Arbutus' Imdusiran with Interferon Achieves Sustained HBsAg Loss, Key for HBV Cure

Arbutus Biopharma Corporation, a clinical-stage biopharmaceutical firm, has announced promising new data from its Phase 2a clinical trial, IM-PROVE I (AB-729-201). The trial is investigating the effectiveness of imdusiran, Arbutus' RNA interference (RNAi) therapeutic, combined with pegylated interferon alfa-2α (IFN) and ongoing nucleos(t)ide analogue (NA) therapy in treating chronic hepatitis B virus (cHBV) infection. The latest findings were shared at the European Association for the Study of the Liver (EASL) Congress 2024.

Primary data from the trial indicate that imdusiran, when paired with IFN for 24 weeks, successfully reduced hepatitis B surface antigen (HBsAg) levels in some patients. Specifically, following treatment with imdusiran for either 24 or 48 weeks and 24 weeks of IFN, a subset of patients achieved undetectable levels of HBsAg by the end of the treatment period. For those receiving 48 weeks of imdusiran, 33.3% had undetectable HBsAg levels, while 23.1% of those on a 24-week regimen achieved the same result. Remarkably, these undetectable HBsAg levels were sustained in 33.3% and 15.4% of the respective groups 24 weeks post-treatment.

Notably, six patients who ceased all therapy maintained undetectable HBsAg and hepatitis B virus (HBV) DNA levels, with two of these patients maintaining these levels for 12 weeks off therapy. All six patients have seroconverted, displaying high levels of anti-HBsAg antibodies, suggesting immune control. The trial's outcomes were highlighted in a poster session at the EASL Congress, underscoring the potential of this therapeutic approach.

The IM-PROVE I trial enrolled 43 HBeAg-negative, NA-suppressed patients with cHBV infection. Patients were randomized into four cohorts after a 24-week lead-in with imdusiran. The cohorts evaluated combinations of imdusiran, NA, and IFN therapies for different durations. One cohort saw a patient maintain undetectable HBsAg and HBV DNA levels for six months off all therapy, achieving what is considered a functional cure.

Professor Man-Fung Yuen of the University of Hong Kong, who presented the data, praised the robust and sustained HBsAg response rates observed in the trial. He noted that imdusiran, administered less frequently and at a lower dose compared to other RNAi candidates, achieved lasting undetectable HBsAg levels when combined with a shorter 24-week IFN course. This suggests that the combination has the potential to lead to a functional cure for chronic HBV.

The trial also demonstrated that the combination of imdusiran and IFN was generally safe and well-tolerated. There were no serious adverse events (SAEs) related to the treatments, and no adverse events (AEs) led to discontinuation. Common adverse events included transient ALT elevations and injection site bruising for imdusiran, with IFN-related events aligning with its known safety profile.

Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma, emphasized the significant unmet need for a functional cure for the over 250 million patients globally affected by chronic HBV. She expressed optimism that the combination therapy could offer a viable solution and looked forward to further trial progress.

The trial utilized the Abbott HBsAg Next Qualitative assay, an ultrasensitive test, to confirm undetectable HBsAg levels. This assay reinforced the findings at the end-of-treatment, affirming the sustained HBsAg loss in six patients 24 weeks post-treatment.

In conclusion, the IM-PROVE I trial results from Arbutus Biopharma offer promising evidence that combining imdusiran with IFN and NA therapy could lead to sustained HBsAg loss and potentially a functional cure for chronic HBV. The ongoing monitoring and follow-up of patients will be crucial to further validate these findings and their long-term implications.