Biotron (ASX:BIT) has announced interim data from a Phase 2, three-month dosing study of its lead drug BIT225 in patients with Hepatitis C virus (HCV) genotypes 1 or 3 (G1 and G3).
In the BIT225-008 trial, a double-blind, placebo controlled study undertaken at several sites in Thailand, 60 patients infected with HCV G1 or G3 were treated for 12 weeks with either BIT225 or placebo, in combination with pegylated interferon alfa-2b and ribavirin (IFN/RBV).
At the conclusion of this 12 week period, HCV G3 patients continued to receive IFN/RBV for an additional 12 weeks. HCV G1 patients continued to receive IFN/RBV for an additional 36 weeks.
The HCV G3 cohort has now reached week 36 of the study. All G3 patients have been off all drugs for 12 weeks and hence at the SVR12 time point. The last patients in the HCV G1 cohort continue with IFN/RBV treatment until late 1Q16 and will be reported on at that time.
The primary objectives of the trial were to gather safety and tolerability data that will be key in determining dosing regimens and levels in future studies with BIT225. Secondary objectives of assessment were to study the pharmacokinetics and antiviral efficacy.
The delivery of BIT225 was found to be greater on a mg/kg basis than in the previous single dose bioequivalence trial, leading to higher than expected accumulation over repeated doses.
This data provides Biotron with important information on the dose and dosing frequency selection for future trials, indicating that a lower dose and less dose frequency may be achievable without compromising the efficacy of BIT225.
There is potential for once a day dosing which would be a major economic and efficacy advantage in many of the target populations, the company said.
The endpoint of HCV treatment is a sustained virologic response (‘SVR’). Sustained virologic response at week 12 (‘SVR12’) is defined as an undetectable HCV RNA level 12 weeks after completion of all treatment. It is considered to be a prediction of permanent clearance of the virus.
According to Biotron, both treatment groups, BIT225/IFN/SBV and placebo/IFN/RBV, achieved a very high rate of clearance of virus.
"Only one patient in each group did not achieve SVR12. The reported historical average of HCV G3 patients achieving SVR12 treated with IFN/RBV in Thailand is 68%. The BIT225/IFN/RBV cohort had 88% (7/8) SVR12 compared to the placebo/IFN/RBV treatment group's 90% (9/10) SVR12 in a per protocol evaluation. There was no statistically significant difference between the treatment arms."
“The higher than expected rate of 90% SVR12 in the IFN/RBV group means that no significant improvement in SVR12 can be shown with the addition of BIT225 in the HCV G3 population in this study," said Biotron Managing Director, Dr Michelle Miller.
"It is unfortunate that six patients were unnecessarily lost to the study under the stopping rule. However, whilst no significant improvement in SVR12 can be shown with the addition of BIT225 in the HCV G3 population in this study, the 88% SVR12 rate is significantly better than the 68% historical reported average.”
“This trial has generated positive key safety and pharmacokinetic data, which will be central to determining dose and frequency of dosing in future trials with BIT225,” added Dr Miller.
The company said data from the study, in combination with data from the other seven clinical trials undertaken with BIT225 in healthy volunteers as well as in HIV, HCV and HIV/HCV co-infected populations, is undergoing detailed analyses with expert groups in the US.
"The results of these analyses, along with the clinical study reports, extensive non-clinical toxicology reports and a detailed report on Chemistry, Manufacturing and Control (‘CMC’) of the compound will form the core of a comprehensive data package on BIT225," it sadi.
Biotron said it expects to submit the data package to the US FDA in the form of an IND application in late 2015.
"Importantly, the data package will also be central to discussions with potential commercial partners for the next stage of clinical development of BIT225," it said.