Phase III data show Boehringer Ingelheim's faldaprevir* was highly effective in a broad range of patients with genotype-1 hepatitis C including patients co-infected with HIV

Canada NewsWire

BURLINGTON, ON, Nov. 18, 2013

• Pivotal Phase III STARTVerso™ data show efficacy of faldaprevir^* in difficult-to-cure patient populations such as those with HIV co-infection and advanced liver disease
• 84 per cent of patients benefited from a shorter time on treatment and the majority went on to achieve viral cure, with no compromise on safety and tolerability (STARTVerso™1&2)ⁱ

BURLINGTON, ON, Nov. 18, 2013 /CNW/ - Boehringer Ingelheim today announced new data from its Phase III clinical trial program, STARTVerso™, which evaluates faldaprevir^*, a molecule discovered in Canada, in combination with pegylated interferon and ribavirin (PegIFN/RBV). Patients with genotype-1 (GT-1) hepatitis C (HCV) who have not received previous treatment (treatment-naïve: STARTVerso™1&2), treatment-experienced patients (STARTVerso™3), and HIV co-infected patients (STARTVerso™4) participated in this study program.^{ii, iii, iv} The results from these and additional studies were presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, which took place November 1 to 5 inWashington, D.C.

In STARTVerso™1&2, 84 per cent of treatment-naïve patients receiving faldaprevir^* were able to shorten total time on treatment from 48 to 24 weeks; 83 per cent of these patients achieved viral cure (SVR12^).^v Overall, 73 per cent and 72 per cent of patients achieved SVR12 with faldaprevir^* 120mg and 240mg regimens respectively.^vi Interim results from STARTVerso™4 showed that 74 per cent of patients with HCV/HIV co-infection treated with faldaprevir^* had undetectable HCV 4 weeks after the conclusion of treatment (SVR4); a response rate similar to that seen with HCV mono-infection.^vii Additionally, treatment of difficult-to-cure patients who have relapsed on previous HCV treatment (STARTVerso™3) demonstrated viral cure rates of 70 per cent with faldaprevir^*after 12 weeks.^viii In the same study, patients who partially responded and those who showed no response to previous treatment achieved viral cure rates of up to 58 per cent and 33 per cent, respectively after 12 weeks.^ix

"A broad range of patients have been effectively treated in the STARTVerso™ trials, reinforcing the potential benefits of faldaprevir^* as an effective treatment for hepatitis C patients with genotype-1," said Dr. Curtis Cooper, associate professor of medicine and director of viral hepatitis program at the University of Ottawa. "These and other STARTVerso™ data suggest that faldaprevir^*may be a promising future treatment for hepatitis C."

More than 2,200 patients have been studied in the STARTVerso™ trial program, including patients with difficult-to-cure types of HCV:

• Over 300 patients (14 per cent) in the program have HCV/HIV co-infection; these patients have higher levels of HCV in their blood and can be more difficult to cure.^{x, xi}
• 677 patients (31 per cent) were treatment-experienced, meaning they had attempted previous HCV treatment but did not achieve viral cure.^xii
• 40 per cent of patients (approximately 271 patients) in STARTVerso™3 had advanced liver disease (≥F3 fibrosis).^xiii
• 59 per cent of patients (approximately 775 patients) in STARTVerso™1&2 had a non-CC IL28B genotype; in previous studies, these patients were less likely to achieve viral cure.^{xiv, xv}

In the STARTVerso™ clinical trial program, adverse events (AEs) were generally mild and well manageable. Most common AEs included jaundice due to transient bilirubin elevation (unconjugated hyperbilirubinemia), nausea, fatigue, rash, diarrhea, headache, anemia and rash. ^{xvi, xvii, xviii} Ninety-five per cent of patients completed faldaprevir^* treatment.^{xix, xx, xxi}

Summary of adverse events in the STARTVerso™ clinical trial program

STARTVerso™1&2^xxii

In the study, the most common AEs were gastrointestinal events and anemia, occurring in 7/11/18 per cent and 14/14/13 per cent of patients treated with PegIFN/RBV plus placebo, 120mg/240mg faldaprevir^* regimens respectively. Transient benign bilirubin elevation (unconjugated hyperbilirubinemia) occurred in 1/12/46 percent of patients respectively.

