Arbutus Biopharma presented updated data from its Phase 2a program for imdusiran on Nov. 12, reporting that 10 patients have achieved a functional cure of chronic hepatitis B and that most patients who stopped nucleoside therapy have remained off it for years. The presentation, filed with the Securities and Exchange Commission, says 89% of patients who stopped nucleoside analogue therapy in the company's two Phase 2a trials remain off it through up to 146 weeks of follow-up, more than three years. The company also said 46% of all Phase 2a patients, 48 of 105, achieved a functional cure or discontinued nucleoside therapy.
The data are cumulative, drawn from small, open-label trials with different regimens, and they come with the caveats that apply to any early-phase program. But they land at a moment when the field has a new reference point. Bepirovirsen, the first drug approved with a functional-cure claim in chronic hepatitis B, reached the U.S. market in October. Arbutus is arguing that its siRNA approach can produce durable cures with a better dosing schedule, and that the durability data are now long enough to matter.
The disease
Chronic hepatitis B affects about 240 million people worldwide, according to the company's presentation. It causes about 1.1 million deaths a year, mostly from cirrhosis and liver cancer. Nucleoside analogues suppress the virus but rarely eliminate it, and most patients have to take them for life. Pegylated interferon can produce a functional cure in a minority of patients, but it is poorly tolerated and many patients cannot finish the course.
A functional cure is defined as sustained loss of hepatitis B surface antigen and undetectable HBV DNA after all treatment stops, maintained for at least 24 weeks. It is not a sterilizing cure: the virus may still be present in the liver. But it is associated with a much lower risk of cirrhosis and liver cancer, and it lets patients stop daily therapy. That is why functional cure has become the goal of the field.
The approval of bepirovirsen changed the conversation. The drug, developed by GSK, is an antisense oligonucleotide given by injection. Its Phase 3 data showed a functional cure rate that was modest in absolute terms but clearly better than existing options, and the FDA accepted a definition that allows isolated "blips" in surface antigen or HBV DNA as long as they are not consecutive. Bepirovirsen was approved in the U.S. in October, according to the Arbutus presentation. The label carries a boxed warning for severe ALT flares and low platelets, and the drug requires frequent monitoring.
The data
Arbutus's imdusiran is a subcutaneous siRNA that targets HBV RNA. It is given every four, eight, or twelve weeks, and it is combined with an immunotherapeutic to try to wake up the immune system. In IM-PROVE I, the combination was imdusiran plus pegylated interferon and nucleoside therapy. In IM-PROVE II, it was imdusiran plus low-dose nivolumab and, in one group, VTP-300, an investigational immunotherapeutic from Barinthus.
The presentation counts 10 patients across the Phase 2a program who have achieved a functional cure; a long-term follow-up slide notes one additional patient who achieved a cure during follow-up. Of the eight who entered long-term follow-up, five, or 63%, maintained the cure. Three who lost the cure are partial cures, meaning their HBV DNA is below the limit of quantification and their surface antigen is below 100 IU/mL while off nucleoside therapy. One patient was not followed after 60 weeks.
The durability data are the most distinctive part. Arbutus says 16 of 18 patients, or 89%, who stopped nucleoside therapy in IM-PROVE I and II remain off it through up to 146 weeks. All 10 patients who achieved a functional cure continue to have HBV DNA below the limit of quantification. Separately, 56% of Phase 1b patients who elected to stop nucleoside therapy, five of nine, remained off all therapy for at least three years.
The company also applied the FDA's bepirovirsen definition, which allows isolated blips, to its own data. Under that definition, Arbutus says it would likely have achieved one more functional cure in IM-PROVE II, bringing the program's total to 11 across Phase 2a. That is a company analysis, not an FDA determination, but it shows how the regulatory definition can change the measured cure rate.
Safety looked manageable. More than 250 patients have received imdusiran across clinical trials. In patients receiving repeat doses, Arbutus reports no related serious adverse events and no safety-related discontinuations. ALT elevations occurred in 6% of patients, mostly Grade 1 or 2, and resolved; they tended to occur alongside declining surface antigen or markers of immune activation. The dosing interval of four to twelve weeks is less burdensome than daily pills or weekly interferon injections.
