BARACLUDE: Updates to Adverse Reactions from Long-Term Observational Study

BARACLUDE: Updates to Adverse Reactions from Long-Term Observational Study

November 8, 2019

FDA recently approved changes to the BARACLUDE® (entecavir) tablets and oral solution product labeling. The revisions are in response to a post marketing commitment related to a large simple safety study to assess the major clinical outcomes of death, progression of liver disease, and cancer in a broad population of HBV-infected patients using entecavir compared to standard of care over a period of 5 to 10 years of follow-up.

Section 6.2 Postmarketing Experience was updated to include the following Data from Long-Term Observational Study Study AI463080 was a randomized, global, observational, open-label Phase 4 study to assess long-term risks and benefits of BARACLUDE (0.5 mg/day or 1 mg/day) treatment as compared to other standard-of-care HBV nucleos(t)ide analogues in subjects with chronic HBV infection. A total of 12,378 patients were treated with BARACLUDE (n=6,216) or other HBV nucleos(t)ide treatment [non-entecavir (ETV)] (n=6,162). Patients were evaluated at baseline and subsequently every 6 months for up to 10 years. The principal clinical outcome events assessed during the study were overall malignant neoplasms, liver-related HBV disease progression, HCC, non-HCC malignant neoplasms, and death. The study showed that BARACLUDE was not significantly associated with an increased risk of malignant neoplasms compared to other standard-of-care HBV nucleos(t)ides, as assessed by either the composite endpoint of overall malignant neoplasms or the individual endpoint of non-HCC malignant neoplasms. The most commonly reported malignancy in both the BARACLUDE and non-ETV groups was HCC followed by gastrointestinal malignancies. The data also showed that long-term BARACLUDE use was not associated with a lower occurrence of HBV disease progression or a lower rate of death overall compared to other HBV nucleos(t)ides. The principal clinical outcome event assessments are as follows.

Limitations of the study included population changes over the long-term follow-up period and more frequent post-randomization treatment changes in the non-ETV group. In addition, the study was underpowered to demonstrate a difference in the non-HCC malignancy rate because of the lower than expected background rate.

The updated label will soon be available at Drugs@FDA or DailyMed

Kimberly Struble

Division of Antiviral Products

Food and Drug Administration

Elizabeth Thompson

Division of Antiviral Products

Food and Drug Administration

Michael Stanfield Jr.

Division of Antiviral Products

Food and Drug Administration