Aa
Telaprevir Abstracts AASLD 2007
Telaprevir resistance mutations in patients with hepatitis C who relapsed after sequential therapy with telaprevir, peg-interferon alfa 2a and ribavirin
N. Forestier1, 2; S. Susser2; M. W. Welker2; C. J. Weegink3; H. W. Reesink3; S. Zeuzem1, 2; C. Sarrazin1, 2
1. Internal Medicine I, J. W. Goethe University Hospital, Frankfurt, Germany.
2. Internal Medicine II, Saarland University Hospital, Homburg, Germany.
3. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands.
Introduction: Telaprevir (TVR) is a highly selective inhibitor of the hepatitis C virus (HCV) NS3/4A protease with highly effective blocking of HCV replication in patients with hepatitis C. Mutations have been identified in the NS3 protease gene at positions 36, 54, 155 and 156 conferring resistance to TVR in vitro and in vivo. For single resistance mutations an inverse correlation of resistance level and viral fitness has been described while combined mutations (i.e. V36/R155) display relative high resistance with compensatory effects on replication efficiency. Little is known about persistence of TVR resistance mutations in patients treated sequentially with TVR, peg-interferon and ribavirin (RBV). Methods: Fifteen patients received either TVR monotherapy or TVR peg-interferon alfa 2a combination therapy for 2 weeks followed by peginterferon alfa 2a plus RBV standard combination therapy for 24 or 48 weeks. In the present study, we performed amplification and clonal sequencing (approx. 50 clones per patient and time point) of the HCV NS3 protease gene in 5 patients who relapsed so far. All 5 patients were tested HCV RNA negative during therapy but relapse with increasing HCV RNA concentration was observed after the end of standard combination treatment for 24 or 48 weeks. Results: While in 2 patients no mutations conferring resistance to TVR were detected during different time points after relapse, in 3 patients known TVR resistance mutations within the NS3 protease gene were detected. Patient 1 with initial TVR monotherapy, 48 weeks of standard therapy, and relapse at week 4 after treatment discontinuation (433.000 IU/ml) showed mutations at positions V36 (100% of clones) and R155 (100% of clones). In patient 2 with initial TVR monotherapy, 24 weeks of standard treatment and relapse at week 4 (viral load pending) only single isolates with resistance mutations were observed at position V36 (2%) and A156 (2%). Finally, patient 3 received initially combination therapy followed by 48 weeks of standard treatment. In this patient relapse was detected at follow up week 8 (1.400 IU/ml) and resistance mutations were detected at position V36 (84% of clones) only. In both patients who received TVR monotherapy mutations at positions V36, T54, R155 and A156 were observed during the initial 2 weeks of treatment. Conclusion: In patients treated with TVR with and without peginterferon alfa 2a for 2 weeks followed by standard therapy with peginterferon and RBV for 24 or 48 weeks mutations conferring resistance to TVR can be detected after relapse. The significance of TVR resistance mutations for the probability of relapse has to be investigated in future studies.
(MORE TO FOLLOW)
N. Forestier1, 2; S. Susser2; M. W. Welker2; C. J. Weegink3; H. W. Reesink3; S. Zeuzem1, 2; C. Sarrazin1, 2
1. Internal Medicine I, J. W. Goethe University Hospital, Frankfurt, Germany.
2. Internal Medicine II, Saarland University Hospital, Homburg, Germany.
3. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands.
