) to treatment with BLV 2 mg/day (n = 49) or 10 mg/day (n = 50), each for 144 weeks, or to delayed treatment for 48 weeks followed by BLV 10 mg/day for 96 weeks (n = 51). Combined response was defined as undetectable hepatitis delta virus (HDV) RNA or a decrease in HDV RNA by ≥2 log10 IU/ml from baseline and alanine aminotransferase (ALT) normalization. Other endpoints included virologic response, ALT normalization, and change in HDV RNA.
Of 150 patients, 143 (95%) completed 96 weeks of the study. Efficacy responses were maintained and/or improved between W48 and W96, with similar combined, virologic, and biochemical response rates between BLV 2 and 10 mg. Of the patients with a suboptimal early virologic response at W24, 43% of non-responders and 82% of partial responders achieved virologic response at W96. Biochemical improvement often occurred independently of virologic response. Adverse events were mostly mild, with no serious adverse events related to BLV.
Virologic and biochemical responses were maintained and/or increased with longer term BLV therapy, including in those with suboptimal early virologic response. BLV monotherapy for CHD was safe and well tolerated through W96.
In July 2023, bulevirtide was fully approved for the treatment of chronic hepatitis delta (CHD) in Europe based on clinical study results from up to 48 weeks of treatment. Understanding the efficacy and safety of bulevirtide over the longer term is important for healthcare providers. In this analysis, we demonstrate that bulevirtide monotherapy for 96 weeks in patients with CHD was associated with continued improvements in combined, virologic, and biochemical responses as well as liver stiffness from week 48 at both the 2 mg and 10 mg doses. Patients with suboptimal virologic responses to bulevirtide at week 24 also benefited from continued therapy, with the majority achieving virologic response or biochemical improvement by week 96.
NCT03852719
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•BLV for 96 weeks maintained and/or improved responses compared to 48 weeks of treatment.•Efficacy was similar between the 2 mg and 10 mg doses of BLV.•In patients with a suboptimal early virologic response, improvements were observed with continued BLV.•Even in the absence of a virologic response, biochemical improvement can occur.•BLV was well tolerated with no discontinuations for adverse events through 96 weeks.
Hepatitis C is a virus affecting millions worldwide and is a major health risk. With the potentially severe adverse event profile of the current backbone of therapy, interferon, there is an impetus ...to discover interferon free treatment regimens. With the development of new oral direct acting antivirals, interferon free regimens may be available in the next few years. This article discusses some of the preliminary data from interferon free studies.
To determine adherence to Department of Health and Social Care target of fast-track pathway discharge for end-of-life care within 48 hours.
Multicentre audit in England using retrospective analysis ...of patient records for fast-track pathway tools submitted between 1 March 2019 and 31 March 2019.
Most patients (72%) were not discharged within the 48-hour target. There was significant variability in success between hospital sites. Delays in discharge were most frequently considered to be secondary to delays in sourcing packages of care and 24-hour care facility placements. Involvement of specialist discharge nurses in paperwork submission improved rates by Commissioning Care Groups. Patients who died in hospital had significantly longer admissions than those who were discharged (discharged 19 days (IQR 11-28) vs died 28 days (IQR 18-42); p=0.039). This was entirely accounted for by increased numbers of days between admission and first suggestion of fast-track pathway discharge in those who died in hospital (discharged 9 days (IQR 5-19), died 15 days (IQR 9-33); p=0.003).
We demonstrated a delay in the fast-track pathway discharge process with significant variation in success of the discharge process at different geographical locations.
Hepatitis B is a DNA virus affecting hundreds of millions of individuals worldwide. As the clinical sequelae of cirrhosis and hepatocellular cancer are increasingly recognized to be related to viral ...levels, the impetus increases to offer treatment to those previously not treated. With the development of more robust antivirals with reasonable safety profiles, long-term treatment is becoming more common. The oral nucleos(t)ide analogs have become the preferred first-line therapies for most genotypes of hepatitis B. Five are now available, all with different potencies and resistance profiles. Long-term data spanning several years are now available for most compounds in this arena. This article focuses on the common natural variants and those secondary to nucleos(t)ide therapy, as well as diagnostic methods to detect resistance.
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