Date: 2013-11-02
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 64th Annual Meeting of the American Association for the Study of Liver Diseases
Company: Boehringer Ingelheim (Germany)
Product: combination of faldaprevir, pegylated interferon and ribavirin
Action mechanism:
Disease: hepatitis C
Therapeutic area: Infectious diseases
Country:
Trial
details:
Latest
news: * On June 20, 2014, Boehringer Ingelheim has re-evaluated its strategy in hepatitis C, and as a result the company has decided not to move forward in this therapeutic area. The HCV treatment environment has significantly and rapidly evolved since the submission of the faldaprevir marketing applications to regulatory bodies around the world. There are now several new treatment options available for patients and additional all-oral options are expected to be approved in 2014. This decision was taken as there is no longer an unmet medical need for the faldaprevir interferon-based regimen that was the subject of the application. Boehringer Ingelheim will withdraw all pending marketing applications for faldaprevir worldwide and is discontinuing further development.
* On November 2, 2013, Boehringer Ingelheim has 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),treatment-experienced patients (STARTVerso™3), and HIV co-infected patients (STARTVerso™4) participated in this study programme.
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). 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. Additionally, treatment of difficult-to-cure patients who have relapsed on previous HCV treatment (STARTVerso™3) demonstrated viral cure rates of 70% with faldaprevir. 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.
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:
*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:
*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).
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:
*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:
*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.
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:
*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)
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:
*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.
Boehringer Ingelheim looks forward to presenting pivotal Phase III HCVerso® data for the treatment of HCV as part of an interferon-free regimen in 2014.
