Aa
results of 12-Week Interferon-Free Regimen + riba
http://www.gastroendonews.com/ViewArticle.aspx?d=Hepatology+in+Focus&d_id=481&i=August+2012&i_id=871&a_id=21419
12-Week Interferon-Free Regimen of ABT-450/R + ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders (Poordad F et al)
In this multicenter trial, HCV genotype 1 patients (mostly genotype 1a) were randomized to one of three groups: 1) 19 treatment-naive patients received 250 mg of ABT-450, an NS3 HCV PI, boosted with ritonavir 100 mg daily, 400 mg of ABT-333, a non-nucleoside HCV polymerase inhibitor, and RBV 1,000 to 1,200 mg; 2) 14 treatment-naive patients received the same drug regimen with a lower ritonavir-boosted ABT-450 dose of 150 mg daily; 3) 17 HCV patients who were prior non-responders received the same low ABT-450 dose regimen as the second group. Treatment duration in all arms was 12 weeks. Ten patients in the high-dose ABT-450 group, five in the low-dose group and none of the non-responders had the interleukin-28 B (IL28B) CC genotype. There were no other significant differences between groups.
Data analysis revealed all patients in the high-dose group achieved a rapid virologic response, defined as HCV RNA less than 25 IU/mL at week 4 compared with 92.9% of low-dose treatment-naive patients and 88.2% of low-dose treatment-experienced prior non-responders. Nearly 95% and 93% of patients in the high- and low-dose groups, respectively, achieved SVR at four and 12 weeks, while SVR at weeks 4 and 12 was achieved in 47% of low-dose ABT-450 prior non-responders. Six prior non-responders experienced viral breakthrough during treatment, and three experienced relapse following treatment.
Among treatment-naive patients, IL28B genotype did not affect the likelihood of virologic response.
Common AEs included fatigue (42%), nausea (22%) and headache (20%), with no significant differences among the three groups. One patient experienced hyperbilirubinemia.
Dr. Jacobson: The very high SVR rates reported in this study, with a mere 12 weeks of therapy, were deeply gratifying and perhaps somewhat surprising in light of the fact that neither of the DAAs have a high barrier to resistance. The regimen’s success may testify to the utility of RBV in preventing resistance, or possibly, as some have speculated, to high intrahepatic concentrations of ritonavir-boosted ABT-450, permitting suppression of low-level resistant variants. The lower SVR rates in null responders, associated with substantial relapse rates, reflect an important emerging and unanticipated theme—the importance of host pathways, reflected by IFN responsiveness, in mediating viral eradication with IFN-free regimens. Whether this can be overcome with “optimized” antiviral regimens remains to be seen. This regimen has great promise and its components are being further evaluated with the addition of an NS5A inhibitor to the armamentarium.
12-Week Interferon-Free Regimen of ABT-450/R + ABT-333 + Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders (Poordad F et al)
In this multicenter trial, HCV genotype 1 patients (mostly genotype 1a) were randomized to one of three groups: 1) 19 treatment-naive patients received 250 mg of ABT-450, an NS3 HCV PI, boosted with ritonavir 100 mg daily, 400 mg of ABT-333, a non-nucleoside HCV polymerase inhibitor, and RBV 1,000 to 1,200 mg; 2) 14 treatment-naive patients received the same drug regimen with a lower ritonavir-boosted ABT-450 dose of 150 mg daily; 3) 17 HCV patients who were prior non-responders received the same low ABT-450 dose regimen as the second group. Treatment duration in all arms was 12 weeks. Ten patients in the high-dose ABT-450 group, five in the low-dose group and none of the non-responders had the interleukin-28 B (IL28B) CC genotype. There were no other significant differences between groups.
Data analysis revealed all patients in the high-dose group achieved a rapid virologic response, defined as HCV RNA less than 25 IU/mL at week 4 compared with 92.9% of low-dose treatment-naive patients and 88.2% of low-dose treatment-experienced prior non-responders. Nearly 95% and 93% of patients in the high- and low-dose groups, respectively, achieved SVR at four and 12 weeks, while SVR at weeks 4 and 12 was achieved in 47% of low-dose ABT-450 prior non-responders. Six prior non-responders experienced viral breakthrough during treatment, and three experienced relapse following treatment.
Among treatment-naive patients, IL28B genotype did not affect the likelihood of virologic response.
Common AEs included fatigue (42%), nausea (22%) and headache (20%), with no significant differences among the three groups. One patient experienced hyperbilirubinemia.
Dr. Jacobson: The very high SVR rates reported in this study, with a mere 12 weeks of therapy, were deeply gratifying and perhaps somewhat surprising in light of the fact that neither of the DAAs have a high barrier to resistance. The regimen’s success may testify to the utility of RBV in preventing resistance, or possibly, as some have speculated, to high intrahepatic concentrations of ritonavir-boosted ABT-450, permitting suppression of low-level resistant variants. The lower SVR rates in null responders, associated with substantial relapse rates, reflect an important emerging and unanticipated theme—the importance of host pathways, reflected by IFN responsiveness, in mediating viral eradication with IFN-free regimens. Whether this can be overcome with “optimized” antiviral regimens remains to be seen. This regimen has great promise and its components are being further evaluated with the addition of an NS5A inhibitor to the armamentarium.
Hi Cheese! On the face of it you would appear to be right. I can't help wondering though if the non-responders would have got a better result from a longer duration with this combo or not?
I'm guessing that using DAA's with a high barrier to resistance might be the key for success with the non-responders, as well as a longer duration. The standout is ofcourse 7977.
Good to hear from you,
dointime
I'm guessing that using DAA's with a high barrier to resistance might be the key for success with the non-responders, as well as a longer duration. The standout is ofcourse 7977.
Good to hear from you,
dointime
It seems very clear by now.
Non-responders and nulls will need more than 12 weeks all oral.
Let's stop dicking around and causing heartache with 12 weeks for nulls/non-responders!
Non-responders and nulls will need more than 12 weeks all oral.
Let's stop dicking around and causing heartache with 12 weeks for nulls/non-responders!
"The lower SVR rates in null responders, associated with substantial relapse rates, reflect an important emerging and unanticipated theme—the importance of host pathways, reflected by IFN responsiveness, in mediating viral eradication with IFN-free regimens."
Oh dear. Very bad news for non-responders if this proves to be true. Just when we thought that the all-orals might get us over this particular roadblock. Early days yet though. We watch and wait.
dointime
Oh dear. Very bad news for non-responders if this proves to be true. Just when we thought that the all-orals might get us over this particular roadblock. Early days yet though. We watch and wait.
dointime
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