In a significant development for the treatment of chronic hepatitis B (CHB), GSK plc (LSE/NYSE: GSK) has announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to bepirovirsen, an investigational antisense oligonucleotide (ASO). This milestone is a testament to the potential of bepirovirsen in addressing the unmet medical needs of CHB, a serious condition that affects nearly 300 million people worldwide.

Fast Track designation is a critical step in the development process, designed to facilitate the development and expedite the review of drugs that target serious conditions and fill an unmet medical need. The FDA’s decision was influenced by data from the phase IIb trials, B-Clear and B-Sure, which demonstrated the efficacy, safety, and durability of response of bepirovirsen in individuals with CHB. The ongoing confirmatory phase III programme, B-Well, further underscores the commitment to bringing this innovative treatment to patients.

CHB remains a life-threatening condition, with current treatments offering a functional cure rate of less than 2-8%, which is not clinically meaningful. A functional cure is defined as the point when the hepatitis B virus DNA and viral proteins are undetectable in the blood and can be controlled by the immune system without medication. The existing oral antiviral therapies, known as nucleoside/nucleotide analogues (NAs), only suppress the virus without directly lowering hepatitis B surface antigen (HBsAg), which is crucial for achieving a functional cure.

Bepirovirsen stands out as the only single agent in phase III development showing the potential to achieve a clinically meaningful functional cure response when combined with oral NAs. This potential was highlighted by positive results in the B-Clear and B-Sure clinical trials, with B-Clear indicating that patients with low baseline hepatitis B surface antigen levels are most likely to benefit from bepirovirsen treatment. The investigational ASO is also being explored as a cornerstone therapy in future sequential regimens aimed at functional cure in a broader CHB patient population.

The triple-action mechanism of bepirovirsen, designed to recognize and destroy the hepatitis B virus’s genetic components, offers a novel approach to treatment. By inhibiting viral DNA replication, suppressing HBsAg levels, and stimulating the immune system, bepirovirsen represents a significant advancement in the pursuit of a durable and sustained response for CHB patients.

Discovered and jointly developed with Ionis Pharmaceuticals, bepirovirsen (formerly known as ‘ISIS 505358 or IONIS-HBVRX’) is a product of the ASO HBV programme in-licensed by GSK from Ionis Pharmaceuticals in August 2019. This collaboration highlights the importance of partnerships in advancing healthcare innovations.

The FDA’s Fast Track designation for GSK’s bepirovirsen marks a pivotal moment in the fight against chronic hepatitis B. By focusing on a solution that goes beyond viral suppression to achieve a functional cure, bepirovirsen represents a beacon of hope for millions suffering from this condition. This development not only underscores the potential of antisense oligonucleotides in treating viral infections but also sets a new standard for collaborative efforts in pharmaceutical research and development.

  antisense oligonucleotide, bepirovirsen, chronic hepatitis B, GSK, Ionis Pharmaceuticals, US FDA, USA