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P1101 in HCV Phase III in Genotype 2 Study (A14-301)

Background

Chronic HBV infections affect more than 200 million people worldwide. The hepatitis B virus (HBV), an enveloped DNA containing virus that replicates by reverse transcription. Based on DNA sequence comparison, HBV is classified into eight genotypes (A-H). Each genotype has a distinct geographic distribution. Genotype A is prevalent in Europe, Africa and South-east Asia, including the Philippines. Genotype B and C are predominant in Asia, genotype D is common in the Mediterranean area, the Middle East and India, genotype E is localized in sub-Saharan Africa and genotype F (or H) is restricted to Central and South America. All these genotypes can be identified in the United States. Chronic HBV infection is characterized by four phases including immune-tolerant phase, immune clearance, inactive carrier state, and reactivation. Not everyone will experience all four phases, and the lengths of the phases vary among people. Chronic HBV infection has been the major cause of liver cirrhosis and hepatocellular carcinoma (HCC), affecting people in Asia, Africa and the Middle East.

Unmet Medical Needs

The prevalence of chronic HBV infection varies widely in different parts of the world. In Taiwan, prevalence of HBV was 10-15% and approximately 2.5 -3.0 million HBsAg carriers. In US, it was estimated that 5.1% of population (0.8 - 1.4 million) had been exposed to HBV. Current guidelines recommend treatment for HBeAg-positive or HBeAg-negative patients with ALT >2X upper limit of normal (ULN) and HBV DNA >20,000 IU/mL. HBV DNA suppression, loss of HBeAg or HBsAg with or without seroconversion play a prominent role in decision making regarding the success and duration of antiviral therapy. Currently, several medications are approved for treatment of chronic HBV infection including pegylated interferon-alpha and nucleos(t)ide analogues (Lamivudine, Telbivudine, Entecavir, Adefovir, Tenofovir). However, current therapeutic options do not eradicate HBV infection in a high successful rate, since HBV remains either integrated in the host genome or in the nuclei of hepatocytes as covalently closed circular DNA (cccDNA). Virological relapse and clinical flares happens after patients ceased nucleos(t)ide analogues therapy.

Incentive of The Trial

In HBeAg positive patients, HBeAg seroconversion is an important outcome. Pegylated interferon-alpha showed a higher HBeAg seroconversion rate compared to the other nucleos(t)ide analogues in several studies. Ropeginterferon alfa-2b (P1101) is a novel mono-pegylated recombinant proline-interferon alfa-2b and only has one major positional isomer with longer duration. In the results of phase II study, P1101 showed long-acting by every other week injection dosing frequency, comparing to every week injection duration of other pegylated interferon-alfa. Recently, several biomarkers related to the efficacy of antiviral therapy have been identified. Integration of potential biomarker in this adequate and well-controlled clinical study is to determine whether P1101 could induce high HBeAg seroconversion occurrence in certain biomarker-selected populations, which identified a high efficacy population in P1101 treatment in HBeAg positive chronic hepatitis B virus infection patients.