More than three years after facing a regulatory setback, Gilead Sciences has received U.S. approval for Hepcludex, its treatment for chronic hepatitis D virus (HDV) infection. Shortly before the Memorial Day weekend, the U.S. Food and Drug Administration approved the therapy under an accelerated pathway for adults without cirrhosis or with compensated cirrhosis, a condition involving progressive liver scarring caused by long-term inflammation.
The approval makes Hepcludex the first treatment for chronic hepatitis D virus infection in the United States. The therapy, also known as bulevirtide, is an entry inhibitor and was cleared based on findings from Gilead’s phase 3 MYR301 study.
According to Gilead, patients treated with Hepcludex in the late-stage trial achieved statistically significant improvements in a combined virologic and biochemical response at 48 weeks compared with a control group that received delayed treatment.
The primary endpoint of MYR301 measured combined response, defined as undetectable hepatitis D virus RNA and normalization of aminotransferase levels at week 48. Based on the FDA’s approval announcement, 48% of patients treated with Hepcludex achieved a combined response, compared with 2% of those in the delayed-treatment group.
Gilead said that evidence showing improvement in disease-related clinical outcomes for Hepcludex remains incomplete. The company stated that “improvement in disease-related clinical outcomes has not been established” based on the evidence currently available. Because the drug was granted accelerated approval, Gilead will likely need to confirm the therapy’s benefit in a confirmatory study.
The U.S. authorization follows an earlier setback in 2022, when the FDA rejected Gilead’s application because of manufacturing and delivery concerns related to the treatment. At the time, the company did not disclose details about the issue.
Before receiving approval in the United States, Hepcludex had already secured regulatory clearances in Europe. The treatment received conditional approval in the European Union in 2020 and later obtained full approval in 2023. Hepcludex was also a central component of Gilead’s 1.15 billion euro acquisition of German biotechnology company MYR in late 2020, as the California-based company sought to accelerate the treatment’s launch overseas while awaiting a U.S. regulatory decision.
When Gilead reported positive phase 3 results for Hepcludex in the summer of 2022, the company said it was confident in the therapy’s potential as a monotherapy for chronic hepatitis D treatment in the United States.
Chronic hepatitis D infection is considered the most severe form of viral hepatitis and is associated with a “markedly higher risk” of rapid disease progression, liver failure and death compared with hepatitis B infection alone, according to Gilead. In the United States, an estimated 2% to 4% of people living with chronic hepatitis B, roughly 40,000 to 80,000 individuals, are also affected by hepatitis D.
Although Gilead did not explain the reasons behind Hepcludex’s initial rejection, the company encountered separate manufacturing and delivery-related regulatory issues involving its HIV drug lenacapavir. In late 2021, 10 studies involving the medicine were paused because of concerns that the drug solution was incompatible with borosilicate glass vials, raising the possibility of “sub-visible” glass particles entering the medication. In May of the following year, Gilead resolved the issue by proposing the use of aluminosilicate glass vials, allowing the FDA hold to be lifted after the company had previously faced a rejection.
The U.S. Food and Drug Administration (FDA) has approved Hepcludex, developed by Gilead Sciences, for the treatment of chronic hepatitis D (HDV) in adults. The approval of Hepcludex marks a significant milestone in liver disease care, offering patients in the United States access to a therapy specifically designed to target chronic hepatitis D, one of the most severe forms of viral hepatitis.
Hepcludex Brings New Hope for Patients
Chronic hepatitis D is considered the most aggressive form of viral hepatitis. The disease occurs only in individuals who are already infected with hepatitis B because the hepatitis D virus relies on the hepatitis B virus to replicate. Patients with chronic hepatitis D face a significantly higher risk of severe liver complications, including cirrhosis, liver failure, and hepatocellular carcinoma. Despite its seriousness, treatment options have historically been limited, making new therapeutic approvals particularly important for the medical community.
Significance of the FDA Decision
The FDA’s decision reflects growing recognition of the need for innovative treatments targeting rare and underserved diseases. Regulatory approval was based on clinical evidence demonstrating meaningful antiviral activity and improvements in important disease markers. The decision also highlights ongoing efforts to accelerate access to therapies that address conditions with limited treatment alternatives.
