REP 2139 combined with peginterferon alpha in the treatment of patients with HBV/HDV co-infection

REP 2139 combined with peginterferon alpha in the treatment of patients with HBV/HDV co-infection.

Journal Guide:The new hepatitis B drug REP 2139 combined with peginterferon alpha has a good functional cure rate for patients with HBV/HDV co-infection.

82% of patients can get a functional cure for hepatitis D, and 45% of patients can get a functional cure for hepatitis B, and they have good durability during a follow-up of 3.5 years.

Editor’s note: Although there are many studies on new hepatitis B drugs in the world, most of them are in the early clinical stage, and the latest reports from the three major international liver disease conferences all show that new hepatitis B drugs are combined with existing drugs (nucleosides and/or polyethylene glycol interference There are more and more studies on element α).

The latest results of a nucleic acid polymer REP 2139-Ca combined with PEG IFNα in the treatment of patients with HBV/HDV co-infection, led by Canadian Replicor, showed that 82% of patients can get a functional cure for hepatitis D and 45% of patients can get Hepatitis B is functionally cured and has good persistence during a follow-up of 3.5 years.

Research method

The REP 301 study is an open-label, non-randomized study that included 12 newly-treated hepatitis B virus (HBV)/hepatitis D virus (HDV) co-infected patients and studied the nucleic acid polymer (REP 2139-Ca) single-drug sequence The safety and effectiveness of the combination of PEG IFNα (PEG IFNα) in the treatment of patients.

Previously disclosed research results have shown that patients with HBV/HDV co-infection have achieved high HDV RNA clearance and HBV HBsAg clearance / Serological conversion rate.

The REP301-LTF study is a long-term follow-up study. 11 of the 12 participants who completed the above treatment participated in the evaluation every 6 months, and were followed up for a total of 3.5 years.

The main efficacy indicators are safety and tolerability, and the secondary efficacy indicators are HBV virological control (HBV DNA ≤ 2000 IU/mL and ALT normalization), hepatitis B functional cure (HBV DNA below the detection limit, HBsAg <0.05 IU /mL), HBsAg seroconversion, and functional cure of D liver disease (HDV RNA is below the detection limit and ALT returns).

Research result

In the REP 301 study, 12 patients received REP 2139-Ca monotherapy for 15 weeks, followed by combined PEG IFNα therapy for 15 weeks, followed by PEG IFNα monotherapy for 33 weeks, followed by 24 weeks. A total of 11 patients participated in the REP301-LTF study.

01 REP 2139-Ca combined with PEG IFNα is safe for the treatment of patients with HBV/HDV co-infection

In the REP301-LTF study, 11 patients completed a 3.5-year follow-up. All patients had no serious adverse reactions, and some patients had reversible minor adverse reactions.

During the follow-up of all participants, no abnormal changes in liver (bilirubin, albumin and international standardized ratio), kidney, hematology or lipid function were observed. The liver stiffness value (LMS) of 5 participants (all obtained virological control or functional cure of hepatitis B and D) decreased or returned to normal.

02 REP 2139-Ca combined with PEG IFNα in the treatment of HBV/HDV co-infected patients has a functional cure rate of 82% and a durable rate of 78%

In the REP 301 study, at the end of treatment, 82% (9/11) of the patients obtained HDV RNA below the lower detection limit (hepatitis D was functionally cured).

At the end of the REP 301 study, 78% of patients (7/9) maintained a state of HDV RNA below the lower detection limit.

At the end of the REP301-LTF study, 100% (7/7) of the patients maintained a functionally cured state of hepatitis D.

03 REP 2139-Ca combined with PEG IFNα in the treatment of HBV/HDV co-infected patients has a functional cure rate of 45% and a durable rate of 80%

In the REP 301 study, 45% (5/11) of the participants achieved HBsAg <0.05 IU/mL during the treatment period, and 80% (4/5) of the patients maintained a functionally cured state during the follow-up period.

During the REP 301 and REP 301-LTF study, blood samples of patients with HBsAg <0.05 IU/mL were further analyzed by high-sensitivity HBsAg NEXT (analytical sensitivity of 0.005 IU/mL).

During the treatment period, the HBsAg of the 5 participants continued to be below 0.05 IU/mL. After the initial HBsAg test, these 5 patients maintained <0.005 IU/mL during the treatment period.

During the follow-up period, 60% (3/5) of the participants maintained HBsAg <0.005 IU/mL during the 3.5-year follow-up, and 1 participant (0.01-0.006) achieved HBsAg <0.005 IU/mL at the end of the follow-up.

After treatment with PEG IFNα, the anti-HBs of 5 participants increased rapidly. During REP 2139-Ca monotherapy, 81.8% (9/11) of patients HBsAg immune complexes (HBsAg ICs) decreased with the decrease of HBsAg. During the treatment with PEG IFNα, anti-HBs increased rapidly while HBsAg ICs remained unchanged Or increase slowly.

During the REP301-LTF study, 90.9% (10/11) patients had a decline in HBsAg ICs levels. The decrease or increase of HBsAg ICs was not significantly correlated with the acute increase of ALT during treatment.

04 The overall efficacy of REP 2139-Ca combined with PEG IFNα in the treatment of HBV/HDV co-infected patients with functional cure of hepatitis D is good

Among the 7 patients whose HDV RNA was consistently lower than the detection limit (hepatitis D functional cure), 3 patients received sustained HBV virological response, 4 patients received sustained hepatitis B functional cure, and these 4 patients received HBV RNA and HBcrAg remained below the lower limit of detection throughout the follow-up period.

Five patients continued to have HBV DNA below the lower detection limit and HBsAg <1 IU/mL. The HBcrAg of these 7 participants was always below the lower detection limit.

Expert’s comments:

With the rapid development of clinical cure for hepatitis B, in addition to exploring the optimal treatment plan of the existing drug combination, there are also many new anti-HBV drugs in the research and development stage.

The latest research results of new hepatitis B drugs released at the 2020 EASL annual meeting and AASLD annual meeting found that most new drugs are difficult to effectively reduce HBsAg levels, the clinical cure rate is not good, and most drugs are in the early stage of clinical research, and no drugs have entered clinical phase III .

Most new drugs are beginning to explore the combination of existing drug treatments in pursuit of a higher clinical cure rate.

The results of a phase II clinical study of REP2139/REP2165 combined with PEG IFNα and TDF in the treatment of chronic hepatitis B patients published on Gastroenterology recently showed that patients with chronic hepatitis B can obtain a clinical cure rate of up to 60%, which also makes REP drugs attract attention.

This study found that REP 2139-Ca combined with PEG IFNα in the treatment of patients with HBV/HDV co-infection also showed a good and long-lasting therapeutic effect.

We look forward to the emergence of more exciting results to help chronic hepatitis B truly move towards the era of comprehensive clinical cure while realizing the functional cure of hepatitis D.

(source:chinanet)

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