Introduction: Telaprevir (TVR) is a highly selective inhibitor of the hepatitis C virus (HCV) NS3/4A protease with highly effective blocking of HCV replication in patients with hepatitis C. Mutations have been identified in the NS3 protease gene at positions 36, 54, 155 and 156 conferring resistance to TVR in vitro and in vivo. For single resistance mutations an inverse correlation of resistance level and viral fitness has been described while combined mutations (i.e. V36/R155) display relative high resistance with compensatory effects on replication efficiency. Little is known about persistence of TVR resistance mutations in patients treated sequentially with TVR, peg-interferon and ribavirin (RBV). Methods: Fifteen patients received either TVR monotherapy or TVR peg-interferon alfa 2a combination therapy for 2 weeks followed by peginterferon alfa 2a plus RBV standard combination therapy for 24 or 48 weeks. In the present study, we performed amplification and clonal sequencing (approx. 50 clones per patient and time point) of the HCV NS3 protease gene in 5 patients who relapsed so far. All 5 patients were tested HCV RNA negative during therapy but relapse with increasing HCV RNA concentration was observed after the end of standard combination treatment for 24 or 48 weeks. Results: While in 2 patients no mutations conferring resistance to TVR were detected during different time points after relapse, in 3 patients known TVR resistance mutations within the NS3 protease gene were detected. Patient 1 with initial TVR monotherapy, 48 weeks of standard therapy, and relapse at week 4 after treatment discontinuation (433.000 IU/ml) showed mutations at positions V36 (100% of clones) and R155 (100% of clones). In patient 2 with initial TVR monotherapy, 24 weeks of standard treatment and relapse at week 4 (viral load pending) only single isolates with resistance mutations were observed at position V36 (2%) and A156 (2%). Finally, patient 3 received initially combination therapy followed by 48 weeks of standard treatment. In this patient relapse was detected at follow up week 8 (1.400 IU/ml) and resistance mutations were detected at position V36 (84% of clones) only. In both patients who received TVR monotherapy mutations at positions V36, T54, R155 and A156 were observed during the initial 2 weeks of treatment. Conclusion: In patients treated with TVR with and without peginterferon alfa 2a for 2 weeks followed by standard therapy with peginterferon and RBV for 24 or 48 weeks mutations conferring resistance to TVR can be detected after relapse. The significance of TVR resistance mutations for the probability of relapse has to be investigated in future studies.
(MORE TO FOLLOW)
thanks for all the posts. Lots of reading here.
jasper
jasper
Busy posting and haven't read anything yet, but I will get around to it. That said, what you say doesn't surprise me as RVR has seemingly been ruling the SVR roost for some time now.
thanks so much for posting these data.
I have too much brain fog to trust my conclusions, but I did conclude from two abstracts, that the percentage of people that reach undetectable by week 4 is the same percentage that reaches SVR.
Did you conclude that as well or am I suffering too much from brain fatigue to process all the data?
Thanks for posting - Eric
I have too much brain fog to trust my conclusions, but I did conclude from two abstracts, that the percentage of people that reach undetectable by week 4 is the same percentage that reaches SVR.
Did you conclude that as well or am I suffering too much from brain fatigue to process all the data?
Thanks for posting - Eric
PROVE2: Phase II Study of VX950 (TELAPREVIR) in Combination with Peginterferon ALFA2A With or Without Ribavirin in Subjects With Chronic Hepatitis C, First Interim Analysis
S. Zeuzem9; C. Hezode1; P. Ferenci2; G. M. Dusheiko3; S. Pol4; T. Goeser5; J. Bronowicki6; S. Gharakhanian7; D. Devonish7; R. Kauffman7; J. Alam7; J. Pawlotsky8
1. AP-HP Hepatogastroenterology Srrvices, Henri Mondor Hospital, Creteil, France.
2. Internal Medicine III, Medical University, Vienna, Austria.
3. Center for Hepatology, Royal Free Hospital, London, United Kingdom.
4. AP-HP Liver Unit, Necker-Cochin Hospitals, Paris, France.
5. Gastroenterology & Hepatology, University of Cologne, Cologne, Germany.
6. CHU, Nancy University Hospital Center, Nancy, France.
7. Medicinal Development Group, Vertex Pharmaceuticals, Inc, Cambridge, MA, USA.
8. AP-HP Dept of Bacterology & Virology, Henri Mondor Hospital, Creteil, France.
9. Internal Medicine Clinic II, Saarland University Hospital, Homburg/Saar, Germany.
Background:
PROVE2, study VX05-950-104EU is a randomized, placebo-controlled phase II study of telaprevir (TVR), in combination with pegylated interferon alfa2a (Peg-IFN) and ribavirin (RBV), in treatment naïve subjects with genotype 1 chronic hepatitis C infection. Results of a planned interim, on-treatment, safety and efficacy analysis (IA) are reported.
