On Wednesday, pharmaceutical leaders GSK Plc (NYSE:GSK) and Ionis Pharmaceuticals Inc. (NASDAQ:IONS) unveiled promising results from their collaborative clinical development program for bepirovirsen, a novel antisense oligonucleotide therapy intended for chronic hepatitis B (CHB). The announcement followed the completion of two pivotal Phase 3 trials, named B-Well 1 and B-Well 2, comprising a combined patient population exceeding 1,800 individuals diagnosed with CHB.
Bepirovirsen, licensed by GSK from Ionis in 2019, represents an investigational treatment leveraging antisense technology to target hepatitis B viral RNA. The two companies have jointly advanced the drug’s clinical evaluation, aiming to address the substantial global health burden posed by CHB, which currently affects over 250 million people and remains the leading cause of liver cancer worldwide.
The B-Well trials successfully reached their primary endpoint, demonstrating that patients receiving bepirovirsen in conjunction with standard of care developed significantly higher rates of functional cure compared to those receiving standard care alone. "Functional cure" is a clinical benchmark indicating substantial and sustained loss of hepatitis B surface antigen (HBsAg), a key indicator signaling effective viral control and improved clinical prognosis.
The statistically robust efficacy was consistent across multiple ranked endpoints within the trials. Notably, patients presenting with lower baseline levels of HBsAg (≤1000 IU/ml) exhibited an even more pronounced therapeutic benefit, underscoring the potential of bepirovirsen to achieve impactful outcomes within specific patient subgroups.
In terms of safety, bepirovirsen was generally well tolerated, with an adverse event profile aligned with observations from earlier clinical investigations. No new safety signals emerged in this large patient cohort, supporting the drug’s suitability for further clinical development and eventual regulatory assessment.
The comprehensive trial data will be compiled and submitted for presentation at upcoming scientific congresses and prepared for publication in peer-reviewed medical journals. These full detailed results will also underpin regulatory submissions to healthcare authorities worldwide, anticipated in the first quarter of 2026.
GSK and Ionis envision bepirovirsen as potentially the first finite-duration, six-month treatment alternative for chronic hepatitis B, addressing a currently unmet clinical need for therapies offering a defined course rather than indefinite treatment. Furthermore, its mechanism and efficacy could support its use as a foundational backbone in future sequential therapeutic strategies designed to improve long-term patient outcomes.
Financially, the partnership includes upfront and license fees received by Ionis, supplemented by development milestone payments. Additionally, Ionis is eligible to receive up to $150 million in regulatory and sales milestones, alongside tiered royalty payments ranging from 10-12% on net sales of bepirovirsen, reflecting a shared commercial interest in the drug’s future market performance.
Industry analysts have responded favorably to this clinical progress. William Blair highlighted Ionis's strong start as it anticipates five Phase 3 data releases in 2026, pointing to bepirovirsen’s promising position. Analyst Myles Minter noted that bepirovirsen might represent an underappreciated therapeutic opportunity when compared to current market standards, citing Gilead Sciences Inc.’s (NASDAQ:GILD) Vemlidy product, which is projected to surpass $1 billion in fiscal 2025 revenues with steady growth of 11% year-over-year.
William Blair maintains an Outperform rating on Ionis, emphasizing the importance of reviewing the full dataset to comprehensively understand bepirovirsen’s clinical and safety profile.
In a separate but related development, Ionis Pharmaceuticals previously disclosed results from Phase 3 CORE and CORE2 studies evaluating olezarsen, another agent targeting severe hypertriglyceridemia (sHTG). These studies demonstrated a substantial, highly statistically significant placebo-adjusted mean reduction in fasting triglyceride levels of up to 72% at six months, reinforcing Ionis’s strong presence in innovative therapeutic areas.
At the time of reporting, Ionis Pharmaceuticals shares were trading up by 4.06% to $84.80, while GSK shares increased 1.20% to $51.16, reflecting investor optimism fueled by these clinical developments.