More than three years after Gilead Sciences’ hepatitis D drug brevirtide was rejected by the FDA over manufacturing and delivery concerns, the treatment has been given the go-ahead in the United States.
Just before Memorial Day weekend, the FDA approved Gilead’s Hepcrudex as the first treatment for chronic hepatitis D virus infection in the United States, granting early approval of the entry inhibitor for adults without cirrhosis or compensated cirrhosis, a complication of long-term hepatitis that causes progressive scarring of organs.
The FDA approved the therapy based on data from Gilead’s late-stage MYR301 trial, the company explained in a release, explaining that Hepculdex helped patients achieve statistically significant improvements in combined virologic and biochemical responses at 48 weeks compared to a control group that delayed treatment.
However, Gilead cautioned that in the body of evidence for Hepcrudex, improvements in disease-related clinical outcomes are “not established.” Given the drug’s accelerated approval in the United States, the company will likely need to confirm the drug’s benefits in confirmatory trials.
The primary endpoint for MYR301 focused on a combined response, defined as undetectable hepatitis D virus RNA and normalization of aminotransferases at 48 weeks. According to the FDA approval announcement, patients in the hepcrudex treatment group achieved an overall response rate of 48%, compared to just 2% in the delayed treatment group.
When Gilead first touted its Phase 3 victory for Hepculdex in the summer of 2022, the company emphasized its confidence in the therapy as a potential monotherapy for the treatment of chronic hepatitis D in the United States.
The drug, which won conditional approval in the European Union in 2020 and full approval in 2023, was the centerpiece of Gilead’s €1.15 billion acquisition of German biotech MYR in late 2020, with the California-based company aiming to quickly accelerate the launch of its hepatitis drug overseas as the US ruling loomed.
However, the drug received a surprise rejection in the U.S. in fall 2022, with the FDA rejecting Gilead’s application citing concerns about the drug’s manufacturing and delivery.
Gilead did not disclose the nature of the issue at the time.
Chronic hepatitis D infection is the most severe form of viral hepatitis and is associated with a “significantly higher risk” of rapid disease progression, liver failure and mortality than hepatitis B alone, according to Gilead. In the United States, it is estimated that approximately 2% to 4% of patients with chronic hepatitis B, or approximately 40,000 to 80,000 people, also have the delta pathogen.
Gilead did not publicly disclose the reasons for its initial U.S. rejection, but the company faced other regulatory headaches related to manufacturing and shipping in late 2021. At the time, 10 studies on the HIV drug lenacapavir (now approved as the ultra-long-acting PrEP drug Eztugo and the HIV drug Sunlenka) were put on hold over concerns that the drug solution was incompatible with the borosilicate vials in which it was stored, allowing “invisible” glass particles to contaminate the drug.
The following May, Gilead escaped FDA custody by proposing to use a separate vial made of aluminosilicate glass for lenacapavir, but faced rejection from the regulator.