Methods:
A total of 332 subjects were randomized into four groups. Group A received standard of care Peg-IFN 180 mcg/weekly + RBV 1000-1200 mg, weight-based and TVR-placebo for 48 weeks. Group B TVR 750 mg q8h together with Peg-IFN+RBV for 12 weeks, followed by Peg-IFN and RBV for a further 12 weeks. Group C, TVR 750 q8h with Peg-IFN + RBV for 12 weeks. Group D, TVR + Peg-IFN for 12 wks. The Roche Taqman assay was used to quantify plasma HCV RNA (LOD 10 IU/mL). This first IA was performed when at least 90% of subjects completed the week 12 visit.
Results:
The median age was 45 years (18-65), median weight 70.9 kg (45-115), 58.7% were male, 94.1% Caucasian, 7.5 % had stage F3 fibrosis, 34.1% were infected with genotype 1a, and 54.1% with 1b. The median baseline HCV RNA was 6.4 Log10IU/ml (3.3-7.7). Overall, discontinuation occurred in 6.4% of Group A, 17.1% of Groups B+C and 10.5% of Group D subjects prior to week 12. Discontinuations for AEs, occurred in 2.6% of Group A, 12.5% of Groups B+C and 7.9% of Group D subjects. Pruritis, rash, asthenia, nausea, and anemia were the most common AEs associated with TVR; anemia and nausea were less frequent in Group D. The table summarizes ITT viral responses.
Conclusion:
TVR (Telaprevir, VX950)+Peg-IFN+RBV produces a significantly greater, on-treatment, anti-viral response at weeks 4 and 12 compared to Peg-IFN+RBV in naïve subjects with genotype 1 HCV. Dosing without RBV reduced the on-treatment anti-viral response; further follow-up will evaluate effects on SVR and relapse rates. Consistent with prior studies, the adverse event profile showed that skin events, nausea and anemia are the most important AE’s associated with TVR. Further results will confirm the optimal treatment duration and dosage regimen for Phase 3.
HCV RNA Un-detectable Group A (%)
(n=77)
Groups B+C (%)
(n=152)
Group D (%)
(n=76)
Week 4 14.3 74.3* 52.6*
Week 12 42.9 78.9* 63.2+
*p<0.001 compared to Group A; +p=0.015 compared to group A
S. Zeuzem9; C. Hezode1; P. Ferenci2; G. M. Dusheiko3; S. Pol4; T. Goeser5; J. Bronowicki6; S. Gharakhanian7; D. Devonish7; R. Kauffman7; J. Alam7; J. Pawlotsky8
1. AP-HP Hepatogastroenterology Srrvices, Henri Mondor Hospital, Creteil, France.
2. Internal Medicine III, Medical University, Vienna, Austria.
3. Center for Hepatology, Royal Free Hospital, London, United Kingdom.
4. AP-HP Liver Unit, Necker-Cochin Hospitals, Paris, France.
5. Gastroenterology & Hepatology, University of Cologne, Cologne, Germany.
6. CHU, Nancy University Hospital Center, Nancy, France.
7. Medicinal Development Group, Vertex Pharmaceuticals, Inc, Cambridge, MA, USA.
8. AP-HP Dept of Bacterology & Virology, Henri Mondor Hospital, Creteil, France.
9. Internal Medicine Clinic II, Saarland University Hospital, Homburg/Saar, Germany.
Background:
PROVE2, study VX05-950-104EU is a randomized, placebo-controlled phase II study of telaprevir (TVR), in combination with pegylated interferon alfa2a (Peg-IFN) and ribavirin (RBV), in treatment naïve subjects with genotype 1 chronic hepatitis C infection. Results of a planned interim, on-treatment, safety and efficacy analysis (IA) are reported.
