UK company MicroScience has completed a Phase I study of a new therapeutic vaccine for patients carrying the hepatitis B virus, raising the hope of a new approach to tackling this life-threatening infection.
The vaccine, based on Microscience's spi-VEC technology, can be given orally and rather than protecting against HBV infection is specifically designed in the first instance to promote clearance of the virus in patients who are carrying the infection.
There are some 350 million carriers of chronic hepatitis B carriers worldwide, accounting for one million deaths per year and current treatments offer only limited efficacy.
At present, the standard treatments for chronic hepatitis B are interferon alpha and GlaxoSmithKline's nucleoside analogue Epivir (lamivudine), which was introduced in 1998.
More recently, Gilead Sciences has been granted approval for a nucleotide-based drug, Hepsera (adefovir dipivoxil). Gilead has a follow-up drug for HBV in trials - called emtricitabine - while other hopefuls include Metabasis with remofovir mesylate and Idenix/Novartis with telbivudine.
But these treatment approaches do not work to clear the virus in all cases, and in the case of the interferons require careful patient monitoring because of the risk of serious side effects. Microscience hopes that its vaccine could be added to the HBV armamentarium to boost viral clearance rates.
Most cases of chronic HBV are found in Asia, with around nine million individuals with the infection in Europe. Analysts have predicted that an effective drug-based treatment for the disease could achieve sales of $500 million or more, depending on take-up rates in Asia.
While still only preliminary, Microscience's Phase I clinical study met its primary objectives and successfully demonstrated safety and immunogenicity, supporting the vaccine's continued development as a therapeutic for chronic HBV carriers.
The open-label, dose-escalating study was performed in 30 healthy adult volunteers to evaluate the safety and immunogenicity of a candidate oral immunotherapy given on two occasions, 56 days apart. The primary aim of the study was to assess safety and to determine the cellular immune responses against hepatitis B core antigen (HBcAg).
It is known that a cellular immune response is critical for an immunotherapy to be effective against this life-threatening infection., and the immunological data from the trial have demonstrated that all subjects mounted a T-cell proliferative response to both the HBcAg and to groups of peptides representing the whole sequence of HbcAg. This suggests that the antigen had been successfully delivered to the immune system in all subjects.
In addition, 95 per cent of responders in the high dose group elicited a Th1-biased response characterised by the secretion of gamma interferon and the absence of IL-5 secretion by stimulated T-cells. Th1 responses are known to play an important role in the promotion of viral clearance in chronic hepatitis B.
Rod Richards, Microscience's CEO, commented: "These results are very exciting as they demonstrate that the spi-VEC-based vaccine stimulates the appropriate type of immune response required to promote clearance of the hepatitis B virus in chronic carriers."
He said the company is now planning a Phase II programme in subjects chronically infected with the virus.
Microscience has also shown proof of principle with an spi-VEC-based vaccine against enterotoxigenic Escherichia coli (ETEC) or travellers' diarrhoea.