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

AASLD - Boehringer interim data on hepatitis C interferon-free regimen to be presented

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

 By Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc.

Last modified: 2013-10-08T11:12:26Z

Published: Tuesday, Oct. 8, 2013 - 4:10 am

yright 2013 . All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

RIDGEFIELD, Conn., Oct. 8, 2013 -- /PRNewswire/ -- 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.

Contact:  Boehringer Ingelheim Pharmaceuticals, Inc. 

 Name: Susanne Granold  Public Relations  Phone: 203-791-5851  Email: Susanne.Granold@boehringer-ingelheim.com

SOURCE Boehringer Ingelheim Pharmaceuticals, Inc.

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Hepatitis C - Presidio Collaboration with Boehringer Ingelheim for interferon-free Phase IIa clinical trial

Presidio Pharmaceuticals Announces Collaboration with Boehringer Ingelheim

The Parties to Initiate a Phase IIa Trial of an All-Oral Combination of Presidio's HCV NS5A inhibitor (PPI-668) with Faldaprevir (BI201335) and BI207127 for the Treatment of Patients with Hepatitis C

SAN FRANCISCO--(BUSINESS WIRE)--Mar 13, 2013 - Presidio Pharmaceuticals, Inc. announced today a non-exclusive collaboration with Boehringer Ingelheim for a Phase IIa clinical trial of an interferon-free, all-oral, direct-acting antiviral (DAA) combination treatment for patients with chronic hepatitis C virus (HCV) infection. The collaborative trial will evaluate Presidio's pan-genotypic HCV NS5A inhibitor (PPI-668) in combination with Boehringer Ingelheim's HCV protease inhibitor faldaprevir (BI201335) and its non-nucleoside HCV polymerase inhibitor (BI207127), with or without ribavirin.

Both companies have agreed to initiate the Phase II, 12-week treatment study in the second quarter of 2013. The trial will measure on-treatment antiviral responses and sustained virologic response rates (SVR) to the triple DAA combination regimen, with or without ribavirin. Presidio Pharmaceuticals will have primary operational responsibility for the trial, in close collaboration with Boehringer Ingelheim.

“With the potent, complementary antiviral activities of PPI-668, faldaprevir, and BI207127, the present study focuses on patients with HCV genotype-1a infection, which has been harder to treat than HCV genotype-1b in many studies. The study will assess the potential of this three-drug oral regimen to achieve high rates of sustained viral clearance in hepatitis C patients, with good tolerance,” said Dr. Nathaniel Brown, Presidio's Chief Medical Officer.

Sustained virologic response results at 4- and 12-weeks post-treatment are expected to be available in the fourth quarter of 2013. Both companies continue to retain all rights to their respective compounds during this collaboration.

About Hepatitis C

Chronic hepatitis C is a progressive inflammatory liver disease caused by chronic infection with the hepatitis C virus (HCV). Approximately 170 to 200 million persons have chronic HCV infection worldwide, resulting in more than 350,000 deaths annually.

The current standard treatment for patients with hepatitis C genotype-1 infection in the United States and several other countries is combined administration of pegylated interferon-alfa, ribavirin, and an HCV protease inhibitor.

Due to the efficacy limitations and tolerance issues for interferon-based therapies and the continuing progression of underlying liver damage in the current large population of hepatitis C patients, there is a continuing need for more effective, better-tolerated, interferon-free combination therapies for HCV infection that can be orally administered with convenient, relatively short dosing schedules.

About PPI-668

PPI-668 is a potent, 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. 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.

About faldaprevir (BI201335)

Faldaprevir is an oral once-daily protease inhibitor, specifically designed to target and inhibit viral replication in the liver. Interferon-based therapy with faldaprevir is studied in a broad spectrum of genotype-1 patients. The STARTVerso™ trial program, which includes treatment-naïve, treatment-experienced and HIV co-infected patients, is nearly complete.

About BI207127

BI207127 is an investigational, potent twice-daily non-nucleoside inhibitor of the HCV polymerase (NS5B) that inhibits HCV genotype-1 replication. BI207127 in combination with faldaprevir and ribavirin is currently in Phase III clinical trials (HCVerso 1 and 2).

About Presidio

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical stage specialty pharmaceutical company focused on the discovery and development of novel oral antiviral therapeutics. For more information, please visit our website at: www.presidiopharma.com


Contact: Presidio Pharmaceuticals, Inc.
Leo Redmond, 415-655-7560
lredmond@presidiopharma.com