The caveats
The numbers are small. Ten functional cures across a program that has treated more than 250 patients is a meaningful signal, but it is not a validated cure rate. The trials are open-label, the regimens differ, and there is no control group. Some patients received pegylated interferon, which can produce functional cures on its own; others received nivolumab or VTP-300, which may contribute to the immune response. Untangling which component matters, and for whom, will require the Phase 2b program.
The patient populations also matter. The highest cure rates in IM-PROVE I were in patients with baseline surface antigen below 1,000 IU/mL, a group that tends to respond better to any therapy. Patients with higher antigen levels had lower rates. A cure that works best in patients with low antigen levels is still valuable, but it addresses a subset of the market, not all of it.
The durability data are encouraging but still maturing. Five of eight patients maintained a functional cure, and three lost it but remain off nucleoside therapy as partial cures. That is a better outcome than restarting daily therapy, but it is not the same as a cure. The follow-up is also company-reported and comes from a small number of patients. Arbutus has not run a randomized comparison, and the Phase 2b will be the first controlled test of whether the combination beats the standard of care.
The competitive picture
Bepirovirsen is the first approved product with a functional-cure claim, and it sets the bar. Its Phase 3 data and its boxed warning define the risk-benefit conversation for every competitor. Arbutus's argument is that imdusiran has a cleaner safety profile, a more convenient dosing schedule, and comparable or better durability in a subset of patients. That argument will be tested in Phase 2b, not in a press release.
Other companies are pursuing functional cures with different mechanisms, including therapeutic vaccines, checkpoint inhibitors, and combinations of siRNAs and immunotherapeutics. The field is crowded, and the standard of care is moving. Arbutus's advantage is that it has been in the clinic longer than most and has long-term follow-up that competitors may not yet have. Its disadvantage is that it is a small company with limited cash: $104.6 million as of Oct. 31, according to the presentation.
The regulatory path
Arbutus has FDA Fast Track designation for imdusiran, which it received in April 2026. The company says it is evaluating development plans for a Phase 2b trial and looking for ways to accelerate development. It has not announced a start date or a design.
The earlier Phase 2a data, covered by Contagion Live, showed a 50% functional-cure rate in patients with baseline surface antigen below 1,000 IU/mL in one cohort. The new presentation adds durability and long-term follow-up rather than a new topline. That distinction matters: the efficacy signal was already known, and what Arbutus is now trying to show is that the cures last.
The Phase 2b will need to show a clear, reproducible functional-cure rate in a defined population, with a safety database large enough to support approval. The FDA's acceptance of the bepirovirsen blip definition helps, because it gives the field a common way to measure cure. But the agency will still want to see durability and a benefit that justifies the risks of an injectable immunotherapy combination.
What to watch
The first thing to watch is the Phase 2b design. The patient population, the regimen, and the endpoint will determine whether Arbutus can replicate the Phase 2a signal. The second is financing. A Phase 2b trial in hepatitis B is expensive, and the company's cash position will shape how quickly it can move.
The third is the competition. If bepirovirsen's launch establishes a market and payers accept the monitoring burden, a better-tolerated alternative could find a path. If the market is slower to develop, Arbutus may need a partner. The fourth is the data. The next update on durability, and any new functional cures, will show whether the Phase 2a signal is holding.
For patients, the near-term change is not a new option yet. It is the prospect of a finite regimen that can stop the virus long enough to let people stop daily therapy. That is a meaningful goal, and the Arbutus data move it forward. But the numbers are still small, and the Phase 2b will decide whether the promise holds.
Primary sources
- Arbutus's Nov. 12 corporate presentation, filed as an exhibit to its Form 8-K, for the Phase 2a data, durability, safety, pipeline, and financial position.
- Arbutus's April 2026 press release on the FDA Fast Track designation for imdusiran.
- Contagion Live's coverage of the earlier imdusiran functional-cure data for context on the Phase 2a results.