Boehringer Ingelheim’s investigational faldaprevir achieved viral cure in 88% of treatment-naive hepatitis C patients in Asia

INGELHEIM, Germany I June 8, 2013 I 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.⁶ This 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 it is the first significant Phase III sub-analysis for an HCV protease inhibitor in patients in this region,” said Professor Masao Omata, Professor of Gastroenterology, University of Tokyo 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.¹ Elevations 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

NOTES TO EDITORS

About STARTVerso™1 and 2
STARTVerso™1 and 2 are double-blind, placebo-controlled Phase III trials of faldaprevir⁺ in combination with PegIFN/RBV. The studies enroled and treated 1,310 (652 in STARTVerso™1 and 658 in STARTVerso™2) treatment-naïve patients who were infected with chronic genotype-1 hepatitis C. STARTVerso™1 included patients from Europe and Japan; STARTVerso™2 included patients from USA, Canada, Taiwan and Korea. Patients were randomised to receive a once-daily dose of 120mg faldaprevir⁺, 240mg faldaprevir⁺ or placebo in addition to PegIFN and RBV.

Treatment duration depended on whether patients met criteria for protocol-defined early treatment success (ETS) (week 4 below limit of quantification [BLQ] and week 8 below limit of detection [BLD]). All patients who met these criteria received 12 weeks of faldaprevir⁺ with 24 weeks of PegIFN/RBV. Patients who did not meet the criteria were re-randomised to receive 24 weeks of faldaprevir⁺ or 12 weeks of faldaprevir⁺ followed by 12 weeks of placebo in the 120mg dose group or 12 weeks of faldaprevir⁺ in the 240mg dose group; both groups received 48 weeks of PegIFN/RBV. Patients in the control arm received 24 weeks of placebo with 48 weeks of PegIFN/RBV.

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.⁸ Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,⁹ with 3-4 million new cases occurring each year.¹⁰

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.¹¹ 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.¹² Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.¹²

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 core component 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 STARTVerso^TM trial programme, which includes treatment-naïve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.

Deleobuvir (BI 207127) is a potent investigational non-nucleoside NS5B polymerase inhibitor, specifically optimised to treat patients with genotype-1b hepatitis C virus. Phase III HCVerso^TM trials, investigating the interferon-free regimen of deleobuvir in combination with faldaprevir⁺ and ribavirin, are well underway.

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 combination is part of the company’s continued exploration to discover and develop innovative options for the treatment of HCV.

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.

⁺faldaprevir is an investigational compound and not yet approved. Its safety and efficacy have not yet been fully established
*Criteria for shortened treatment duration is early treatment success = week 4 HCV below limit of quantification [BLQ] and week 8 HCV below limit of detection [BLD]