Date: 2013-11-02
Type of information: Presentation of results at a congress
phase: 2
Announcement: presentation of interim data at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), in Washington
Company: Boehringer Ingelheim (Germany) Presidio Pharmaceuticals (USA)
Product: combination of faldaprevir, deleobuvir and PPI-668
Action
mechanism: Faldaprevir is a once-daily protease inhibitor.
Deleobuvir is a non-nucleoside polymerase inhibitor.
PPI-668 is a pan-genotypic HCV NS5A inhibitor.
Disease: hepatitis C
Therapeutic area: Infectious diseases
Country:
Trial
details: The trial includes 36 treatment-naïve patients with genotype-1a HCV treated for 12 weeks with an all-oral regimen, with 24 weeks of post-treatment follow-up. The primary endpoint is viral cure 12 weeks after treatment completion (SVR12). There are three cohorts in this study:
Cohort 1: faldaprevir* 120 mg once-daily (QD), PPI-668 200mg QD and deleobuvir* 600mg twice-daily (BID) with ribavirin (n=12)
Cohort 2: faldaprevir* 120 mg QD, PPI-668 200mg QD and deleobuvir* 400mg BID with ribavirin (n=12)
Cohort 3: faldaprevir* 120mg QD, PPI-668 200mg QD and deleobuvir* 600 mg BID, without ribavirin (n=12)
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, interim data from Boehringer Ingelheim’s ongoing Phase II collaborative trial with Presidio Pharmaceuticals have been presented at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington. The data show that all patients (13/13) who reached their 4-week post-treatment follow-up have undetectable levels of hepatitis C virus (SVR4) after completing a 12-week regimen of faldaprevir*, deleobuvir*, PPI-668* and ribavirin. Additional data from the trial show 100% of patients (12/12) treated with a ribavirin-free regimen had hepatitis C virus (HCV) levels below the lower level of quantification at 4 weeks. Safety and tolerability appears to be better in this ribavirin-free treatment arm compared to those with ribavirin.
The ongoing Phase II trial features the 12-week regimen both with and without ribavirin in 36 genotype-1a infected patients, one of the more difficult-to-cure types of hepatitis C virus. In addition, more than half the patients in the study (20/36) had pre-existing HCV mutations. This includes the Q80K variant which is common in genotype-1a infected patients2 and has been associated with reduced responses to some HCV protease inhibitors. Notably, all 12 patients in the study with pre-existing Q80K mutations are responding well to treatment with the faldaprevir*-based interferon-free regimen.
Thirty-six patients in this study have reached week 4 of treatment, 17 patients have reached the end of treatment (12 weeks) and 13 patients have reached their 4 week post-treatment follow-up. Interim results show:
-97% of patients (35/36) achieved HCV levels below the lower limit of quantification at week 4
-100% of patients (17/17) that completed the full course of treatment had undetectable hepatitis C virus at the conclusion of treatment
-100% of patients (13/13) that completed the full course of treatment achieved SVR4
To date there has been just one treatment failure due to viral breakthrough. One patient had an initial virologic response but then exhibited viral breakthrough and was discontinued after 5 weeks of treatment. Only one AE was rated as ‘severe’ and attributable to study drugs; one patient reported severe fatigue in week 11 and the event was resolved with no change in treatment. Overall, adverse events in the study have been mild to moderate, with the incidence and severity of skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir* and deleobuvir*.Pivotal HCVerso® studies which investigate the interferon-free regimen of faldaprevir, deleobuvir and ribavirin are also in Phase III development. Boehringer Ingelheim looks forward to the final results from both trials in Q2 2014.
