Post-infection viral superinfection technology could treat HBV and HCV patients with unmet needs.

Abstract

Background: Viral hepatitis deaths from acute infection, cirrhosis, and liver cancer have risen from the tenth to the seventh leading cause of death worldwide between 1990 and 2013. Even in the oral direct acting antiviral (DAA) agent era there are still large numbers of patients with unmet needs. Medications approved for treatment of chronic hepatitis B virus (HBV) infection do not eradicate HBV often requiring treatment for life associated with risks of adverse reactions, drug resistance, nonadherence, and increased cost. Although DAAs increased virologic cure rates well over 90% in all hepatitis C virus (HCV) genotypes, HCV infection still cannot be cured in a small but significant minority of patients. While most of the medical issues of HCV treatment have been solved, the current costs of DAAs are prohibitive.

Results: The post-infection viral superinfection treatment (SIT) platform technology has been clinically proven to be safe and effective to resolve acute and persistent viral infections in 42 HBV and HCV patients (20 HBV, 22 HCV), and in 4 decompensated patients (2 HBV, 2 HCV). SIT employs a non-pathogenic avian double stranded RNA (dsRNA) virus, a potent activator of antiviral gene responses. Unexpectedly, SIT is active against unrelated DNA (HBV) and RNA (HCV) viruses. SIT does not require lifelong therapy, which is a major advantage considering present HBV treatments. The new viral drug candidate (R903/78) is homogeneously produced by reverse genetics in Vero cells. R903/78 has exceptional pH and temperature stability and also excellent long-term stability; therefore, it can be orally administered, stored and shipped without freezing. Since R903/78 is easy to stockpile, the post-infection SIT could also alleviate the logistic hurdles of surge capacity in vaccine production during viral pandemics.

Conclusion: To help large number of HBV and HCV patients with unmet needs, broad-spectrum antiviral drugs effective against whole classes of viruses are urgently needed. The innovative SIT technological platform will be a great additional armament to conquer viral hepatitis, which is still a major cause of death and disability worldwide.