Arbutus Achieves Milestone In HBV Treatment By Combination Of Imdusiran And Interferon

Arbutus Biopharma Corporation, a clinical-stage biopharma firm specializing in virology and aiming to deliver a functional cure for chronic hepatitis B virus (cHBV), has unveiled new findings from its IM-PROVE I Phase 2a trial (AB-729-201). The trial evaluated the RNAi candidate imdusiran combined with pegylated interferon alfa-2α (IFN) alongside ongoing nucleos(t)ide analogue (NA) therapy. Results indicate a 50% functional cure rate (3 out of 6 patients) among HBeAg-negative participants with baseline HBsAg levels under 1000 IU/mL and an overall cure rate of 25% (3 out of 12 participants).

“We are extremely excited to have functionally cured these patients with the imdusiran and interferon treatment regimen. There is a significant need for a functional cure for the more than 250 million patients chronically infected with HBV worldwide. Excess surface antigen production is believed to contribute to host immune exhaustion, resulting in inadequate immune response and failure to suppress the virus. These data support our belief that lowering surface antigen with imdusiran and incorporating an immunomodulator in the treatment regimen provides a functional cure in some patients with cHBV. We thank all the patients and investigators who participated in this clinical trial,” commented Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma.

The following essential information about patients in Cohort A1 who received imdusiran add-on 24 weeks of IFN, receiving associated NAs therapy is given below:

• 50% of patients (3/6) with baseline HBsAg <1000 IU/mL achieved functional cure by HBsAg loss with persistence plus HBV DNA less than LLOQ 24 weeks off of all treatments, including NAs, either with or without anti-HBs.

  
  

• Overall, 25% of patients achieved a functional cure.

  
  

• All of these patients who were functionally cured were also seroconverted, and anti-HB levels increased with the loss of HBsAg in the patients.

  
  

• The combination of imdusiran and IFN was generally safe and well tolerated. No related SAEs due to imdusiran or IFN were experienced, nor did any SAE lead to discontinuation.

  
  

Available on the Company's website, the late-breaker poster, titled, "IM-PROVE I: Imdusiran in Combination with Short Courses of Pegylated Interferon Alfa-2a in Virally Suppressed, HBeAg Negative Subjects with Chronic HBV (cHBV) Infection Leads to Functional Cure", reports results for the entire data set of patients dosed in this clinical trial for all four cohorts.

Dr. Emily Thi, Senior Director of Immunobiology and Biomarkers Research at Arbutus Biopharma, will also present additional immune activation data of those patients in Cohort A1 that achieved a functional cure in a poster titled: "Soluble Immune Biomarker Profiling of Chronic Hepatitis B Subjects Treated with Imdusiran in Combination with Pegylated Interferon Alfa Reveals Phases of Immune Activation." 

This poster will show that patients in Cohort A1 experienced far more significant increases of favorable immune biomarkers compared with the other cohorts. Functionally cured patients and patients with baseline HBsAg < 1000 IU/mL had elevations of key immune biomarkers during the imdusiran lead-in, IFN treatment, and follow-up periods, suggesting immune activation induced by imdusiran plus IFN treatment.

Professor Man-Fung Yuen, D.Sc., M.D., PhD, Chief of the Division of Gastroenterology and Hepatology, the University of Hong Kong and Principal Investigator of the IM-PROVE I clinical trial, who will present the data at AASLD, said in a statement, “While 48 weeks of interferon can be used as a standard of care treatment for HBV patients, historically, less than 10% of patients experience a functional cure. Here, with the combination of imdusiran and 24 weeks of interferon, we see a 50% functional cure rate in HBV patients with HBsAg less than 1000 IU/mL at baseline and a 25% functional cure rate overall.”

He further added, “In addition, I was pleased to see that this regimen with a short course of interferon was generally safe and well-tolerated. These data are extremely impressive and provide hope for the millions of HBV patients worldwide and the medical community that a finite curative treatment is possible with imdusiran and interferon. For the first time, we are seeing a meaningful percentage of HBV patients functionally cured with an RNAi therapeutic and interferon.”