What you need to know
July 15 2026 | Stella Dlamini
The recent U.S. Food and Drug Administration (FDA) approval of Hepcludex (bulevirtide) marked a major breakthrough in the fight against hepatitis delta. Conservative estimates suggest that approximately 4% of people living with chronic hepatitis B in the United States (U.S.) are also infected with hepatitis delta [1]. This translates to about 80,000 people. For all these people, the drug’s approval represents the first time they can access an effective, FDA-approved treatment for their condition.
What is hepatitis delta?
Discovered nearly 50 years ago, hepatitis delta is a small virus that infects individuals who are living with hepatitis B, or those who acquire both the hepatitis B and hepatitis delta viruses at the same time. The virus is transmitted through exposure to the blood and body fluids of an infected person. Hepatitis delta infection causes the most severe form of viral hepatitis, often leading to rapid disease progression and significantly increasing the risk of severe liver injury and liver cancer if left untreated. In 2025, hepatitis delta was officially classified as a class I carcinogen to humans by the International Agency for Research on Cancer (IARC) [2], owing to its association with increased risk for liver cancer. This classification reflects years of advocacy and evidence showing that people living with hepatitis delta are two-to-six times more likely to develop liver cancer than people living with hepatitis B infection alone.
How does Hepcludex work?
Hepcludex is a viral entry inhibitor and the only FDA-approved treatment for chronic hepatitis delta. Rather than attacking the virus directly, it prevents hepatitis delta from entering liver cells by blocking special protein entry points (known as NTCP receptors) located on the surfaces of liver cells. By preventing new liver cells from becoming infected, the drug helps reduce viral replication and limits ongoing liver injury.
Hepcludex is approved for adults aged 18 and older without cirrhosis or those with compensated cirrhosis, a stage where the liver is injured but continues to retain its functions. Hepcludex is administered as a once-daily subcutaneous injection (injected into the fatty tissue under the skin), typically into the lower abdomen or upper thigh. After appropriate training from a health care professional, many individuals can safely self-administer the medication at home.
Gilead, the manufacturer of Hepcludex, advises that once treatment with Hepcludex has been started, it should not be stopped without first discussing it with a health care provider. Stopping treatment may increase the risk of a ‘flare-up’, where the virus may become active again.
What did clinical trials show?
The FDA approval was supported by Phase 3 clinical trials conducted across the U.S, Germany, Italy, Russia and Sweden.
48% of participants on Hepcludex experienced a significant decline in hepatitis delta viral load (or 2 log reduction in hepatitis delta RNA) and alanine aminotransferase (ALT) normalization, compared to just 2% in the group of participants who had treatment initiation delayed. Importantly, these outcomes were maintained for 144 weeks (approximately three years) for those who received early treatment [3].
While Hepcludex reduces the hepatitis delta viral load, it does not directly affect the hepatitis B viral load, so it is important to maintain standard care for hepatitis B infection when getting treatment for hepatitis delta.
What does this mean for people living with hepatitis B and delta?
Despite hepatitis delta being the most severe form of viral hepatitis, fewer than 11% of people living with chronic hepatitis B are estimated to have ever been tested for the virus in the U.S. [4]. Since hepatitis delta can only occur in people with hepatitis B, anyone living with chronic hepatitis B should discuss hepatitis delta testing with their health care provider. With effective treatment now available, there is a massive opportunity to get tested for hepatitis delta, identify infection and receive treatment early.
Individuals already diagnosed with hepatitis delta should speak with their health care provider to determine whether they are eligible for Hepcludex treatment. Gilead has a Support Path Program created to assist individuals with navigating insurance and financial support for accessing the treatment, including for eligible uninsured individuals.
What does this mean for health care providers?
The availability of an effective drug is also an opportunity to change the approach to hepatitis delta care in clinical practice. Health care providers should proactively identify patients at risk by testing all people living with hepatitis B for hepatitis delta. Hepatitis delta diagnostic capacity has expanded in the U.S., and tests are available to order from multiple labs. Providers should now also make efforts to ensure their eligible patients are started on Hepcludex as soon as possible.
Of course, vaccination against hepatitis B for those who are not infected remains a paramount preventative step, which ensures that individuals are protected from hepatitis B, without which hepatitis delta infection cannot occur.
This approval marks a significant change for everyone involved in hepatitis delta. The next challenge is ensuring that those who stand to benefit from this breakthrough are identified, diagnosed and connected to treatment with no delays. To learn more about hepatitis delta, please visit Hepatitis Delta Connect.
References:
1. Gish RG. Delta hepatitis in the United States: epidemiology, testing, and linkage to care. Gastroenterol Hepatol (N Y). 2023 Oct;19(10):603-605. PMID: 38404959; PMCID: PMC10882855.
2. World Health Organization. WHO urges action on hepatitis, announcing hepatitis D as carcinogenic [Internet]. Geneva: World Health Organization; 2025 Jul 28 [cited 2026 Jul 9]. Available from: https://www.who.int/news/item/28-07-2025-who-urges-action-on-hepatitis-announcing-hepatitis-d-as-carcinogenic
3. Gilead Sciences. FDA grants accelerated approval to Gilead’s Hepcludex® (bulevirtide-gmod), the first and only approved treatment for chronic hepatitis delta virus (HDV) [Internet]. Foster City (CA): Gilead Sciences; 2026 May 22 [cited 2026 Jul 9]. Available from: https://www.gilead.com/news/news-details/2026/fda-grants-accelerated-approval-to-gileads-hepcludex-bulevirtide-gmod-the-first-and-only-approved-treatment-for-chronic-hepatitis-delta-virus-hdv
4. B. V. John, M. M. Amoli, D. M. Evon, R. Wong, and B. Dahman, “Hepatitis Delta Testing Trends in a US National Cohort: An Analysis of Patient and Provider- Level Predictive Factors,” Hepatology Communications 8, no. 5 (2024): e0401.