Boehringer Ingelheim’s interim data from Phase II HCV clinical collaboration with Presidio Pharmaceuticals accepted for presentation at AASLD

Download PDF Copy

Oct 8 2013

Boehringer Ingelheim today announced that interim data from its Phase II hepatitis C (HCV) clinical collaboration with Presidio Pharmaceuticals have been accepted for presentation as a late breaker poster at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place 1-5 November in Washington, D.C. (1) The poster presentation will be on Monday 4 November.

This ongoing study evaluates a new 12-week interferon-free regimen of Boehringer Ingelheim’s protease inhibitor, faldaprevir^*, and non-nucleoside NS5B polymerase inhibitor, deleobuvir^*, in combination with Presidio’s pan-genotypic HCV NS5A inhibitor, PPI-668^*, with and without ribavirin. (1,2) The trial is fully enrolled (36 patients) and to date, 97% of patients (28/29) have achieved undetectable levels of virus at week 4 of treatment, also known as rapid viral response (RVR). Additionally, 100% of patients who have completed treatment (13/13) achieved undetectable levels of virus at the end of treatment.

“These results are promising particularly because they show the potential to evaluate harder-to-treat populations; all patients studied were genotype-1a and the majority of patients had the non-CC IL28B genotype,” said Jacob Lalezari, M.D., Director of Quest Clinical Research in San Francisco, CA.

Two thirds of patients in the study have the difficult-to-cure non-CC IL28B genotype(1); previous studies have shown that presence of this genotype led to a reduced likelihood of achieving viral cure.(3) In addition, of the 29 patients who have completed 4 weeks treatment, 11 had HCV NS5A and/or NS5B resistance substitutions which are mutations in the hepatitis C virus that can impact treatment response with some antiviral therapies.(1) Ten of these patients achieved RVR and one patient had a partial response to treatment but developed viral breakthrough and was discontinued.

“This collaboration is part of our ongoing commitment to develop interferon-free treatment options for a broad range of real-world patients, including the difficult-to-cure who currently have few treatment options,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “This data adds to the growing body of evidence for faldaprevir^* which is the foundation of both, our interferon-based and interferon-free treatment regimens. We are encouraged by the data so far and look forward to further results at AASLD next month and the final results in Q2 2014.”

To date, there have been no treatment discontinuations for adverse events in this study. Adverse events overall have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir^* and deleobuvir^*.(1)

In March 2013, Boehringer Ingelheim and Presidio Pharmaceuticals entered a non-exclusive collaboration to evaluate the three direct acting antivirals (DAAs) in combination regimens. Both companies will retain all rights to their respective compounds. Presidio has operational responsibility for this collaborative trial, with oversight by an intercompany project team. Post-treatment sustained response data will be presented at the AASLD Congress next month and final results are expected in Q2 2014.

As part of the company’s long-term commitment to developing new therapeutic options for patients with HCV, Boehringer Ingelheim recently completed enrolment for its pivotal Phase III interferon-free HCVerso™ 1 and 2 trials. The trials are evaluating the treatment regimen of faldaprevir^*, deleobuvir^* and ribavirin in genotype-1b infected patients.

References

J. Lalezari. Rapid and Consistent Virologic Responses in a Phase 2 Trial of a New All-Oral Combination of Faldaprevir, Deleobuvir, and PPI-668, with and without Ribavirin, in Patients with HCV Genotype-1a Infection
ClinicalTrials.gov. Study of PPI-668, BI 207127 and Faldaprevir, With and Without Ribavirin, in the Treatment of Chronic Hepatitis C. May 2013. http://clinicaltrials.gov/ct2/show/NCT01859962?term=ppi-668&rank=2 [last accessed 07/10/13]
A. Thompson. Interleukin-28B Polymorphism Improves Viral Kinetics and Is the Strongest Pretreatment Predictor of Sustained Virologic Response in Genotype 1 Hepatitis C Virus. 2010.
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 17/09/13]
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 17/09/13]
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 17/09/13]
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 17/09/13]
ClinicalTrials.gov. IFN-free Combination Therapy in HCV-infected Patients Treatment-naive: HCVerso1. http://clinicaltrial.gov/ct2/show/NCT01732796?term=faldaprevir+bi+207127&rank=3 [Last accessed 17/09/13]
ClinicalTrials.gov. Phase 3 Study of BI 207127 in Combination With Faldaprevir and Ribavirin for Treatment of Patients With Hepatitis C Infection, Including Patients Who Are Not Eligible to Receive Peginterferon: HCVerso2. http://clinicaltrial.gov/ct2/show/NCT01728324?term=faldaprevir+bi+207127&rank=2 [Last accessed 17/09/13]
World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 23/09/13
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 23/09/13]
World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 16/09/13]
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 16/09/13]
Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease 2009; 48:313–20