Arbutus' Imdusiran and VTP-300 Treatment Significantly Lowers HBsAg Levels

Arbutus Biopharma Corporation, a clinical-stage biopharmaceutical firm specializing in virology to tackle chronic hepatitis B virus (cHBV) infection, has announced encouraging preliminary end-of-treatment (EOT) data from its Phase 2a clinical trial, IM-PROVE II (AB-729-202). The trial assessed the effects of imdusiran, Arbutus’ RNAi therapeutic, combined with Barinthus Biotherapeutic's T-cell stimulating immunotherapeutic, VTP-300, in patients already on standard nucleos(t)ide analogue (NA) therapy. The findings were revealed by Dr. Kosh Agarwal during a session at the European Association for the Study of the Liver (EASL) Congress.

IM-PROVE II enrolled 40 patients with stable NA therapy, who were administered imdusiran (60mg every 8 weeks) for 24 weeks. After this period, they were randomized to receive either VTP-300 or a placebo at Weeks 26 and 30. The trial data demonstrated significant reductions in HBsAg levels during the imdusiran phase, with 95% of patients achieving HBsAg levels below 100 IU/mL by Week 26.

At 24 weeks post-EOT, patients in the treatment arm showed significantly lower HBsAg levels compared to the placebo group. Specifically, 94% of patients in the treatment group achieved HBsAg levels less than 100 IU/mL, and 36% had levels below 10 IU/mL at EOT (Week 48). In contrast, the placebo group had 84% and 21% of patients reaching these thresholds, respectively. At 24 weeks post-EOT, 80% of the treatment group maintained HBsAg levels under 100 IU/mL, compared to 16% in the placebo group.

Furthermore, 84% of the treatment group met criteria to discontinue NA therapy after Week 48, whereas only 53% of the placebo group did. One patient in the treatment arm achieved undetectable HBsAg levels, and another experienced a significant decline during the NA-therapy discontinuation follow-up.

The safety profile of the combined imdusiran and VTP-300 treatment was favorable, with no serious adverse events or treatment discontinuations. Common adverse events included injection site reactions and transient ALT increases.

Dr. Agarwal highlighted the significant impact of imdusiran and VTP-300 on reducing HBsAg levels, emphasizing the proportion of patients eligible to stop NA therapy in the treatment arm. Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma, noted the consistent HBsAg reductions with imdusiran, suggesting potential enhancements in response rates when combined with immunomodulatory therapies like VTP-300.

Arbutus Biopharma remains optimistic about their approach in lowering surface antigen to promote HBV-specific immune responses. They anticipate additional data from a trial arm evaluating the efficacy of nivolumab, a PD-1 monoclonal antibody, in enhancing treatment responses.

The IM-PROVE II trial initially enrolled 40 non-cirrhotic, virally suppressed cHBV patients on stable NA therapy who were administered imdusiran for 24 weeks. Those meeting specific criteria after the 48-week period discontinued NA therapy and were followed up for 48 additional weeks. An amendment to the trial includes an extra cohort of 20 patients receiving imdusiran plus NA therapy for 24 weeks, followed by VTP-300 and nivolumab. Preliminary data from this cohort are expected in the latter half of 2024.

Imdusiran (AB-729) is an RNA interference therapeutic aimed at reducing all HBV viral proteins and antigens, crucial for reawakening the immune system to combat HBV. Utilizing Arbutus’ GalNAc delivery technology, imdusiran is designed for subcutaneous delivery and has shown meaningful reductions in HBsAg and HBV DNA in clinical trials. It is currently being evaluated in multiple Phase 2a trials.

Chronic hepatitis B is a significant health concern, affecting over 250 million people globally and causing approximately 820,000 deaths annually due to complications like cirrhosis and liver cancer. Arbutus Biopharma is focused on developing a functional cure for cHBV, leveraging a combination of novel therapeutics to suppress HBV DNA, reduce surface antigen, and boost immune responses. Their pipeline includes imdusiran and an oral PD-L1 inhibitor, AB-101, with both showing promising clinical data.

Arbutus’ approach involves ongoing research and clinical trials to refine and enhance their treatment strategies, aiming ultimately to provide a functional cure for cHBV patients worldwide.