- 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% 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)1
- Second-generation protease inhibitor faldaprevir* is being investigated in combinations both with and without interferon
INGELHEIM, Germany I November 2, 2013 I Boehringer Ingelheim today announced new data from its Phase III clinical trial programme, STARTVerso™, which evaluates faldaprevir* 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),1 treatment-experienced patients (STARTVerso™3),2 and HIV co-infected patients (STARTVerso™4)3 participated in this study programme. The results from these and additional studies will be presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, taking place 1-5 November in Washington, D.C.
In STARTVerso™1&2, 84% of treatment-naïve patients receiving faldaprevir* were able to shorten the total time on treatment from 48 to 24 weeks; 83% of these patients achieved viral cure (SVR12).1 Overall, 73% and 72% of patients achieved SVR12 with faldaprevir* 120mg and 240mg regimens, respectively. Interim results from STARTVerso™4 showed that 74% 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.3 Additionally, treatment of difficult-to-cure patients who have relapsed on previous HCV treatment (STARTVerso™3) demonstrated viral cure rates of 70% with faldaprevir*.2 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% and 33%, respectively.3 For the full STARTVerso™ results, see notes to editors.
“These data are encouraging and reinforce the potential benefits of faldaprevir* as an effective treatment for genotype-1 infected HCV patients,” said Ira Jacobson, M.D., Chief of the Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York. “The broad populations studied in STARTVerso™ and the fact that very few patients discontinued treatment due to adverse events provides physicians with confidence in faldaprevir* as an important potential addition to the available agents for the treatment of hepatitis C.”
More than 2,200 patients have been studied in the STARTVerso™ trial programme, including patients with difficult-to-cure types of HCV:
- Over 300 patients in the programme have HCV/HIV co-infection;3 these patients have higher levels of HCV in their blood and can be more difficult to cure4
- 677 patients were treatment-experienced, meaning they had attempted previous HCV treatment but did not achieve viral cure2
- 40% of patients in STARTVerso™3 had advanced liver disease (≥F3 fibrosis)2
- 59% of patients in STARTVerso™1&2 had a non-CC IL28B genotype;1 in previous studies, these patients were less likely to achieve viral cure5
“The STARTVerso™ trial results are particularly promising given the inclusion of a broad range of patients and the similar success rates seen in both HCV mono and HCV/HIV co-infected patients. These data will form the basis of regulatory submissions and we look forward to the outcome,” said Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim. “Faldaprevir* may offer a simple and convenient option for patients, due to once-daily dosing and no food restrictions. Faldaprevir* is the foundation of our HCV pipeline and we look forward to presenting pivotal Phase III HCVerso® data for the treatment of HCV as part of an interferon-free regimen in 2014.”
Faldaprevir* as part of this interferon-based regimen is likely to offer advantages over first generation protease inhibitors with fewer skin reactions, gastrointestinal events and no additional anaemia. In the STARTVerso™ clinical trial programme, adverse events (AEs) were generally mild and well manageable. Most common AEs included jaundice due to transient bilirubin elevation (unconjugated hyperbilirubinemia), nausea, fatigue, diarrhoea, headache, anaemia and rash. 95% of patients completed faldaprevir* treatment.1,2,3 For full STARTVerso™ results, see notes to editors.
ADDITIONAL BOEHRINGER INGELHEIM DATA AT THE MEETING
Faldaprevir* in further clinical settings
Further studies adding to the robust portfolio of evidence for faldaprevir* will be presented at the meeting. These include studies exploring drug-drug interactions in patients who are taking oral birth control pills and common medication to treat drug dependence and studies evaluating faldaprevir* in patients who have renal impairment.
Faldaprevir* as part of an interferon-free regimen
Additional news from Boehringer Ingelheim was released today featuring data from the collaborative trial with Presidio Pharmaceuticals. The ongoing Phase II trial investigating the regimen of faldaprevir*, deleobuvir* and PPI-668 (with and without ribavirin) in genotype-1a infected patients was accepted as late breaker and will be presented on Monday.
