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

02 November 2013
Phase III data show Boehringer Ingelheim's faldaprevir* was highly effective in a broad range of patients with genotype-1 hepatitis C

• 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

For media outside of the U.S.A., UK and Canada only

INGELHEIM, 2 November, 2013 – 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% (140/185^a)
• 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

 

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