GSK and Ionis Report Positive Phase 3 Results for Bepirovirsen in Chronic Hepatitis B

New Hope for Patients Living with Chronic Hepatitis B

Chronic hepatitis B (CHB) remains one of the world's most challenging infectious diseases. While current treatments can help control the virus, most patients need to stay on therapy for life. Achieving a functional cure has remained difficult, with cure rates generally below 1%.

Now, positive Phase 3 results from two major clinical studies suggest that bepirovirsen may offer a new treatment approach for people living with chronic hepatitis B.

Ionis Pharmaceuticals and its development partner GSK recently announced encouraging findings from the Phase 3 B-Well 1 and B-Well 2 trials. The results were published in the New England Journal of Medicine and presented at the European Association for the Study of the Liver (EASL) Congress.

What Is Bepirovirsen?

Bepirovirsen is an investigational antisense oligonucleotide (ASO) therapy being developed for chronic hepatitis B.

GSK licensed the drug from Ionis Pharmaceuticals, and both companies have worked together on its clinical development.

The treatment is designed to target hepatitis B virus activity directly by reducing viral replication and lowering levels of hepatitis B surface antigen (HBsAg), an important marker of infection.

Researchers believe that reducing HBsAg levels may help the body's immune system regain control over the virus.

The Phase 3 B-Well Studies

The Phase 3 clinical program included two pivotal studies called B-Well 1 and B-Well 2.

The trials evaluated whether six months of treatment with bepirovirsen could help patients achieve a functional cure of chronic hepatitis B.

The studies successfully met their primary endpoints, delivering statistically significant results compared with placebo.

What Does Functional Cure Mean?

When discussing hepatitis B treatment, the term "functional cure" has a specific meaning.

A functional cure occurs when:

• Hepatitis B virus DNA remains undetectable

• Hepatitis B surface antigen (HBsAg) remains undetectable

• These results continue for at least six months after treatment has stopped

In simple terms, it means the patient's immune system is controlling the infection without the need for ongoing medication.

Strong Results Across the Overall Study Population

The combined analysis from both Phase 3 studies showed encouraging outcomes.

Among patients treated with bepirovirsen:

• 19% achieved a functional cure response

Among patients receiving placebo:

• No patients achieved a functional cure

These results demonstrate a significant improvement over current treatment outcomes and highlight the potential of bepirovirsen as a new therapeutic option.

Even Better Results in a Key Patient Group

One of the most important findings came from a specific group of patients who had hepatitis B surface antigen levels of 1000 IU/mL or lower at the start of treatment.

This group represents approximately 45% of diagnosed chronic hepatitis B patients worldwide.

In these patients:

• 26% achieved a functional cure after treatment with bepirovirsen

This higher response rate suggests that baseline HBsAg levels may help identify patients who are more likely to benefit from the therapy.

Long-Term Benefits After Treatment Stopped

Researchers also evaluated outcomes after patients had completed treatment.

An exploratory analysis found that:

• 49% of patients treated with bepirovirsen achieved HBsAg levels of 100 IU/mL or lower one year after treatment ended

Lower HBsAg levels are considered a positive sign because previous research has linked them to stronger immune control and improved long-term outcomes.

These findings suggest that the benefits of bepirovirsen may continue well beyond the treatment period.

Continued Suppression of Viral Activity

The studies also examined hepatitis B virus DNA levels after treatment completion.

At Week 72, which was approximately six months after treatment ended at Week 48:

• 23% of all treated patients maintained hepatitis B virus DNA levels below the lower limit of quantification

Among patients with baseline HBsAg levels of 1000 IU/mL or below:

• 31% maintained these low viral DNA levels

These results indicate that a meaningful number of patients continued to suppress viral activity long after therapy was completed.

Safety and Tolerability Findings

Safety remains an important consideration for any new treatment.

According to the Phase 3 studies, bepirovirsen demonstrated an acceptable safety and tolerability profile that was consistent with earlier clinical trials.

The most commonly reported side effects included:

• Injection site redness

• Injection site pain

• Temporary increases in liver enzyme levels

No unexpected safety concerns were reported during the studies.

Why These Results Matter

Current treatment options for chronic hepatitis B are effective at controlling viral replication, but they rarely provide a functional cure. As a result, many patients require lifelong treatment and monitoring.

The Phase 3 findings suggest that bepirovirsen may help address this unmet need by:

• Reducing hepatitis B virus replication

• Lowering hepatitis B surface antigen levels

• Supporting immune system control of the infection

• Increasing the possibility of achieving a functional cure

If future regulatory reviews are successful, bepirovirsen could become an important new option for patients seeking treatment beyond long-term viral suppression.

Looking Ahead

The positive Phase 3 results from the B-Well 1 and B-Well 2 trials represent a significant milestone for both GSK and Ionis Pharmaceuticals.

With meaningful functional cure rates, durable viral suppression, and a manageable safety profile, bepirovirsen has demonstrated strong potential as a next-generation therapy for chronic hepatitis B.

As the global healthcare community continues searching for more effective ways to manage and potentially cure hepatitis B, these results provide encouraging evidence that a functional cure may be achievable for a meaningful proportion of patients in the future.