A Glimmer of Hope for an Orphan Disease

This editorial explores the promising therapeutic potential of bulevirtide for chronic hepatitis D virus (HDV) infection, a rare and aggressive liver disease affecting an estimated 12 million people globally—most of whom also have hepatitis B virus (HBV). Chronic HDV qualifies for orphan drug designation due to its low U.S. prevalence and severe prognosis, with higher risks of cirrhosis, liver failure, and cancer. Bulevirtide blocks viral entry via the sodium taurocholate cotransporting polypeptide receptor, and received conditional approval in the EU in 2020 based on early efficacy. A recent phase 3 trial showed that 45–48% of treated patients achieved a virologic and biochemical response at 48 weeks, compared to 2% in the control group. However, only a small fraction reached undetectable HDV viremia (12–20%), and there was no decline in HBsAg levels. The durability of response and optimal dosing remain uncertain, and potential cure may require long-term therapy or combination treatments. A notable case of sustained virologic response post-treatment suggests cure may be possible, yet cautious interpretation is warranted. Ultimately, the trial provides cautious optimism for a historically neglected condition, though key clinical questions persist.

This editorial explores the promising therapeutic potential of bulevirtide for chronic hepatitis D virus (HDV) infection, a rare and aggressive liver disease affecting an estimated 12 million people globally—most of whom also have hepatitis B virus (HBV). Chronic HDV qualifies for orphan drug designation due to its low U.S. prevalence and severe prognosis, with higher risks of cirrhosis, liver failure, and cancer. Bulevirtide blocks viral entry via the sodium taurocholate cotransporting polypeptide receptor, and received conditional approval in the EU in 2020 based on early efficacy. A recent phase 3 trial showed that 45–48% of treated patients achieved a virologic and biochemical response at 48 weeks, compared to 2% in the control group. However, only a small fraction reached undetectable HDV viremia (12–20%), and there was no decline in HBsAg levels. The durability of response and optimal dosing remain uncertain, and potential cure may require long-term therapy or combination treatments. A notable case of sustained virologic response post-treatment suggests cure may be possible, yet cautious interpretation is warranted. Ultimately, the trial provides cautious optimism for a historically neglected condition, though key clinical questions persist.