FDA Approves Bepirovirsen: Why Oligonucleotide CDMOs Should Take Note

The FDA has approved Hibsago (bepirovirsen), GSK's antisense oligonucleotide, for chronic hepatitis B (CHB) virus infection in combination with nucleos(t)ide analogue therapy.¹ The indication covers adults without cirrhosis who have received nucleos(t)ide analogue therapy for at least 6 months, have suppressed viral DNA, and have hepatitis B surface antigen (HBsAg) levels of 3000 IU/ml or lower, as determined by an FDA-authorized test. The agency granted the approval under priority review and Breakthrough Therapy Designation.

Unlike current antivirals, which many patients take indefinitely, bepirovirsen is given as a 6-month course, with the option to self-administer after the first dose.¹

“Despite current therapies, many people living with chronic hepatitis B remain on treatment indefinitely and continue to face the risk of serious liver complications. For the first time, with Hibsago, US patients have the potential to achieve functional cure after a 6-month treatment course, with the added convenience of the option of self-administration after the first dose,” said Tony Wood, chief scientific officer, GSK, in a press release.¹

What Did the Phase III Trials Show?

The approval rests on the B-Well 1 and B-Well 2 trials, randomized, double-blind, placebo-controlled studies run in 29 countries.¹ In pooled data, 19% of patients treated with bepirovirsen achieved functional cure (233 of 1220), compared with none of 614 patients on placebo. Standard of care alone typically achieves a functional cure rate below 1% after 1 year. Functional cure is defined as undetectable viral DNA and HBsAg for at least 24 weeks after all treatment stops.

In a key secondary end point, the functional cure rate reached 26% (200 of 768 vs 0 of 393) among patients with baseline HBsAg of 1000 IU/ml or lower, a group GSK estimates represents approximately 45% of diagnosed cases globally.¹ In exploratory analyses, 49% of patients in the overall population reached HBsAg of 100 IU/ml or lower by week 72. The most common adverse events were injection site erythema, local pain, and a temporary rise in a liver enzyme.

“This is the start of a new era in treating people living with CHB. Bepirovirsen offers patients the potential to achieve functional cure after a short period of treatment, a long-standing goal for patients and physicians alike,” said Dr Norah Terrault, chief of gastroenterology and hepatology, the Keck Medical Center of the University of Southern California, in the press release.¹

Bepirovirsen is designed to inhibit production of viral RNA, lowering viral proteins and HBsAg in the blood and potentially helping the immune system regain control.¹

Why Does This Approval Matter?

The approval moves antisense oligonucleotides beyond the rare disease indications where the modality has mostly been commercialized and into a chronic infection that affects approximately 1.7 million people in the US and more than 240 million worldwide.¹ That shift will test solid-phase synthesis, purification, and analytical capacity at commercial scale. A finite 6-month course also changes demand forecasting: supply will depend on how many new patients start treatment rather than on lifelong maintenance dosing.

CDMOs with oligonucleotide capabilities may see more inquiries as similar programs advance.¹ Saharsh Davuluri, CEO, Neuland Labs, claimed that CDMOs must become more agile as synthetic modalities such as peptides expand into new therapeutic areas.

Self-administration after the first dose also puts weight on presentation design, instructions for use, and patient handling.¹ Expedited pathways like the one bepirovirsen used tend to compress chemistry, manufacturing, and controls (CMC) timelines.

Eligibility also depends on quantitative HBsAg testing, so diagnostics availability will help determine uptake.¹ GSK said it expects further regulatory decisions in other regions in the coming months.

What Production Hurdles Could GSK Face?

Scaling an antisense oligonucleotide like bepirovirsen carries a heavy material burden.² In a 2021 Journal of Organic Chemistry perspective led by a GSK process chemist, members of the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable reported process mass intensities averaging 4299 across 8 development-stage processes. That means roughly 4300 kilograms of raw materials per kilogram of drug substance, vs a median of 168-308 for small molecules. Synthesis and purification generate most of that waste, with detritylation alone consuming nearly half of synthesis-stage materials. The authors also flagged lyophilization, which can take several days, as a key throughput bottleneck for commercial supply.

References

1. GSK. Hibsago (bepirovirsen) approved in the US for the treatment of chronic hepatitis B (CHB). News release. October 20, 2026. Accessed October 21, 2026. View source

2. Andrews BI, Antia FD, Brueggemeier SB, et al. Sustainability challenges and opportunities in oligonucleotide manufacturing. J Org Chem. 2021;86(1):49-61. doi:10.1021/acs.joc.0c02291 View source