GSK enters agreement to obtain exclusive license for hepatitis B therapy to expand bepirovirsen development

JNJ-3989 is an investigational hepatitis B virus-targeted small interfering ribonucleic acid (siRNA) therapeutic that GSK intends to evaluate in a sequential regimen with bepirovirsen, GSK’s investigational antisense oligonucleotide, for the treatment of adult non-cirrhotic patients with chronic hepatitis B (CHB) on nucleos(t)ide analogue (NA) therapy.

There is high unmet need in CHB with an estimated 300 million people living with the disease and a less than 3-7% functional cure rate with current treatment options. Patients reach functional cure when the hepatitis B virus and viral proteins are at levels low enough to be undetectable in blood and can be controlled by the immune system without medication.

Bepirovirsen is the only single agent in phase III development that has shown clinically meaningful functional cure response for patients with CHB receiving oral NAs, following positive results demonstrated in the B-Clear and B-Sure clinical trials. B-Clear identified sub-groups of patients most likely to benefit from treatment with bepirovirsen, and also solidified bepirovirsen as a potential backbone therapy in future sequential regimens to pursue functional cure in additional patients with CHB.

Tony Wood, Chief Scientific Officer, GSK, said, “We are excited to build on promising results already demonstrated with bepirovirsen to investigate a novel sequential regimen with JNJ-3989. We believe this approach could redefine the treatment paradigm for chronic hepatitis B by helping even more patients achieve functional cure.”

Chris Anzalone, Ph.D., President and CEO of Arrowhead said, “GSK has a global reach, a clear commitment to help those living with chronic hepatitis B, and a promising strategy for clinical studies designed to improve functional cure rates. We have great confidence in the team at GSK and look forward to seeing this program progress towards the goal of potentially helping the millions of patients with chronic hepatitis B worldwide without adequate treatment options. We would also like to thank our colleagues at Janssen for the great progress they made with JNJ-3989, the investigational siRNA therapeutic that Arrowhead discovered and initially developed.”

JNJ-3989 has the potential to move immediately into a phase II sequential regimen trial with bepirovirsen beginning in 2024, further strengthening GSK’s late-stage pipeline of specialty medicines.

This transaction builds on GSK’s relationship with Arrowhead, following the 2021 exclusive license of GSK4532990 (ARO-HSD), an investigational oligonucleotide therapeutic targeting HSD17B13 as a potential treatment for patients with alcohol-related and nonalcohol related liver diseases. The exclusive license granted GSK rights to further develop and commercialise GSK4532990 outside of Greater China.

Upon closing of the transaction, GSK will assume rights and obligations of the existing license agreement between Janssen and Arrowhead, including all remaining financial obligations owed to Arrowhead for JNJ-3989 under the original agreement. GSK will be responsible for upfront and potential milestone-based payments to both Janssen and Arrowhead totalling approximately $1 billion. Janssen will continue to be responsible for the ongoing clinical trials of JNJ-3989 at its expense and GSK will be solely responsible for all future development and commercialisation activities. Additionally, Arrowhead will receive tiered royalties on net sales pursuant to the original agreement.

This transaction is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.