New HCV Drugs at AASLD

From NATAP:

from Jules: below are links to key data reports on the many new oral HCV drugs at various stages of development and there are numerous drugs in development from the various new classes which include protease inhibitors, polymerase inhibitors (nucleosides, nucletides, various types of NNRTIs), NS5A inhibitors, and if pegIFN must be used there is peg-lambda IFN. Of course Vertex & Merck presented phase 3 data results at AASLD but also there were many data updates from the other drugs in earlier stages of development. Response-Gulded Therapy (RGT) will be the new mantra in HCV therapy once the 1st oral drugs hit the market and this means patients & clinicians must bring in patients at time-checks early after starting therapy to see if viral load is undetectable or not; these time-point checks to decide if a patient should continue or stop therapy, and I see this concept continuing to be refined over time, we will move towards 16 week or even 12 week total therapy as we improve regimens to include 3 or 4 orals with or without peg/rbv.

In the Vertex large phase 3 ADVANCE Study of the HCV protease inhibitor telaprevir, which included over 1000 genotype 1 treatment-naïve patients presented at AASLD, study patients who received telaprevir plus Pegasys/rbv had a significantly higher SVR (Sustained Viral Response, cure): 75% vs 44% of patients who received just Pegasys/rbv. These numbers included patients who had either 24 or 48 weeks total therapy. Patients, both blacks and whites, who had undetectable viral load at the early time-checkpoints, weeks 4 and 12, about 90% achieved SVR. In the Merck SPRINT-2 phase 3 Study of boceprevir presented at AASLD, over 1000 genotype 1 treatment-naïve patients participated, patients received either boceprevir plus Pegintron/rbv or just Pegintron/rbv, with 67-71% of non-Blacks achieving a SVR (cure) vs 40% for study patients who received Pegintron/rbv, and 42-53% of Blacks achieving cure vs 23% who received only Pegintron/rbv, these results were for patients who had a total duration of therapy of 24 or 48 weeks. An undetectable viral load at the early time-check-points in this study, weeks 8 and 24, also achieved high rates of SVR, cure.

How much affect on outcome (SVR) will IL28B and the genotype 1a vs 1b have once oral therapy are added to peg/RBV remains to be seen, but certainly as you add more than 1 oral to peg/rbv their impact will diminish & eventually be minimal or disappear altogether. BMS presented the early data, the 1st data in null-responders receiving 2 orals only or 2 orals plus peg/rbv, the results from this study were highly anticipated and begin to give us important information on treatment without peg/rbv but also in treating null-responders, as all 10 null-responders had undetectable viral load after 12 weeks with all 4 drugs. After initial monotherapy ABT-450 looked very potent, perhaps a 6-log drug. The nucleoside polymerase R7128 shows good 12 week data underscoring the importance that this drug or class appears not be associated with resistance developing easily & early, and this is important. Pharmasset presented data on 2 nucleotides with potency & also the possibility of not be associated with resistance developing. The BMS NS5A is potent. Some drugs are administered once daily, some three times daily, the side effects profiles differ between the drugs, and success with therapy will require management of side effects, like anemia. The data from both Vertex & Merck show that African-Americans can have response rates as high as whites if they have early RGT results, that is if the viral load is undetectable at the early-time-points the cure or SVR rates are equally high for blacks, latinos and whites.

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