BERLIN--(BUSINESS WIRE)--MSD reported that final results from a Phase III study of 'Victrelis'™ (boceprevir), its investigational oral hepatitis C protease inhibitor, added to peginterferon alfa-2a ('Pegasys'®) marketed by Roche Products Limited, and ribavirin therapy (PR) were presented for the first time today as part of a late-breaker poster session at The International Liver Congress™ / 46th European Association for the Study of the Liver (EASL) annual meeting.
Over the 48 week treatment period, nearly two thirds (64 percent (86/134)) of treatment-failed patients who were receiving boceprevir in addition to PR for chronic hepatitis C virus (HCV) genotype 1, achieved cure rates or sustained virologic response (SVR) compared to 21 percent (14/67) who achieved SVR on standard care alone,(p<0.0001).i In addition fewer patients receiving boceprevir relapsed after the end of treatment, 12 percent (11/95) versus 33 percent (7/21) for control.i
The presentation of these new analyses coincide with the publication of the primary data from the pivotal Phase III studies for boceprevir, HCV RESPOND-2 and HCV SPRINT-2, in today's edition of The New England Journal of Medicine.
"In this study, the addition of boceprevir to peginterferon alfa-2a and ribavirin resulted in approximately a three-fold increase in sustained virologic response in patients who were previous nonresponders or relapsers to standard hepatitis C therapy.i" said Steven L. Flamm, M.D., professor in medicine-hepatology and surgery, Northwestern University Feinberg School of Medicine, Chicago. "These results are similar to those seen with the 48-week treatment regimen of boceprevir added to peginterferon alfa-2b and ribavirin in HCV RESPOND-2, a pivotal Phase III study.ii Taken together, these studies showed that boceprevir combined with either peginterferon alfa-2a or alfa-2b and ribavirin achieved significantly higher SVR rates in chronic HCV genotype 1 patients who failed prior therapy compared to peginterferon and ribavirin alone."
The five most common treatment-emergent adverse events in the study reported for patients receiving boceprevir added to PEG2a/R and control, respectively, were: fatigue (50 and 54 percent), anaemia (50 and 33 percent), nausea (39 and 27 percent), dysgeusia (39 and 15 percent) and headache (28 and 31 percent). Neutropenia was reported more frequently in patients receiving boceprevir compared to control (31 and 18 percent, respectively). Serious adverse events were reported in 13 and 10 percent of patients in the study groups, respectively.i Treatment discontinuations due to adverse events over the total course of treatment were 17 percent and 4 percent, respectively. Erythropoietin (EPO) for management of anaemia was allowed at the discretion of the investigator per the study protocol, and was used by 47 and 30 percent of patients in the study groups, respectively.i
Possible Predictors of Sustained Virologic Response
Four-Week Lead-In Period
New data, also presented at EASL, identified potential predictors for the likelihood of achieving SVR based on a patient's response during a four-week lead-in period with PR alone prior to the addition of boceprevir, as well as the genetic marker IL28B.
