The addition of nucleic acid polymers to tenofovir disoproxil fumarate (TDF) + pegylated interferon α-2a (pegIFN) does not alter tolerability and increases rates of hepatitis B surface antigen (HBsAg) loss and HBsAg seroconversion, according to a study published in Gastroenterology.

The nucleic acid polymers, REP 2139 and REP 2165, are phosphorothioate oligonucleotides that have demonstrated similar antiviral effects in preclinical studies. Both nucleic acid polymers are formulated for use as magnesium (Mg) chelate complexes, which has previously been shown to improve the administration tolerability of nucleic acid polymers.

Researchers conducted an open-label, phase 2 study on the safety and efficacy of REP 2139 or REP 2165 combined with TDF + pegIFN in patients with negative chronic hepatitis B virus (HBV) infection who were negative for hepatitis B e antigen (HBeAg). Following 24 weeks of TDF therapy, 40 patients were randomly assigned to groups that received 48 weeks of experimental therapy (TDF + pegIFN + REP 2139-Mg or REP 2165-Mg) or 24 weeks of control therapy (TDF + pegIFN) followed by 48 weeks experimental therapy. Patients were then followed for a treatment-free period of 48 weeks.


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The researchers found that during the first 24 weeks of TDF and pegIFN administration, significantly higher percentages of patients in the nucleic acid polymers group had decreases in HBsAg to < 1 IU/mL and hepatitis B surface antigen (HBsAg) seroconversion. At the end of the study period, 17 participants who received the experimental therapy, and 19 participants in the control group demonstrated a reduction in HBsAg of > 1 log10. During 48 weeks of treatment-free follow up, virologic control persisted in 24 of 34 participants, 14 of whom demonstrated HBsAg below the lower limit of quantification. Functional cure was found in 28 of 36 participants, of whom 14 maintained functional cure and HBsAg seroconversion.

In terms of safety, the researchers noted transaminase flares > 3-times the upper limit of normal were observed in 6 of 20 patients in the control group and in 18 of 20 patients in the experimental group during the first 24 weeks. Through week 48 of TDF + pegIFN + nucleic acid polymers, transaminase elevations above baseline occurred in 38 of 40 participants who were otherwise asymptomatic; flares were most notable in both groups during the initial declines in HBsAg.

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The study authors concluded that, “In a phase 2 randomized trial, we found that addition of [nucleic acid polymers] to TDF + pegIFN did not alter tolerability and significantly increased rates of HBsAg loss and HBsAg seroconversion during therapy and functional cure after therapy.”

Disclosure: This clinical trial was supported by Replicor Inc. Please see the original reference for a full list of authors’ disclosures.

Reference

Bazinet M, Pântea V, Placinta G, et al. Safety and efficacy of 48 weeks REP 2139 or REP 2165, tenofovir disoproxil, and pegylated interferon alfa-2a in patients with chronic HBV infection naïve to nucleos(t)ide therapy [published online March 5, 2020]. Gastroenterology. doi:10.1053/j.gastro.2020.02.058