AASLD-Boehringer Ingelheim's interferon-free hepatitis C treatment portfolio strengthened by promising Phase II data

02 November 2013

Boehringer Ingelheim's interferon-free hepatitis C treatment portfolio strengthened by promising Phase II data

• High rate of virologic response in Phase II hepatitis C trial of a 12 week all-oral combination of Boehringer Ingelheim’s faldaprevir* and deleobuvir* and Presidio’s PPI-668* with and without ribavirin¹
• All patients (17/17) who have completed treatment achieved undetectable levels of hepatitis C virus at the end of treatment¹
• 13 of these patients have reached their 4-week post-treatment follow-up and all have undetectable hepatitis C virus (SVR4)¹

 

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

INGELHEIM, 2 November, 2013 – Interim data presented today 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.¹ These data from Boehringer Ingelheim’s ongoing Phase II collaborative trial with Presidio Pharmaceuticals will be presented on Monday during the ‘Late-Breaking Posters’ session at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, D.C. 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.¹ Safety and tolerability appears to be better in this ribavirin-free treatment arm compared to those with ribavirin.¹

“These interim results add to the growing body of evidence for faldaprevir* as an effective treatment for a broad range of genotype-1 infected hepatitis C patients, including the more difficult-to-cure. The trial is still in the early stages but the initial results look promising,” said Professor Klaus Dugi, Senior Vice President of Medicine at Boehringer Ingelheim. “These data further demonstrate the future potential of faldaprevir* as the foundation of interferon-free treatment regimens. Our pivotal HCVerso^® studies which investigate the interferon-free regimen of faldaprevir*, deleobuvir* and ribavirin are currently in Phase III development. We look forward to the final results from both trials in Q2 next year.”

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.¹

To date, all patients in the study have received at least 4 weeks of treatment and 97% (35/36) achieved HCV levels below the lower limit of quantification at week 4. One patient had an initial virologic response but then exhibited viral breakthrough and was discontinued after 5 weeks of 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*. For further results see notes to editors.

Overview of Boehringer Ingelheim’s HCV trial programme
 

Boehringer Ingelheim’s hepatitis C clinical trial programme includes a broad range of genotype-1 infected patients. The programme features three treatment regimens, with faldaprevir* as the foundation:
 

Study	Regimes	Population	Status
STARTVerso™	Faldaprevir* pegylated interferon, ribavirin	GT-1 , TN, TE, HCV/HIV co-infection, advanced liver disease	Regulatory submissions pending
For results see the STARTVerso press release here
HCVerso®	Faldaprevir*, deleobuvir*, ribavirin	GT-1b, TN, TE, advanced liver disease	Phase III results expected Q2 2014
Presidio collaboration	Faldaprevir*, deleobuvir*, PPI-668* +/- ribavirin	GT-1a, TN, non-cc IL28B	Phase II final results expected Q2 2014

 

An individualised approach to hepatitis C

The breadth of patients studied in Boehringer Ingelheim’s hepatitis C trial programme reflects a population that physicians see in the clinic, including those with difficult types of hepatitis C virus to cure.

“The huge diversity between hepatitis C patients, due to differing personal factors and variations in the virus, highlight the importance of an individualised approach to treatment,” said Graham Foster, Professor of Hepatology, Queen Mary’s, London. “The difference between HCV genotypes is substantial. For example, genotype-1a and 1b share only around 70% of the same genetic material which is more distant than the genetic similarity between humans and some other animals and patients have differing degrees of liver damage that may require changes to the therapeutic approach. Given the diversity of the disease and the virus it is likely that each patient will need to be assessed on an individual basis and the best treatment assigned accordingly.”

For more information on the importance of an individualised approach to hepatitis C, view the video here
 

NOTES TO EDITORS
Phase IIa Presidio collaboration trial results 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:¹

• 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)

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:¹

• 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.¹