TOPLINE:
Nearly half of patients with chronic hepatitis D virus (HDV) infection treated with bulevirtide achieved the combined primary endpoint of reduced or undetectable HDV RNA levels and normalized alanine aminotransferase (ALT) levels after 48 weeks in the phase 3 trial.
METHODOLOGY:
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A total of 150 patients with chronic HDV (with or without cirrhosis) were randomized to 2-mg or 10-mg bulevirtide once-daily via subcutaneous injection for 144 weeks, or no treatment for 48 weeks followed by bulevirtide 10 mg daily for 96 weeks (control group).
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The primary endpoint was a combination of decreased HDV RNA (defined as undetectable or a 2-log or greater decrease) and normalized ALT (defined as 31 U/L or less in women and 41 U/L or less in men), assessed at 48 weeks.
TAKEAWAY:
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The primary endpoint was reached by 45% of patients in the 2-mg group and by 48% of patients in the 10-mg group, versus just 2% in the control group (P < .001 for comparison of each dose group with the control group).
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Of the patients in the 2-mg group and 10-mg group, 12% and 20%, respectively, achieved undetectable HDV RNA levels at week 48.
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ALT levels normalized in 51% of the 2-mg group and in 56% of the 10-mg group, versus 12% of the control group.
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No treatment-related serious adverse events occurred. Bulevirtide led to dose-dependent increases in bile acid levels. Efficacy and safety will be evaluated for up to 144 weeks.
IN PRACTICE:
The surrogate endpoint of decreased HDV RNA and ALT levels is a “reasonably likely predictor of improved clinical outcomes” in patients with chronic HDV, the researchers write.
“There is tantalizing evidence that long-term suppression of HDV viremia may lead to clinical improvement and cure” and the final results of the trial are “eagerly awaited,” an editorialist adds.
SOURCE:
Heiner Wedemeyer, MD, Hannover Medical School, Germany, led the study, with funding from Gilead Sciences. It was published online July 6 in the New England Journal of Medicine, with an accompanying editorial.
LIMITATIONS:
The trial was not blinded, and it did not include patients with severe cirrhosis. Not all HDV and hepatitis B virus genotypes were represented, and most patients in the trial were White. The analysis evaluated data at week 48, when patients in two of the groups were still receiving treatment.
DISCLOSURES:
Wedemeyer acknowledged research funding, acting as a consultant to, and giving paid lectures on behalf of Gilead Sciences.
In 2022, the US Food and Drug Administration declined to approve bulevirtide for HDV, citing concerns over production and delivery.
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