Arbutus’ Imdusiran with Short Course Interferon Achieves Sustained Undetectable HBsAg, a Necessity for HBV Functional Cure

At the end of treatment, 33.3% of patients receiving imdusiran for 48 weeks, interferon (IFN) for 24 weeks and ongoing nucleoside analogue (NA) therapy achieved undetectable levels of HBsAg that were maintained in 100% of these patients 24 weeks after completing imdusiran and IFN treatment

Of the patients who have stopped all therapy, six still have undetectable levels of HBsAg and HBV DNA, with two of these patients reaching 12 weeks off all therapy

All six patients have seroconverted and have high titers of anti-HBsAg antibodies

These new Phase 2a data were presented at the European Association for the Study of the Liver (EASL) Congress 2024

WARMINSTER, Pa., June 05, 2024 (GLOBE NEWSWIRE) -- Arbutus Biopharma Corporation (Nasdaq: ABUS) (“Arbutus” or the “Company”), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop a functional cure for people with chronic hepatitis B virus (cHBV) infection, today announced new data from its Phase 2a clinical trial IM-PROVE I (AB-729-201) showing that imdusiran, the Company’s RNAi therapeutic, and 24 weeks of pegylated interferon alfa-2α (IFN), a standard-of-care immunomodulator, added to ongoing nucleos(t)ide analogue (NA) therapy, reduced HBsAg levels and led to sustained HBsAg loss in some patients with cHBV during and after treatment. These data were presented today in the Viral Hepatitis B and D: New therapies, unapproved therapies or strategies poster session, and will be featured during a poster tour on Thursday, June 6, 2024, at the European Association for the Study of the Liver (EASL) Congress.

Select key data from this Phase 2a clinical trial include:

• Some patients who received either 48 or 24 weeks of imdusiran and 24 weeks of IFN with their ongoing NA therapy achieved undetectable HBsAg at the end-of-treatment (EOT) (33.3%, n=4/12; and 23.1%, n=3/13, respectively) that was sustained 24 weeks after completing imdusiran and IFN treatment (33.3%, n=4/12 and 15.4%, n=2/13, respectively). All six patients with sustained HBsAg loss have seroconverted with high anti-HBsAg antibody levels (43.8 to >1,000 mIU/mL suggestive of immune control) and are being followed for maintenance of both undetectable levels of HBsAg and HBV DNA for 24 weeks while off all therapy to assess for a functional cure.
• Two of the six patients have reached 12 weeks off all therapy while maintaining both undetectable levels of HBsAg and HBV DNA. The remaining four patients are at various timepoints less than 12 weeks off therapy with undetectable levels of HBsAg and HBV DNA.
• A total of 21 patients from across the four treatment cohorts have discontinued all therapy and are in the follow-up period. One patient that received 12 weeks of IFN treatment with imdusiran and NA therapy has maintained undetectable levels of HBsAg and HBV DNA while off all therapy for six months, thereby achieving a functional cure.

“These data are impressive with robust HBsAg response rates that are sustained after end-of-treatment in patients receiving imdusiran and IFN,” commented Professor Man-Fung Yuen, D.Sc., M.D., Ph.D., Chief of the Division of Gastroenterology and Hepatology, the University of Hong Kong, who presented the data at the Congress. “Unlike other RNAi candidates in development that have been evaluated in combination with IFN, in this trial, imdusiran was administered less frequently, at a lower dose, and when combined with a shorter 24-week course of IFN, achieved undetectable HBsAg that is sustained after end of treatment and into early off-treatment follow-up. This trial evaluated small groups of patients, yet there is reason to believe that the combination of imdusiran and IFN could potentially lead to a functional cure in those patients that remain off all therapy. These data are extremely important for the HBV community, and I look forward to continuing to follow the patients who have discontinued all treatment.”

To confirm undetectable HBsAg measured by the trial assay (lower limit of quantitation of 0.05 IU/mL), the Abbott HBsAg Next Qualitative assay, an ultrasensitive, research use only assay with a detection limit of 0.005 IU/mL, was utilized.  The Next Assay confirmed HBsAg loss in six of the seven patients at EOT, and those six maintained HBsAg loss for 24 weeks after completing imdusiran and IFN treatment.

These data from the IM-PROVE I trial suggest that the combination of imdusiran and 24 weeks of IFN was generally safe and well-tolerated. There were no serious adverse events (SAEs) related to imdusiran or IFN, and no adverse events (AEs) leading to discontinuation. The most common imdusiran-related treatment emergent adverse events (TEAEs) were transient ALT elevations and injection site bruising. The IFN-related TEAEs were consistent with the known safety profile of IFN.

“There is a significant need for a functional cure for the more than 250 million patients chronically infected with HBV worldwide,” commented Dr. Karen Sims, Chief Medical Officer of Arbutus Biopharma. “These data further support our belief that lowering surface antigen with imdusiran and incorporating an immunomodulator in the treatment regimen has the potential to provide a functional cure for patients with cHBV. We look forward to following the progress of these patients as well as those in our other Phase 2a trials evaluating imdusiran with other immunomodulators.”

The poster that was presented at EASL Congress 2024 can be accessed through the Arbutus website under Publications.

IM-PROVE I Trial Details

The IM-PROVE I Phase 2a clinical trial (AB-729-201; NCT04980482) enrolled 43 HBeAg-negative, NA-suppressed patients with cHBV infection. After a 24-week lead-in with imdusiran (60 mg every 8 weeks) added to ongoing NA therapy, patients were randomized into one of the following four cohorts:

A1: Imdusiran + NA + IFN weekly for 24 weeks (n=12)

A2: NA + IFN weekly for 24 weeks (n=13)

B1: Imdusiran + NA + IFN weekly for 12 weeks (n=8)

B2: NA + IFN weekly for 12 weeks (n=10)

After completion of the IFN treatment period (Week 52 for cohorts A1 and A2 and Week 40 for cohorts B1 and B2), patients underwent a 24-week follow-up period on NA therapy alone and were then assessed for discontinuation of NA therapy. Patients with ALT levels less than two times the upper limit of normal, undetectable HBV DNA, and HBsAg