STARTVerso™3^xxiii

AEs of at least moderate intensity included gastrointestinal side effects, which occurred in 6 per cent, 20 per cent and 17 per cent of patients in the PegIFN/RBV plus placebo, 12- and 24-week faldaprevir^* arms respectively. Also, anemia occurred in 5 per cent of patients in the PegIFN/RBV plus placebo arm and 10 per cent of patients in both faldaprevir^* arms.

STARTVerso™4^xxiv

The most common AEs in the study were nausea, fatigue and diarrhea, occurring in 28 per cent and 44 per cent; 32 per cent and 35 per cent; and 25 per cent and 28 per cent with the 120mg and 240mg faldaprevir^* regimens respectively.

Phase III STARTVerso™ results

STARTVerso™1&2^xxv

Treatment-naïve patients were randomized 1:2:2 to receive 48 weeks of PegIFN/RBV plus placebo (Arm 1); faldaprevir^* 120mg once-daily for 12 or 24 weeks (Arm 2); or faldaprevir^* 240mg once-daily for 12 weeks (Arm 3). SVR12 rates were:

• Arm 1: 50 per cent (131/264)
• Arm 2: 73 per cent (382/521)
• Arm 3: 72 per cent (378/524)

Patients in arms 2 and 3 stopped all treatment at week 24 if HCV RNA <25IU/mL was detected or undetected at week 4 and undetected at week 8 of treatment. Results were:

• Arm 2: 84 per cent (436/521) of which 83 per cent (362/436) achieved SVR12
• Arm 3: 84 per cent (441/524) of which 83 per cent (368/441) achieved SVR12

STARTVerso™3^xxvi

The trial included 3 cohorts of treatment-experienced patients who had: prior relapse (cohort 1), prior partial response (cohort 2) and prior null response (cohort 3).

Cohort 1

Patients were randomized 1:2:2 to receive 48 weeks of PegIFN/RBV plus placebo (placebo); faldaprevir^* 240mg once-daily for 12 weeks (FDV12W); or faldaprevir^* 240mg once-daily for 24 weeks (FDV24W). SVR12 rates were:

• Placebo: 14 per cent (7/49)
• FDV12W: 70 per cent (69/99)
• FDV24W: 70 per cent (71/102)
• 87 per cent of patients stopped all treatment at week 24 of whom 75 per cent achieved SVR12

Cohort 2

Patients were randomized 1:2:2 to receive 48 weeks of PegIFN/RBV plus placebo (placebo); faldaprevir^* 240mg once-daily for 12 weeks (FDV12W); or faldaprevir^* 240mg once-daily for 24 weeks (FDV24W). SVR12 rates were:

• Placebo: 3 per cent (1/29)
• FDV12W: 58 per cent (33/57)
• FDV24W: 47 per cent (26/55)

Cohort 3

Patients were randomized 1:1 to receive faldaprevir^* 240mg once-daily for 12 weeks (FDV12W) or faldaprevir^* 240mg once-daily for 24 weeks (FDV24W) with PegIFN/RBV for 48 weeks. SVR12 rates were:

• FDV12W: 33 per cent (48/145)
• FDV24W: 33 per cent (46/141)

STARTVerso™4^xxvii

The ongoing trial includes patients co-infected with HCV and HIV who are HCV treatment-naïve or have relapsed after previous HCV therapy. Patients received 48 weeks of PegIFN/RBV plus either faldaprevir^* 120mg once-daily for 24 weeks (Arm A); or faldaprevir^* 240mg once-daily for 12 or 24 weeks (dependent on randomization at week 12) (Arm B). SVR4 rates were:

• Arm A: 72 per cent (89/123)
• Arm B, faldaprevir^* 12 weeks: 79 per cent (66/84)
• Arm B, faldaprevir^* 24 weeks: 84 per cent (72/86)
• Arm B, total: 76 per cent (140/185^a)
• Total: 74 per cent (229/308)