Methods:
A total of 332 subjects were randomized into four groups. Group A received standard of care Peg-IFN 180 mcg/weekly + RBV 1000-1200 mg, weight-based and TVR-placebo for 48 weeks. Group B TVR 750 mg q8h together with Peg-IFN+RBV for 12 weeks, followed by Peg-IFN and RBV for a further 12 weeks. Group C, TVR 750 q8h with Peg-IFN + RBV for 12 weeks. Group D, TVR + Peg-IFN for 12 wks. The Roche Taqman assay was used to quantify plasma HCV RNA (LOD 10 IU/mL). This first IA was performed when at least 90% of subjects completed the week 12 visit.
Results:
The median age was 45 years (18-65), median weight 70.9 kg (45-115), 58.7% were male, 94.1% Caucasian, 7.5 % had stage F3 fibrosis, 34.1% were infected with genotype 1a, and 54.1% with 1b. The median baseline HCV RNA was 6.4 Log10IU/ml (3.3-7.7). Overall, discontinuation occurred in 6.4% of Group A, 17.1% of Groups B+C and 10.5% of Group D subjects prior to week 12. Discontinuations for AEs, occurred in 2.6% of Group A, 12.5% of Groups B+C and 7.9% of Group D subjects. Pruritis, rash, asthenia, nausea, and anemia were the most common AEs associated with TVR; anemia and nausea were less frequent in Group D. The table summarizes ITT viral responses.
Conclusion:
TVR (Telaprevir, VX950)+Peg-IFN+RBV produces a significantly greater, on-treatment, anti-viral response at weeks 4 and 12 compared to Peg-IFN+RBV in naïve subjects with genotype 1 HCV. Dosing without RBV reduced the on-treatment anti-viral response; further follow-up will evaluate effects on SVR and relapse rates. Consistent with prior studies, the adverse event profile showed that skin events, nausea and anemia are the most important AE’s associated with TVR. Further results will confirm the optimal treatment duration and dosage regimen for Phase 3.
HCV RNA Un-detectable Group A (%)
(n=77)
Groups B+C (%)
(n=152)
Group D (%)
(n=76)
Week 4 14.3 74.3* 52.6*
Week 12 42.9 78.9* 63.2+
*p<0.001 compared to Group A; +p=0.015 compared to group A
Evaluation of Viral Variants During a Phase 2 Study (PROVE2) of Telaprevir with Peginterferon alfa-2A and Ribavirin in Treatment-naïve HCV Genotype 1-Infected Patients
J. Pawlotsky5; T. Kieffer1; Y. Zhou1; E. Zhang1; M. Marcial1; R. Byrn1; T. Pfeiffer1; J. Miller1; A. Tigges1; D. Bartels1; A. Kwong1; P. Ferenci2; G. Dusheiko3; S. Zeuzem4
1. Infectious Diseases, Vertex Pharmaceuticals Incorporated, Cambridge, MA, USA.
2. Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
3. Centre for Hepatology, Royal Free Hospital, London, United Kingdom.
4. Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany.
5. Department of Virology, Henri Mondor Hospital, University of Paris XII, Créteil, France.
Background: The VX05-950-104EU study (PROVE2) is a Phase 2 study of an HCV protease inhibitor, telaprevir (VX-950, TVR) 750 mg q8h, in combination with Peg-IFN-alfa-2a (P) 180 µg/week and ribavirin (R) 1000-1200 mg/day in treatment naive subjects with genotype 1 hepatitis C. Subjects were randomized into 4 groups that received: 1) TVR/P/R for 12 weeks, 2) TVR/P for 12 weeks, 3) TVR/P/R for 12 weeks followed by 12 weeks of P/R, and 4) P/R for 48 weeks (control group). Viral breakthrough (increase of > 1-log above HCV RNA nadir or increase to > 100 IU/mL in previously undetectable patients) was observed in some subjects during the first 12 weeks of therapy. Viral sequencing was used to evaluate the contribution of TVR resistance to antiviral response.
