Faldaprevir+ achieves viral cure in 88% of treatment-naïve genotype-1 hepatitis C patients in Asia

Download PDF Copy

Jun 10 2013

New findings presented today during the APASL Liver Week in Singapore, highlighted the efficacy and safety of faldaprevir⁺ plus pegylated interferon and ribavirin (PegIFN/RBV) in treatment-naïve patients with genotype-1 hepatitis C virus (HCV) in Asia.¹ This post-hoc sub-analysis of the Phase III STARTVerso™1 and 2 trials showed that both doses of faldaprevir were associated with high viral cure rates and a shorter treatment duration in this particular patient group.¹ The STARTVerso™1 and 2 trials are part of the global STARTVerso™ trial programme which includes four Phase III trials with more than 2,200 treatment-naïve, treatment-experienced and HIV co-infected patients with HCV.^2,3,4,5

The prevalence of HCV infection is particularly high in Asia and there remains a significant unmet need for effective treatment options.⁶This post-hoc sub-analysis included 243 patients with HCV from three Asian countries (Japan, Korea and Taiwan). The primary end point was viral cure 12 weeks after completion of treatment (SVR12). Key findings reveal that 88% (172/196) of patients treated with faldaprevir (FDV 120mg or 240mg) plus PegIFN/RBV achieved viral cure compared with 62% (29/47) treated with placebo plus PegIFN/RBV.¹ Even at the lower dose, 100% of patients from Taiwan (18/18) achieved viral cure when treated with faldaprevir (120mg) plus PegIFN/RBV.¹ Patients from Japan and Korea also achieved high viral cure rates of 85% (44/52) and 86% (25/29) respectively, with the 120mg dose. High efficacy was also seen with the higher 240mg dose of faldaprevir.¹

“These data are very encouraging for physicians and patients in Asia as there is a large population of treatment-naïve patients in this region in need of more effective treatment options,” said Professor Masao Omata, Yamanashi Central and Kita Hospitals, Yamanashi, Japan and lead author of the STARTVerso™ sub-analysis in Asia. “The results are particularly relevant given that HCV presents a huge health burden in Asia. The viral cure rates of close to 90% in patients infected with the difficult-to-cure genotype-1 HCV highlight the potential of faldaprevir to address this unmet medical need.”

Findings also showed 95% and 93% of patients who received faldaprevir⁺120mg and 240mg respectively plus PegIFN/RBV achieved Early Treatment Success (ETS) and were eligible for shorter total treatment duration of only 24 weeks.¹ ETS was determined by sufficiently low virus levels at week 4 and week 8 of treatment (as defined in the protocol*).Of those patients who achieved ETS, 91% (120mg) and 92% (240mg) of patients went on to achieve viral cure (SVR12).¹

In addition, both faldaprevir⁺ doses were well tolerated and adverse events that led to discontinuation of all study medications was 5% for 240mg faldaprevir⁺-treated patients and 3% for 120mg versus 2% for placebo-treated patients.¹ Rash (9%, 8%, 13%) and gastrointestinal side-effects (4%, 8%, 21%) were the most common Grade 2-4 adverse events in the placebo, faldaprevir⁺ 120mg and faldaprevir⁺ 240mg arms respectively.¹Elevations in unconjugated bilirubin were observed in all faldaprevir⁺ dose groups, but these were reversible and not accompanied by increases in liver enzymes. No incremental reduction in haemoglobin was observed compared with PegINF/RBV alone.¹

“These data add to the growing body of evidence for faldaprevir and reinforce the comprehensive nature of the STARTVerso™ clinical trial programme,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “Addressing the diversity of HCV patients worldwide is essential to drug development and individualised patient management in this field. We look forward to adding to our robust clinical data for faldaprevir with results from the STARTVerso™2, 3 and 4 studies.”

Overall results of the STARTVerso™1 study, which include patients from Europe and Japan, were presented at the International Liver Congress (ILC/EASL) in April 2013. Results show up to 80% of patients treated with faldaprevir⁺ and PegIFN/RBV achieved viral cure compared with 52% of patients treated with placebo plus PegIFN/RBV.⁷ At both doses (120mg and 240mg), 87% to 89% of patients met criteria to stop all treatment after 24 weeks and 86% to 89% of these patients went on to achieve SVR12.⁷ Faldaprevir⁺ was well tolerated at both doses; at the lower dose, side-effect related treatment discontinuation was similar to placebo.⁷

Additional results from the STARTVerso^TM programme are expected to be presented at large international meetings in 2013 and 2014; data from STARTVerso™2, which include patients from USA, Canada, Taiwan and Korea, and data from STARTVerso™3 and 4, investigating treatment-experienced and HIV co-infected HCV patients.^3,4,5

References

1. Omata, M. et al. Faldaprevir plus pegylated-interferon and ribavirin in chronic HCV genotype-1 treatment-naïve patients: subanalysis of patients from Japan, Taiwan and South Korea. Presented at APASL Liver Week, 6-10 June, 2013

2. ClinicalTrials.gov. Efficacy and Safety of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-naïve Genotype 1 Hepatitis C Infected Patients. http://clinicaltrials.gov/ct2/show/NCT01343888?term=bi+201335&rank=4 [Last accessed 28/05/13]

3. ClinicalTrials.gov. BI 201335 Used in Treatment Naive Patients Infected With Genotype 1 Chronic Hepatitis C Infection. http://clinicaltrials.gov/ct2/show/NCT01297270?term=bi+201335&rank=5 [Last accessed 28/05/13]

4. ClinicalTrials.gov. Pivotal Trial Treatment Experienced Patient Infected With Hepatitis C Virus (HCV) Genotype 1 (GT1). http://clinicaltrials.gov/ct2/show/NCT01358864?term=bi+201335&rank=14 [Last accessed 28/05/13]

5. ClinicalTrials.gov. Phase III Trial of BI 201335 in Treatment Naive (TN) and Relapser Hepatitis C Virus (HCV)- Human Immunodeficiency Virus (HIV) Coinfected Patients. http://clinicaltrials.gov/ct2/show/NCT01399619?term=bi+201335+HIV&rank=1 [Last accessed 28/05/13]

6. Sievert W, et al. A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 2011; 31(Suppl. 2):61-80

7. Ferenci, P. et al. Faldaprevir plus pegylated interferon alfa-2A and ribavirin in chronic HCV genotype-1 treatment-naïve patients: final results from STARTVerso1, a randomised, double blind, placebo-controlled Phase III trial. Presented at the International Liver CongressTM (ILC), The 48th Annual Meeting of the European Association for the Study of the Liver (EASL), 24-28 April, 2013

8. World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 28/05/13]

9. Centers for Disease Control and Prevention (2012) Hepatitis C available at: http://wwwnc.cdc.gov/travel/yellowbook/2012/chapter-3-infectious-diseases-related-to-travel/hepatitis-c.htm [Last accessed on 28/05/13]

10. World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 28/05/13]

11. Chen S.L., Morgan T.R. The Natural History of Hepatitis C Virus (HCV) Infection. Int J Med Sci 2006; 3:47-52. Available from http://www.medsci.org/v03p0047.htm [Last accessed on 28/05/13]

12. Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009