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Telaprevir PROVE3 Final Results: treatment-experienced patients
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Reported by Jules Levin
AASLD Nov 2 2009, Boston, MA
Vertex presented PROVE3 final results, a phase 2 study, in 435 HCV+ genotype 1 treatment-experienced patients who did NOT achieve an SVR, sustained viral response with prior peginterferon/ribavirin therapy. They reported results from this study at EASL in April 2009, so these are essentially the same data, but just the final results. Patients were non-responders, relapsers and breakthroughs, definitions of these terms are below. In phase 3 null-responders are being studies. RESULTS: 39% of Prior non-responders (26/66) achieved SVR in the T12/PR24 group: telaprevir+peg/rbv for 12 wks, then only peg/rbv for another 12 wks); 38% achieved SVR (24/64) in the T24/PR48 group: telaprevir+peg/rbv for 24 wks, then only peg/rbv for another 24 wks). Prior relapsers did well: 76% with longer treatment regimen (24 wks TLV/48 wks peg/rbv) achieved SVR, 69% with shorter regimen (12 wks TLV/24 wks peg/rbv). Of note in a Press Release yesterday Vertex announced seeing a much higher rate of SVR in null-responders from a different study being presented here. Phase 3 studies are ongoing. Expected approval of telaprevir is in 2011. The Relapse rates were higher in the patient group getting telaprevir for only 12 weeks plus peg/rbv for a tota of 24 weeks, compared to the patient group receiving telaprevir for 24 weeks plus peg/rbv for total of 48 weeks (29% vs 4-13%). As well, the viral breakthrough rates were higher in prior breakthroughs taking the shorter regimen here (14% vs 0%), see picture of graph below). Although among prior non-responders the viral breakthrough rates were similar 20% vs 22% and the same for prior relapsers but only 2% vs 0%. Patients without cirrhosis tended to do better suggesting treating earlier might be better for this and aditinal reasons, except among non-reponders SVR rate was 53% for cirrhotivs & 51% for non-cirrhotics. 100% of SVR patients maintained undetectable HCVRNA 48 weeks after having completed treatment. Most common adverse events in patients receiving telaprevir were as expected: rash (all types), pruritis (itching), diarrhea, insomnia, anemia. Discontinuation from study drugs was 5% due to rash among the 40-60% reporting any rash on telaprevir-based regimens, anemia: only 2% on telaprevir-based regimen compared to 1% on peg/rbv arm, 3-5% due to GI disorders on telaprevir-based regimens compared to 1% on only peg/rbv.
STUDY DESIGN
4 arms;
T12/PR24 - 12 weeks of telaprevir + peg/RBV, then 12 weeks of only peg/rbv
T24/PR48 - 24 weeks telaprevir+peg/rbv, then 24 weeks of peg/rbv
T24/24 - 24 weeks telaprevir+pegIFN only, no RBV
PR48 (control group) ONLY pegIFN+RBV + telaprevir placebo for 24 weeks, then placebo eliminated and only peg/rbv for the next 24 weeks
Overall: patients who had undetectable HCV RNA at the last dose of treatment
Completed regimen: patients who completed assigned treatment & had undetectable HCV RNA after the last dose of treatment.
reported in 20% or more of patients regardless of severity in any treatment arm.
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