| Sustained Virologic Response (SVR, %) | ||||||||
| HCV SPRINT-2 (treatment naïve patients) iii |
'Good Response' after 4-week lead in (greater than or equal to 1.0-log10 decline in HCV-RNA) |
'Poor Response' after 4-week lead in (less than 1.0-log10 decline in HCV-RNA) |
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| Boceprevir RGT* | 81 (203/252) | 28 (27/97) | ||||||
| Boceprevir 48 weeks | 79 (200/254) | 38 (36/95) | ||||||
| Standard care (PR) | 51 (133/260) | 4 (3/83) | ||||||
| HCV RESPOND-2 (treatment-failure patients) iii | ||||||||
| Boceprevir RGT* | 73 (80/110) | 33 (15/46) | ||||||
| Boceprevir 48 weeks | 79 (90/114) | 34 (15/44) | ||||||
| Standard care (PR) | 25 (17/67) | 0 (0/12) | ||||||
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*Response Guided Therapy |
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These analyses showed that 4-week lead-in response helped predict SVR in all three treatment groups, and the addition of boceprevir to the treatment regimen improved SVR rates regardless of whether patients had good or poor response during the lead-in period.iii
IL28B genotype
In pre-specified analyses of the pivotal Phase III studies, researchers found that IL28B status (CC, CT or TT) was a strong baseline predictor of viral response at treatment week 4, week 8 and SVR among patients receiving boceprevir.iv Among those carrying the CC gene allele, 89 percent of treatment-naïve patients and 82 percent of treatment-failure patients had an early response, defined by undetectable virus (HCV-RNA) at treatment week 8, and were eligible for a shorter duration of therapy. Among those with the less favourable gene allele (CT or TT), 52 percent of treatment-naïve patients and 48 percent of treatment-failure patients had an early response and were eligible for a shorter duration of therapy.iv The analyses also showed that response after the 4-week lead-in was a stronger predictor of SVR than any single baseline variable, including IL28B status.iv
The analyses included data from 63 percent of patients (912/1442) in the pivotal Phase III studies who received at least one dose of boceprevir or standard therapy and consented to genomic analysis to test for IL28B polymorphisms. In total, 28 percent of tested patients carried the CC allele, while 54 percent carried the CT allele and 18 percent carried TT.iv
Notes to Editor
SPRINT-2 and RESPOND-2 Methodology
In both studies, all patients receiving boceprevir were treated with a 4-week lead-in of PEGINTRON (1.5 mcg/kg/week) and an investigational dose of ribavirin (600-1,400 mg/day), followed by the addition of boceprevir (800 mg three times a day). ii,v In each study, patients were randomized to three groups: ii,v
- *Response-guided therapy (RGT), in which total treatment duration was based on certain early response criteria. Treatment-failure patients with undetectable virus (HCV-RNA) at week 8 were eligible to stop all treatment at 36 weeks. Treatment-naïve patients who had undetectable virus (HCV-RNA) during weeks 8 through 24 were eligible to stop all treatment at 28 weeks.
- 48 weeks of treatment, in which patients received a 4-week lead-in with PR followed by the addition of boceprevir for 44 weeks.
- Control, in which patients received PR for 48 weeks.
SVR, the protocol specified primary efficacy endpoint of the studies, is defined as achievement of undetectable HCV-RNA at 24 weeks after the end of treatment in all randomized patients treated with any study medication. Per protocol, if a patient did not have a 24-week post-treatment assessment, the patient’s 12-week post-treatment assessment was utilized.
About PEGINTRON
For further information on peginterferon alfa-2b, please refer to http://www.medicines.org.uk/EMC/medicine/10321/SPC/ViraferonPeg+Pen+50,+80,+100,+120+or+150+micrograms++powder+and+solvent+for+solution+for+injection+in+pre-filled+pen/.
About MSD
Merck Sharp & Dohme Limited is a subsidiary of Merck operating in the UK. Through our medicines, vaccines, biologic therapies, and consumer and animal products, Merck and its affiliates work with customers and operate in more than 140 countries to deliver innovative health solutions. For more information on Merck Sharp & Dohme Limited, please visit www.msd-uk.co.uk.
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References |
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i S. Flamm et al. High Sustained Virologic Response Among Genotype 1 Previous Non-responders and Relapsers to Peginterferon/Ribavirin when Re-treated With Boceprevir Plus Peginterferon Alfa-2a/Ribavirin . EASL Poster 1366 ii Bacon, B. R. et al. (2011). Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection. New England Journal of Medicine, 13, 1207-1217. iii Vierling J. et al. Four-Week Therapy With Peginterferon Alfa-2b/Ribavirin Effectively Predicts Sustained Virologic Response In Previously Untreated And Previous-Treatment-Failure Patients With HCV-1Treated With Boceprevir Plus Peginterferon Alfa-2b/Ribavirin. EASL Poster 418 iv Poordad F. et al. IL28b Polymorphism Predicts Virologic Response In Patients With Hepatitis C Genotype 1 Treated With Boceprevir Combination Therapy. EASL Presentation 2011. v Poordad, F.P. (2011). Boceprevir for Untreated Chronic HCV Genotype 1 Infection. N ENGL J Med Vol. 364;13, 1195-1206. |