NOTES TO EDITORS
Phase III STARTVerso™ results
STARTVerso™1&2
Treatment-naïve patients were randomised 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:1
- Arm 1: 50% (131/264)
- Arm 2: 73% (382/521)
- Arm 3: 72% (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:1
- Arm 2: 84% (436/521) of which 83% (362/436) achieved SVR12
- Arm 3: 84% (441/524) of which 83% (368/441) achieved SVR12
In the study, the most common AEs were gastrointestinal events and anaemia, occurring in 11%/18% and 14%/13% of patients treated with 120mg/240mg faldaprevir* regimens respectively. Hyperbilirubinemia occurred in 12% and 46% of patients, respectively.1
STARTVerso™3
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).2
Cohort 1
Patients were randomised 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:2
- Placebo: 14% (7/49)
- FDV12W: 70% (69/99)
- FDV24W: 70% (71/102)
- 87% of patients stopped all treatment at week 24 of whom 75% achieved SVR12
Cohort 2
Patients were randomised 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:2
- Placebo: 3% (1/29)
- FDV12W: 58% (33/57)
- FDV24W: 47% (26/55)
Cohort 3
Patients were randomised 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:2
- FDV12W: 33% (48/145)
- FDV24W: 33% (46/141)
AEs of at least moderate intensity included gastrointestinal side effects, which occurred in 20% and 17% of patients in the 12- and 24-week faldaprevir* arms respectively. Also, anemia occurred in 10% of patients in both faldaprevir* arms.2
STARTVerso™4
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 randomisation at week 12) (Arm B). SVR4 rates were:3
- Arm A: 72% (89/123)
- Arm B, faldaprevir* 12 weeks: 79% (66/84)
- Arm B, faldaprevir* 24 weeks: 84% (72/86)
- Arm B, total: 76% (140/185a)
- Total: 74% (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 randomised 1:1 to stop treatment at week 24 or continue PegIFN/RBV to 48 weeks. Results were:3
- Arm A: 77% (95/123) of which 89% (85/95) achieved SVR4
- Arm B, total: 81% (150/185) of which 87% (131/150) achieved SVR4
- Total: 80% (245/308) of which 88% (216/245) achieved SVR4
The most common AEs in the study were nausea, fatigue and diarrhoea , occurring in 28% and 44%; 32% and 35%; and 25% and 28% with the 120mg and 240mg faldaprevir* regimens respectively.3
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 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 those with the most challenging types of HCV to cure that clinicians see every day in clinical practice.
Boehringer Ingelheim is developing faldaprevir*, an investigationalsecond generation protease inhibitor, in combinations both with and without interferon.
Interferon-based therapy with faldaprevir* has the potential to improve cure rates with the added convenience of once-daily dosing and no food restrictions. In clinical trials, faldaprevir* has shown efficacy in a broad range of genotype-1a and 1b hepatitis C patients. The Phase III STARTVerso™ trial programme, which includes treatment-naïve, treatment-experienced and HIV co-infected patients with hepatitis C virus, is nearly complete.
Deleobuvir* is a potent investigational non-nucleoside NS5B polymerase inhibitor to treat patients with genotype-1b hepatitis C virus. Phase III HCVerso® trials, investigating the interferon-free regimen of twice-daily deleobuvir* in combination with once-daily 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, 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.6 Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people,7 with 3-4 million new cases occurring each year.8
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.9 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.10 Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.10
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.
References
1Jensen, 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
2Jacobson, 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
3Rockstroh, 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: end of treatment response. Presented at The Liver Meeting®, the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD),1 – 5 November, 2013
4Rodriguez-Torres M. Focus on drug interactions: the challenge of treating hepatitis C virus infection with direct acting antiviral drugs in the HIV-positive patient. Curr Opin Infect Dis. 2013 Feb; 26(1):50-7
5Thompson 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
6World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 21/10/13]
7Centers 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 21/10/13]
8World Health Organisation. Hepatitis C Fact Sheet. Updated July 2012 http://www.who.int/mediacentre/factsheets/fs164/en/index.html [Last accessed on 21/10/13]
9Chen 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 21/10/13]
10Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009
* Faldaprevir and deleobuvir are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.
^SVR12 = sustained viral response 12 weeks after treatment completion, also described as “viral cure”
SOURCE: Boehringer Ingelheim