Methods: Plasma samples for viral sequencing were taken at baseline and at each HCV RNA assessment. The NS3-4A RNA region was amplified by nested RT-PCR and sequenced in samples with HCV RNA > 1,000 IU/mL. Prospectively defined criteria for identifying potential resistance mutations were applied using a Poisson distribution.
Results: HCV RNA was undetectable (LOD 10 IU/mL) at Week 4 in 14% of subjects in the P/R group, 74% in the TVR/P/R groups (p<0.001), and 53% in the TVR/P group (p<0.001); and at Week 12 in 43% of subjects in the P/R group, 79% in the TVR/P/R groups (p<0.001), and 63% in the TVR/P group (p<0.015). During the first 12 weeks on treatment, 6 of 152 subjects (4%) in the TVR/P/R groups, 19 of 76 subjects in the TVR/P group (25%), and 1 of 77 subjects (1%) in the P/R group had viral breakthrough. The breakthroughs were associated with wild-type virus in the P/R group and previously identified TVR-resistant variants in the TVR groups (TVR/P/R: genotype 1a, n=4: mainly V36M and R155K; genotype 1b, n=2: mainly A156T; TVR/P: genotype 1a, n=12: mainly V36M and R155K; genotype 1b, n=7: mainly V36A, T54A, R155K, and A156S/T).
Conclusions: In this interim analysis, TVR/P/R produced a significantly greater antiviral response at Weeks 4 and 12 compared to TVR/P and P/R in treatment naïve subjects with genotype 1 HCV. In the TVR groups, viral breakthroughs were associated with the selection of known TVR-resistant variants. The breakthrough rate in the TVR/P group was higher than in the TVR/P/R groups, suggesting that suboptimal inhibition of viral replication provides a greater probability for selection of TVR-resistant variants. Some subjects with viral breakthrough on TVR had a subsequent decline in HCV RNA during treatment with P/R, indicating that emergence of TVR-resistance does not preclude response to P/R.
*on behalf of the PROVE2 Study Team
J. Pawlotsky5; T. Kieffer1; Y. Zhou1; E. Zhang1; M. Marcial1; R. Byrn1; T. Pfeiffer1; J. Miller1; A. Tigges1; D. Bartels1; A. Kwong1; P. Ferenci2; G. Dusheiko3; S. Zeuzem4
1. Infectious Diseases, Vertex Pharmaceuticals Incorporated, Cambridge, MA, USA.
2. Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
3. Centre for Hepatology, Royal Free Hospital, London, United Kingdom.
4. Department of Medicine I, J.W. Goethe University Hospital, Frankfurt, Germany.
5. Department of Virology, Henri Mondor Hospital, University of Paris XII, Créteil, France.
Background: The VX05-950-104EU study (PROVE2) is a Phase 2 study of an HCV protease inhibitor, telaprevir (VX-950, TVR) 750 mg q8h, in combination with Peg-IFN-alfa-2a (P) 180 µg/week and ribavirin (R) 1000-1200 mg/day in treatment naive subjects with genotype 1 hepatitis C. Subjects were randomized into 4 groups that received: 1) TVR/P/R for 12 weeks, 2) TVR/P for 12 weeks, 3) TVR/P/R for 12 weeks followed by 12 weeks of P/R, and 4) P/R for 48 weeks (control group). Viral breakthrough (increase of > 1-log above HCV RNA nadir or increase to > 100 IU/mL in previously undetectable patients) was observed in some subjects during the first 12 weeks of therapy. Viral sequencing was used to evaluate the contribution of TVR resistance to antiviral response.
