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Investigational interferon-free regimen demonstrates undetectable hepatitis C virus in all patients reaching end of treatment in ongoing Phase II trial: BI/Presidio Faldaprevir + PPI-668 + Deleobuvir
  · Collaborative trial from Boehringer Ingelheim and Presidio Pharmaceuticals investigates triple-DAA regimen of faldaprevir, deleobuvir and PPI-668
· 97% (28/29) of patients achieved rapid virologic response at 4 weeks and 100% of patients (13/13) who have completed all 12 weeks of the investigational regimen had undetectable levels of hepatitis C virus at the end of treatment
· Of the 36 genotype-1a patients, the majority have a non-CC IL28B genotype and many have pre-existing HCV mutations that had been difficult-to-cure in previous studies
For media outside of the U.S.A., UK and Canada only
INGELHEIM, 8 October, 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 genotype1; 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.


Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim "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 HCVersoª 1 and 2 trials. The trials are evaluating the treatment regimen of faldaprevir*, deleobuvir* and ribavirin in genotype-1b infected patients. NOTES TO EDITORS
About the Phase IIa Presidio collaboration trial The trial includes 36 treatment-na•ve patients with genotype-1a HCV treated for 12 weeks with an all-oral DAA regimen, with 24 weeks of post-treatment follow-up. There are three arms in this study:2
· The first enrolled 12 patients and is evaluating faldaprevir* 120 mg once-daily (QD), PPI-668 200mg once-daily (QD) and deleobuvir* 600mg twice-daily (BID) with ribavirin
· The second enrolled 12 patients and is evaluating faldaprevir* 120 mg QD, PPI-668 200mg QD and deleobuvir* 400mg BID with ribavirin
· The third arm enrolled 12 patients and is evaluating the same regimen as arm 1, but without ribavirin The primary endpoint of the trial is viral cure 12 weeks after treatment completion (SVR12).2
The Boehringer Ingelheim NewsHome: An innovative resource for journalists The Boehringer Ingelheim hepatitis C www.NewsHome.com is the one-stop-shop for clear, concise and easy to understand information about hepatitis C for the media.
About Boehringer Ingelheim in hepatitis C
Through pioneering science, Boehringer Ingelheim is striving to find answers to the pressing challenges still faced by the diverse population of hepatitis C patients. The company's comprehensively designed hepatitis C clinical trial programme includes a broad range of patients, including the challenging to cure, that clinicians see every day in clinical practice.
Boehringer Ingelheim is developing faldaprevir*, an optimised second generation protease inhibitor, as the foundation for both interferon-based and interferon-free treatment regimens.
Interferon-based therapy with faldaprevir* has the potential to improve cure rates with the added convenience of once-daily dosing and no dietary requirements for intake. Faldaprevir* has proven efficacy in a broad range of genotype-1a and 1b hepatitis C patients. The Phase III STARTVersoª trial programme, which includes treatment-na•ve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.4,5,6,7 Deleobuvir* is a potent investigational non-nucleoside NS5B polymerase inhibitor to treat patients with genotype-1b hepatitis C virus. Phase III HCVersoª trials, investigating the interferon-free regimen of twice-daily deleobuvir in combination with once-daily faldaprevir* and ribavirin, are well underway.8,9 As part of Boehringer Ingelheim's long-term commitment to hepatitis C, the company is also evaluating other combinations of investigational hepatitis C compounds that work in different ways. Boehringer Ingelheim's recent collaboration with Presidio Pharmaceuticals, Inc. for a Phase II clinical study investigating an interferon-free, all-oral, potentially ribavirin-free combination is part of the company's continued exploration to discover and develop innovative options for the treatment of HCV.
About Hepatitis C
Hepatitis C is a blood-borne infectious disease caused by the hepatitis C virus which lives and replicates in the liver. Hepatitis C is a leading cause of chronic liver disease, liver cancer and transplantation.10 Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,11 with 3-4 million new cases occurring each year.12
It is common for hepatitis C patients to remain undiagnosed due to the initial unspecific symptoms of the disease. Consequently, a large number of patients first present to their physician when they experience symptoms or already have liver disease.13 Patients with advanced liver disease are challenging to cure, yet have the greatest need for more effective and better tolerated treatments. Of patients with chronic hepatitis C, 20 percent will develop liver cirrhosis, of which 2-5 percent will die every year.14 Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.14
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.
Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim's endeavors.
In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales.
About Presidio in HCV
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company focused on the discovery and development of oral pan-genotypic therapeutics for HCV patients. Efforts are currently focused on novel inhibitors of both the HCV NS5A and NS5B genes. PPI-668 is an investigational, pan-genotypic, once daily, NS5A inhibitor. In earlier clinical studies in healthy volunteers and HCV-infected patients, PPI-668 has been well-tolerated to date with no serious or severe adverse events and no apparent pattern of treatment-related clinical side effects or laboratory abnormalities. PPI-668 achieves plasma concentrations high enough to inhibit most pre-existing resistant variants and achieves steady-state levels after a single dose. In a clinical study of PPI-668 monotherapy in GT1 HCV-infected patients, viral load reductions of 3.5 to 3.7 log10 HCV were achieved in 1-2 days. Activity was also noted in GT3 HCV-infected patients.
Presidio's NS5B inhibitor, PPI-383, is a novel pan-genotypic non-nucleosidic inhibitor with potential to inhibit all of the major HCV genotypes.This compound is currently in Phase 1 studies in healthy subjects. For more information, please visit our website at: www.presidiopharma.com.
* Faldaprevir, deleobuvir and PPI668 are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.
1 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 2 ClinicalTrials.gov. Study of PPI-668, BI 207127 and Faldaprevir, With and Without Ribavirin, in the Treatment of Chronic Hepatitis C. May 2013.
3 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.
4 ClinicalTrials.gov. Efficacy and Safety of BI 201335 in Combination With Pegylated Interferon-alpha and Ribavirin in Treatment-na•ve Genotype 1 Hepatitis C Infected Patients. http://clinicaltrials.gov/ct2/show/NCT01343888?term=bi+201335&rank=4 [Last accessed 17/09/13]
5 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]
6 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]
7 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]
8 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]
9 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]
10 World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf
[Last accessed on 23/09/13
11Centers 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]
12 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]
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]
14 Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease 2009; 48:313-20

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