^aincludes additional patients from 240mg treatment group who discontinued prior to week 12

Patients in whom HCV RNA <25IU/mL was detected or undetected at week 4 and undetected at week 8, were randomized 1:1 to stop treatment at week 24 or continue PegIFN/RBV to 48 weeks. Results were:

• Arm A: 77 per cent (95/123) of which 89 per cent (85/95) achieved SVR4
• Arm B, total: 81 per cent (150/185) of which 87 per cent (131/150) achieved SVR4
• Total: 80 per cent (245/308) of which 88 per cent (216/245) achieved SVR4

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program, HCVerso™, is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. The HCVerso™ program includes the pivotal STARTVerso™ and HCVerso™ clinical trial programs.

Faldaprevir^*, also known as BI 201335, an investigational, oral protease inhibitor discovered in Canada is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir^* as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. The Phase III STARTVerso™ trial program, which includes treatment-naïve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.

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 leading cause of chronic liver disease, liver cancer and transplantation that affects approximately 170 million people globally.^xxviii In Canada, an estimated 240,000 individuals, with some estimates as high as 400,000 are infected with the disease.^xxix The Canadian Liver Foundation estimates that since 2007 approximately 500 people die from hepatitis C-related illnesses inCanada each year.^xxx The number of hepatitis C-associated illnesses, including cirrhosis, liver failure, liver death and the need for liver transplants will likely double or triple in the next decade.^xxxi

Of patients with chronic hepatitis C, 20 per cent will develop liver cirrhosis, of which 2 to 5 per cent will die every year.^xxxii

About Boehringer Ingelheim (Canada) Ltd.
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 44,000 employees.

Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine. As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. 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 endeavours.

In 2011, Boehringer Ingelheim posted net sales of 13.2 billion euro while spending almost 24 per cent of net sales in its largest business segment Prescription Medicines on research and development. The Canadian headquarters of Boehringer Ingelheim was established in 1972 and is home to more than 750 employees across the country. For more information please visitwww.boehringer-ingelheim.ca.

References

ⁱ Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
ⁱⁱ Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
ⁱⁱⁱ Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^iv Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^v Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^vi Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
^vii Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013
^viii Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^ix Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^x Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xi Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010; 139:120-9
^xii Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xiii Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xiv Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
^xv Thompson AJ, Muir AJ, Sulkowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010; 139:120-9.
^xvi Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
^xvii Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xviii Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xix Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
^xx Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxi Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxii Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxiii Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxiv Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxv Jensen, D. et al. A pooled analysis of two randomized, double-blind placebo-controlled Phase III    trials (STARTVerso1&2) of faldaprevir plus pegylated interferon alfa-2a and ribavirin in treatment- naïve patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the  64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 -5 November, 2013.
^xxvi Jacobson, I. et al. STARTVerso3: A randomized, double-blind, placebo-controlled Phase III trial of faldaprevir in combination with pegylated interferon alfa-2a and ribavirin in treatment-experienced patients with chronic hepatitis C genotype-1 infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxvii Rockstroh, J. et al.  STARTVerso 4 Phase III trial of faldaprevir plus peg interferon alfa-2a and ribavirin (PR) in patients with HIV and HCV genotype 1 co-infection. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 - 5 November, 2013.
^xxviii World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 21/10/13].
^xxix Sherman, M et al. Liver disease in Canada: A crisis in the making. Report by Canadian Liver Foundation. From web site. 2013.
^xxx Sherman, M et al. Liver disease in Canada: A crisis in the making. Report by Canadian Liver Foundation. From web site.
^xxxi Zou, S. et al. Epidemiology and Health Care Planning: Estimating the Burden of Hepatitis C in Canada. Health Canada.
^xxxii Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease 2009; 48:313-20.

^*Faldaprevir is an investigational compound. Its safety and efficacy has not yet been fully established and it is currently not authorized for sale in Canada.
^SVR12 = sustained viral response 12 weeks after treatment completion, also described as "viral cure".

SOURCE Boehringer Ingelheim (Canada) Ltd.

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