Methods: Plasma samples for viral sequencing were taken at baseline and at each HCV RNA assessment. The NS3-4A RNA region was amplified by nested RT-PCR and sequenced in samples with HCV RNA > 1,000 IU/mL. Prospectively defined criteria for identifying potential resistance mutations were applied using a Poisson distribution.
Results: HCV RNA was undetectable (LOD 10 IU/mL) at Week 4 in 14% of subjects in the P/R group, 74% in the TVR/P/R groups (p<0.001), and 53% in the TVR/P group (p<0.001); and at Week 12 in 43% of subjects in the P/R group, 79% in the TVR/P/R groups (p<0.001), and 63% in the TVR/P group (p<0.015). During the first 12 weeks on treatment, 6 of 152 subjects (4%) in the TVR/P/R groups, 19 of 76 subjects in the TVR/P group (25%), and 1 of 77 subjects (1%) in the P/R group had viral breakthrough. The breakthroughs were associated with wild-type virus in the P/R group and previously identified TVR-resistant variants in the TVR groups (TVR/P/R: genotype 1a, n=4: mainly V36M and R155K; genotype 1b, n=2: mainly A156T; TVR/P: genotype 1a, n=12: mainly V36M and R155K; genotype 1b, n=7: mainly V36A, T54A, R155K, and A156S/T).
Conclusions: In this interim analysis, TVR/P/R produced a significantly greater antiviral response at Weeks 4 and 12 compared to TVR/P and P/R in treatment naïve subjects with genotype 1 HCV. In the TVR groups, viral breakthroughs were associated with the selection of known TVR-resistant variants. The breakthrough rate in the TVR/P group was higher than in the TVR/P/R groups, suggesting that suboptimal inhibition of viral replication provides a greater probability for selection of TVR-resistant variants. Some subjects with viral breakthrough on TVR had a subsequent decline in HCV RNA during treatment with P/R, indicating that emergence of TVR-resistance does not preclude response to P/R.
*on behalf of the PROVE2 Study Team
Final Results of Patients Treated with Peg-Interferon-Alfa-2a (Peg-IFN) and Ribavirin (RBV) Follow-on Therapy After 28-Day Treatment with the Hepatitis C Protease Inhibitor Telaprevir (VX-950), Peg-IFN and RBV
M. Rodriguez-Torres1; E. J. Lawitz2; J. G. McHutchison3
1. Fundacion de Investigacion de Diego, Santurce, PR, USA.
2. Alamo Medical Research, San Antonio, TX, USA.
3. Duke Clinical Research Institute & Division of Gastroenterology, Duke University, Durham, NC, USA.
Purpose: Telaprevir (TVR, VX-950) is an orally administered, highly selective peptidomimetic inhibitor of the Hepatitis C virus (HCV) NS3-4A protease. The VX05-950-102 study was designed to assess the safety of telaprevir when given in combination with Peginterferon alfa-2a (Peg-IFN) and ribavirin (RBV) and to evaluate the antiviral response during 28 days of dosing. After completion of the 28-day study, all subjects received off-study therapy with Peg-IFN/RBV under the clinical care of their physicians. Here we report the outcome of treatment after this post-study therapy.
Methods: This study included 12 treatment-naïve, mostly Latino (10/12),patients infected with genotype 1. All subjects received TVR (750 mg q8h), Peg-IFN alfa-2a (180 µg weekly), and RBV (1000 or 1200 mg daily). At the completion of the 28 days, patients began off-study follow-on therapy with Peg-IFN alfa -2a/RBV.
