We don't know how drug resistance to HCV oral drugs will play out

New HCV Drugs, Resistance, FDA Drug Development Guidance

from Jules: We don't know how drug resistance to HCV oral drugs will play out, as you can see from this most recently presented and summarized from study data, mutations can emerge but apparently more in prior nonresponders than naives as reported in the telaprevir data immediately below. Mutations persisted for some patients who failed, but in the TMC435 study patients previously treated with monotherapy & retreated with triple (+peg/rbv) 9/10 achieved undetectable after 28 days but when these patients were retreated the mutations were not detectable so we don't know what could happen for patients who accumukate many mutations perhaps because they were left on failing therapy and have detectable mutations upon retreatment. Still, there are many classes of new HCV drugs in development including nucleosides (R7128), nucleotides in early development by Pharmasset, several types NNRTIs that appear they bind at different spots and could be used together perhaps, and NS5A inhibitors, so if HCV protease inhibitor drug resistance causes a problem we expect these other classes of HCV drugs to become available. Two protease inhibitors are expected to become available by Sept 2011, telaprevir & boceprevir, these other drugs will take longe r as they are further back in the development process, perhaps another 2 years approximately. Patients and clinicians need to make treatment decisions often based on the stage of a patient's disease, perhaps for some patients with more advanced they cannot wait much longer and may need to be treated next year while perhaps others could wait. In studies of telaprevir + peg/rbv in treatment-naives a recently released study reported 75% SVR rates, this was a bit higher than seen in phase 2 studies where 61-69% SVR was seen, but side effects are likely becoming more manageable causing less discontinuations & these patients in the 75% study were easier to treat with less advanced disease. When 2 or more oral drugs are combined with peg/rbv SVR rates of 80% or more are expected. It is expected that although African-Americans do not respond as well to peg/rbv they should respond equally well to oral HCV drugs as caucasians.