Value through Innovation21 April 2014
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

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 64th 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

Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim

Professor Klaus Dugi, Senior Vice President Medicine at Boehringer Ingelheim

“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

Newshome

 

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 STARTVerso™ and HCVerso®
For information on the interferon-free Phase III HCVerso® trials please refer to the Clinical Trials backgrounder, available on NewsHome.

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.4 Chronic hepatitis C is a major public health issue and one of the most prevalent infectious diseases worldwide, affecting around 170 million people, with 3-4 million new cases occurring each year.6

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.7 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.8 Advanced liver disease due to hepatitis C currently represents the main cause for liver transplantation in the western world.8

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.

About Presidio in HCV
Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company focused on the discovery and development of oral pan-genotypic therapeutics for HCV patients.  Efforts are currently focused on novel inhibitors of both the HCV NS5A and NS5B genes. PPI-668 is an investigational, pan-genotypic, once daily, NS5A inhibitor. In earlier clinical studies in healthy volunteers and HCV-infected patients, PPI-668 has been well-tolerated to date with no serious or severe adverse events and no apparent pattern of treatment-related clinical side effects or laboratory abnormalities. PPI-668 achieves plasma concentrations high enough to inhibit most pre-existing resistant variants and achieves steady-state levels after a single dose. In a clinical study of PPI-668 monotherapy in GT1 HCV-infected patients, viral load reductions of 3.5 to 3.7 log10 HCV were achieved in 1-2 days. Activity was also noted in GT3 HCV-infected patients.

Presidio’s NS5B inhibitor, PPI-383, is a novel pan-genotypic non-nucleosidic inhibitor with potential to inhibit all of the major HCV genotypes. This compound is currently in Phase 1 studies in healthy subjects. For more information, please visit our website at: www.presidiopharma.com.

References

1Lalezari, et al. Rapid and Consistent Virologic Responses in a Phase 2 Trial of a New All-Oral Combination of Faldaprevir, Deleobuvir and PPI-668, with and without Ribavirin, in Patients with HCV Genotype-1a 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
2Wyles, D. L. Perspective: Beyond Telaprevir and Boceprevir: Resistance and New Agents for Hepatitis C Virus Infection. Drug Resistance in HCV 2012; 20(4):139-145
3FDA Antiviral Drugs Adviosory Committee Meeting: Background Package for NDA 205123, Simeprevir (TMC435). 2013 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/AntiviralDrugsAdvisoryCommittee/UCM371623.pdf [last accessed 24/10/2013]
4World Health Organisation. Hepatitis C. 2002 http://www.who.int/csr/disease/hepatitis/Hepc.pdf [Last accessed on 21/10/13]5Centers 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]
6World 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]
7Chen 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]
8Soriano, Vincent et al. New Therapies for Hepatitis C Virus Infection. Clinical Infectious Disease, February 2009

 *Faldaprevir, deleobuvir and PPI668 are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.

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