Results: TVR/Peg-IFN/RBV was well tolerated in the 28-day study, with no serious adverse events. The adverse event profile was consistent with the profile commonly seen with Peg-IFN/RBV therapy. All subjects demonstrated a response to the study drug regimen, with 2 subjects reaching undetectable (< 10 IU/mL, Roche Taqman® Assay) levels of plasma HCV RNA within 8 days of the start of dosing, and all subjects had undetectable HCV RNA at the end of the 28-day study dosing period. At 12 weeks of follow-on therapy after completing the 28-day study dosing, 11 subjects had undetectable HCV RNA. All subjects continued on Peg-IFN/RBV therapy, and were followed for response in accordance with standard practice. Seven patients received a total of 48 weeks of treatment and achieved SVR. One patient received Peg-IFN/RBV for only 18 weeks (total treatment 22 weeks) before discontinuing, but also achieved SVR. Two patients had viral breakthroughs at 12 weeks and 24 weeks of treatment.Two patients were lost to follow up and were undetectable at last assessment. In total, 8/10 patients for whom results are available, achieved SVR. The side effect profile observed during the post-study dosing was consistent with the expected profile of Peg-IFN/RBV therapy.
Conclusions: The rapid and substantial initial antiviral effect of telaprevir was maintained by the majority of patients during post-study therapy with PegIFN/RBV. The observation that SVR was achieved in eight patients, including 1 who completed only 22 weeks of treatment, suggests that telaprevir-based regimens may allow increased SVR rates as compared to current therapies.
M. Rodriguez-Torres1; E. J. Lawitz2; J. G. McHutchison3
1. Fundacion de Investigacion de Diego, Santurce, PR, USA.
2. Alamo Medical Research, San Antonio, TX, USA.
3. Duke Clinical Research Institute & Division of Gastroenterology, Duke University, Durham, NC, USA.
Purpose: Telaprevir (TVR, VX-950) is an orally administered, highly selective peptidomimetic inhibitor of the Hepatitis C virus (HCV) NS3-4A protease. The VX05-950-102 study was designed to assess the safety of telaprevir when given in combination with Peginterferon alfa-2a (Peg-IFN) and ribavirin (RBV) and to evaluate the antiviral response during 28 days of dosing. After completion of the 28-day study, all subjects received off-study therapy with Peg-IFN/RBV under the clinical care of their physicians. Here we report the outcome of treatment after this post-study therapy.
Methods: This study included 12 treatment-naïve, mostly Latino (10/12),patients infected with genotype 1. All subjects received TVR (750 mg q8h), Peg-IFN alfa-2a (180 µg weekly), and RBV (1000 or 1200 mg daily). At the completion of the 28 days, patients began off-study follow-on therapy with Peg-IFN alfa -2a/RBV.
Results: TVR/Peg-IFN/RBV was well tolerated in the 28-day study, with no serious adverse events. The adverse event profile was consistent with the profile commonly seen with Peg-IFN/RBV therapy. All subjects demonstrated a response to the study drug regimen, with 2 subjects reaching undetectable (< 10 IU/mL, Roche Taqman® Assay) levels of plasma HCV RNA within 8 days of the start of dosing, and all subjects had undetectable HCV RNA at the end of the 28-day study dosing period. At 12 weeks of follow-on therapy after completing the 28-day study dosing, 11 subjects had undetectable HCV RNA. All subjects continued on Peg-IFN/RBV therapy, and were followed for response in accordance with standard practice. Seven patients received a total of 48 weeks of treatment and achieved SVR. One patient received Peg-IFN/RBV for only 18 weeks (total treatment 22 weeks) before discontinuing, but also achieved SVR. Two patients had viral breakthroughs at 12 weeks and 24 weeks of treatment.Two patients were lost to follow up and were undetectable at last assessment. In total, 8/10 patients for whom results are available, achieved SVR. The side effect profile observed during the post-study dosing was consistent with the expected profile of Peg-IFN/RBV therapy.
Conclusions: The rapid and substantial initial antiviral effect of telaprevir was maintained by the majority of patients during post-study therapy with PegIFN/RBV. The observation that SVR was achieved in eight patients, including 1 who completed only 22 weeks of treatment, suggests that telaprevir-based regimens may allow increased SVR rates as compared to current therapies.
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