Bulevirtide Acetate

Just before the Memorial Day weekend, the FDA signed off on Gilead’s once-rejected Hepcludex as the first treatment for chronic hepatitis D virus infection in the United States. More than three years after Gilead Sciences’ hepatitis D drug bulevirtide was rebuffed by the FDA due to manufacturing and delivery concerns, the treatment has since redeemed itself by scoring a green light in the U.S.Just before the Memorial Day weekend, the FDA signed off on Gilead’s Hepcludex as the first treatment for chronic hepatitis D virus infection in the United States, granting the entry inhibitor an accelerated approval in adults without cirrhosis or with compensated cirrhosis—a complication of long-term liver inflammation that leads to progressive scarring of the organ.The FDA cleared the therapy based on data from Gilead’s late-stage MYR301 study, in which Hepcludex helped patients achieve statistically significant improvements in a combined virologic and biochemical response at 48 weeks versus a control group that received delayed treatment, the company explained in a release. But Gilead caveated that improvement in disease-related clinical outcomes “has not been established” in its body of evidence for Hepcludex. Given the accelerated nature of the med’s U.S. nod, the company will likely need to confirm the drug’s benefit in a confirmatory trial.MYR301’s primary endpoint looked at combined response, defined as undetectable hepatitis D virus RNA and aminotransferase normalization at the 48-week mark. Patients in the Hepcludex arm achieved a combined response rate of 48% versus a slim 2% in the delayed treatment arm, per the FDA’s approval announcement.  When Gilead first touted its Hepcludex phase 3 win back in the summer of 2022, the company stressed its confidence in the therapy as a potential monotherapy for chronic hepatitis D treatment in the U.S. The drug—which won a conditional nod in the European Union in 2020 before scoring full approval there in 2023—was a central pillar of Gilead’s 1.15 billion euro buyout of German biotech MYR in late 2020, with the California-based company aiming to swiftly accelerate the hepatitis treatment’s launch overseas as a U.S. verdict loomed.But the drug landed a surprise U.S. rejection in the fall of 2022, when the FDA denied Gilead’s application on the grounds that it had manufacturing and delivery concerns with the drug. Gilead did not disclose the nature of the issue at the time.Chronic hepatitis D infection represents the most severe form of viral hepatitis and is linked to a “markedly higher risk” of quick disease progression, liver failure and mortality versus hepatitis B alone, according to Gilead. It’s estimated that in the U.S., around 2% to 4% of people who have chronic hepatitis B—or about 40,000 to 80,000 people—are also affected by the delta pathogen.  While Gilead has not publicized the reasons behind its initial U.S. rejection, the company faced a separate regulatory headache tied to manufacturing and delivery around late 2021, when 10 of its studies on the HIV med lenacapavir—now approved as the ultra-long-acting PrEP drug Yeztugo and HIV treatment Sunlenca—were put on hold over concerns that the drug solution was incompatible with the borosilicate vials it was stored in, leading to the potential for “sub-visible” glass particles to shed into the medication. In May of the following year, Gilead escaped the FDA’s hold by proposing to use a different vial for lenacapavir made from aluminosilicate glass, though not before facing a rejection from the regulator.