Value through InnovationOctober 22 2014
October 08, 2013

Investigational interferon-free regimen demonstrates undetectable hepatitis C virus in all patients reaching end of treatment in ongoing Phase 2 trial

Collaborative trial from Boehringer Ingelheim and Presidio Pharmaceuticals investigates triple-DAA regimen of faldaprevir, deleobuvir and PPI-668

Trial enrolled 36 hard-to-treat genotype-1a patients; majority have non-CC IL28B genotype and a proportion have pre-existing resistance-associated HCV mutations

Of the patients who have completed 4 weeks of treatment, 97 percent (28/29) achieved rapid virologic response, and 100 percent of patients (13/13) who have completed all 12 weeks of the investigational regimen had undetectable levels of hepatitis C virus at the end of treatment

Ridgefield, CT, October 8, 2013 Boehringer Ingelheim Pharmaceuticals, Inc. today announced that interim data from its Phase 2 hepatitis C (HCV) clinical collaboration (NCT01859962) with Presidio Pharmaceuticals have been accepted as a late breaker poster presentation at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), also known as The Liver Meeting®, taking place November 1-5 in Washington, D.C. The poster presentation will be on Monday, November 4.

This ongoing study evaluates a 12-week, all-oral regimen of Boehringer Ingelheim’s investigational compounds, the protease inhibitor, faldaprevir (BI 201335), and non-nucleoside NS5B polymerase inhibitor, deleobuvir (BI 207127), in combination with Presidio’s investigational pan-genotypic NS5A inhibitor, PPI-668, with and without ribavirin. The study is fully enrolled (36 patients) and to date, 97 percent of patients (28/29) have achieved undetectable levels of virus by week 4 on treatment, also known as rapid virologic response (RVR). Additionally, 100 percent of patients who have completed treatment (13/13) achieved non-detectable levels of virus at the end of treatment. 

“These results are promising particularly because they show the potential to evaluate harder-to-treat populations; all patients studied were genotype-1a and the majority of patients had the non-CC IL28B genotype,” said Jacob Lalezari, M.D., director of Quest Clinical Research in San Francisco, CA.

Two thirds of study patients have the difficult-to-treat CT or TT IL28B genotype. Previous studies have shown that presence of the CT and TT IL28B genotypes led to a reduced likelihood of achieving viral cure. In addition, of the 29 patients who have completed 4 weeks of treatment, 11 had NS5A and/or NS5B mutations, which can be associated with resistance to HCV treatment. Only one of these patients, who had pre-existing NS5A and NS5B mutations, failed treatment. This patient had a partial response to treatment but developed viral breakthrough and was discontinued.

“This collaboration highlights our long-term commitment to developing interferon-free therapeutic options to fulfill unmet needs for patients with HCV, including those who are difficult to treat,” said Peter Piliero, M.D., vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are encouraged by these data, which further provide support for faldaprevir, the foundation of both our investigational interferon-based and interferon-free HCV regimens.”

To date, there have been no treatment discontinuations for adverse events in this study. Adverse events have been mild to moderate, with skin rashes and gastrointestinal side effects similar to those observed in previous trials studying faldaprevir and deleobuvir.

The trial includes 36 treatment-naïve patients with genotype-1a HCV treated for 12 weeks with an all-oral DAA regimen, with 24 weeks of post-treatment follow-up. There are three arms in this study:

  • The first arm enrolled 12 patients and is evaluating faldaprevir 120 mg once-daily (QD), PPI-668 200mg once-daily (QD) and deleobuvir 600mg twice-daily (BID) with ribavirin
  • The second arm enrolled 12 patients and is evaluating faldaprevir 120 mg QD, PPI-668 200mg QD and deleobuvir 400mg BID with ribavirin
  • The third arm enrolled 12 patients and is evaluating faldaprevir 120 mg once-daily (QD), PPI-668 200mg once-daily (QD) and deleobuvir 600mg twice-daily (BID) without ribavirin

The primary endpoint of the trial is viral cure 12 weeks after treatment completion (SVR12).

In March 2013, Boehringer Ingelheim and Presidio Pharmaceuticals entered a non-exclusive collaboration to evaluate the three DAAs in combination regimens. Both companies will retain all rights to their respective compounds. Presidio has operational responsibility for this collaborative trial, with oversight by an intercompany project team. Post-treatment sustained response data will be presented at AASLD next month, and final results are expected in Q2 2014.

As part of the company’s long-term commitment to developing new therapeutic options for HCV, Boehringer Ingelheim recently completed enrollment for its pivotal Phase III interferon-free HCVerso® 1 and 2 trials (NCT01732796, NCT01728324) evaluating faldaprevir and deleobuvir in combination with ribavirin. Earlier reported data demonstrated high cure rates in hepatitis C patients with genotype 1b infection. This trial also studies difficult-to-treat patients including those who are ineligible for interferon, and those with liver cirrhosis.

Faldaprevir and deleobuvir (BI 207127) are investigational compounds and not yet approved. Their safety and efficacy have not yet been fully established.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)
In partnership with the scientific community, our clinical trial program is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat. Our pivotal HCV clinical trials for faldaprevir and deleobuvir are comprised of two multi-trial programs, STARTVerso™ (NCT01343888, NCT01297270, NCT01358864, NCT01399619) and HCVerso®.

Faldaprevir, also known as BI 201335, is an investigational, oral protease inhibitor that is specifically designed to target viral replication in the liver. Boehringer Ingelheim is developing faldaprevir as a core component of both interferon-based and interferon-free hepatitis C treatment regimens. STARTVerso™1 is the first of an ongoing multi-study Phase 3 trial program that is evaluating faldaprevir combined with PegIFN/RBV. Three additional trials in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV are near clinical completion. Deleobuvir, also known as BI 207127, is an investigational NS5B non-nucleoside polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined in a regimen with faldaprevir and RBV. Phase 2 trials of this interferon-free regimen have been completed and Phase 3 HCVerso® trials investigating this regimen are now underway. As part of our long-term commitment to HCV, the company is exploring other combinations of investigational HCV compounds that work in complementary ways. The recent collaboration of Boehringer Ingelheim with Presidio Pharmaceuticals, Inc. for a Phase 2a clinical study investigating an interferon- and ribavirin-free, all-oral combination is part of the company’s continued commitment to discover and develop innovative options for the treatment of HCV.

STARTVerso™ and HCVerso® are service marks of Boehringer Ingelheim International GmbH.

Hepatitis C is a blood-born infectious disease and a leading cause of chronic liver disease, transplant and failure that affects as many as 150 million people globally. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. Since 1999 there has been a significant increase in deaths due to chronic HCV, which accounts for 10,000 -12,000 deaths in the United States per year.

About Boehringer Ingelheim
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

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 endeavours.

For more information please visit www.us.boehringer-ingelheim.com

About Presidio in Hepatitis C Virus (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 GT3a HCV-infected patients.

Presidio’s NS5B inhibitor, PPI-383, is a novel pan-genotypic non-nucleoside 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

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    Boehringer Ingelheim Pharmaceuticals, Inc.