Taiwan-based pharmaceutical company CytoPharm and Texas-based biotech Amarillo Biosciences released positive clinical findings from a dose-ranging, phase II clinical trial of patients infected with hepatitis C virus (HCV) in Taiwan.
A total of 169 patients with HCV (genotype 1b) were randomized to receive oral lozenges containing 500 or 1500 international units (IU) of natural human interferon-alpha (IFNa) or matching placebo for 24 weeks, followed by 24 weeks of untreated observation. All randomized patients were in viral remission, having just completed at least 24 weeks of treatment with injectable IFNa and Ribavirin.
High dose injectable IFNa is known to cause thrombocytopenia (a reduction in platelet count) via bone marrow suppression that can be severe. In the current study of HCV patients in viral remission, 60% of evaluable subjects started the study with a platelet count below the normal range.
When assessed at study entry, the treatment groups did not differ in mean platelet count. However, the subjects who received 500IU IFNa per day, but not 1500IU, had significantly greater (improved) mean platelet counts, compared to subjects in the placebo group, at study weeks 24, 36 and 48. The 500IU IFNa treatment group also had a significantly higher percentage of subjects whose platelets increased into the normal range, and by the end of the study 81% of the patients with a low starting platelet count given 500IU IFNa per day had normalized their platelets versus only 42% in the placebo group.
The primary aim of this study was to reduce the rate of virological relapse of HCV patients by 60%, from a predicted 50% in the placebo group to 20% with oral IFNa treatment. Based on intent-to-treat analysis, the relapse rate was similar in all three groups at the end of the study period.
However, a beneficial trend was noted in the approximately 40% of study subjects who had mild liver fibrosis (scarring) as determined by FibroIndex scores computed at baseline. In this sub-group, only 12% of HCV patients given 500IU IFNa per day experienced virological relapse by the end of the study, compared to 32% in the placebo group, a 63% reduction in relapse rate. A detailed final study report is expected to be available in the third quarter, to be followed by publication of full results in the coming months.
While requiring verification from larger, phase III studies, the practical clinical implication of these results is that half to two-thirds of all HCV patients successfully achieving viral remission after completing induction therapy would be candidates for oral IFNa to either prevent relapse or reverse thrombocytopenia induced by treatment with injectable IFNa. This represents millions of patients per year who could benefit from this inexpensive oral medication with minimal side effects.
Currently, there are no oral medications approved by the FDA for treating thrombocytopenia.