Boehringer Ingelheim’s interferon-free hepatitis C treatment portfolio strengthened by promising interim Phase 2a data

Clinical trial studies an all-oral, 12-week regimen containing the investigational compounds faldaprevir, deleobuvir, and Presidio Pharmaceuticals’ PPI-668 with and without ribavirin in 36 difficult-to-treat genotype-1a HCV patients

All 13 patients who reached the 4-week post-treatment follow-up had undetectable hepatitis C virus (SVR 4)

For U.S. Media Only

Ridgefield, CT, November 2, 2013– Boehringer Ingelheim Pharmaceuticals, Inc. today announced interim data from its Phase 2a hepatitis C (HCV) clinical collaboration (NCT01859962) with Presidio Pharmaceuticals, Inc. that showed all patients (13/13) who reached the 4-week post-treatment follow-up had undetectable levels of hepatitis C virus (SVR4) with an investigational, 12-week, all-oral regimen of faldaprevir and deleobuvir, in combination with Presidio’s pan-genotypic NS5A inhibitor, PPI-668, with ribavirin. The primary efficacy endpoint of this ongoing trial is sustained virologic response 12 weeks after completion of treatment (SVR12).

An additional study arm evaluating the regimen without ribavirin, which was added per protocol following initial results in the ribavirin-containing arms, showed that after four weeks on treatment, 12/12 patients had hepatitis C virus levels below an amount that can be quantified (LLOQ).  

These data are being presented during the late-breaking poster session at the 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, D.C.

“We continue to be encouraged by the preliminary results of this investigational triple combination of direct-acting antivirals in patients with genotype-1a HCV, and in particular that, at this stage, the ribavirin-free combination has yielded similar results to the ribavirin-containing arms of the trial,” said Jacob Lalezari, M.D., director of Quest Clinical Research in San Francisco, CA.

This ongoing Phase 2a study evaluates 36 treatment-naïve genotype-1a HCV patients. Two thirds of 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, more than half the patients in the study (20/36) have pre-existing HCV mutations. These include the Q80K variant in 12 of these patients, all of which had virologic responses to the faldaprevir-based triple direct-acting antiviral (DAA) regimen. Also in this trial, 19% of patients are African American.

“These results add to the growing body of data for HCV regimens containing our investigational compound, faldaprevir,” said Peter Piliero, M.D., vice president, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. “We are looking forward to the final results of this trial, as well as our other studies evaluating all-oral regimens, as researchers strive to make an interferon-free future a reality for a broad range of HCV patients.”

This study contains three arms:

  • 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 QD, PPI-668 200mg QD and deleobuvir 600mg BID without ribavirin

All patients in the study have received at least 4 weeks of treatment and 97% (35/36) achieved LLOQ. To date, one patient 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.

To date, there has been one treatment discontinuation due to adverse events. The patient self-discontinued at week 9 on treatment due to gastrointestinal side effects. This patient had undetectable levels of HCV RNA by day 10 of treatment. Overall, adverse events 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. Benign bilirubin elevation (unconjugated hyperbilirubinemia) has been common in the trial and has occurred in 88% of patients in ribavirin-containing arms, and 46% of patients in the ribavirin-free arm. In the ribavirin-free treatment arm, most adverse events (83%) have been characterized as mild. In the ribavirin-containing arms, adverse events have been mild to moderate.

In March 2013, Boehringer Ingelheim and Presidio Pharmaceuticals entered into 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. Final results are expected in Q2 2014.

Additional Boehringer Ingelheim Interferon-Free Data
Also at AASLD, data from Boehringer Ingelheim’s interferon-free Phase 2 clinical trial, SOUND-C3 (NCT01132313), are being presented. This study evaluated the investigational compounds, faldaprevir and deleobuvir, with ribavirin in treatment-naïve patients with genotype-1b HCV. The results of this study showed that 95% of patients achieved SVR12 after 16 weeks of treatment.

The SOUND-C3 trial was one of Boehringer Ingelheim’s first studies evaluating investigational faldaprevir without interferon, in combination with investigational deleobuvir and ribavirin. This study informed the company’s current interferon-free development program, including the ongoing clinical collaboration with Presidio Pharmaceuticals.

As part of Boehringer Ingelheim’s long-term commitment to an interferon-free future for patients with HCV, the company recently completed patient enrollment for its Phase 3 clinical trials, HCVerso®1 and 2 (NCT01732796, NCT01728324), which investigate the efficacy and safety of the investigational compounds, faldaprevir and deleobuvir, in combination with ribavirin. These trials evaluate genotype-1b HCV patients, including difficult-to-treat populations such as those who are ineligible for interferon and those with liver disease including cirrhosis. 

Faldaprevir, deleobuvir, and PPI-668 are investigational compounds and not approved. Their safety and efficacy have not 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 (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™ is a multi-study Phase 3 trial program that evaluates faldaprevir combined with PegIFN/RBV. The four trials that make up this program study the combination in treatment-naïve, treatment-experienced and HIV/HCV coinfected patients with chronic genotype-1 HCV. Deleobuvir (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 registered service marks of Boehringer Ingelheim International GmbH.

Hepatitis C is a blood-borne 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, approximately 3.2-5.2 million people 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 endeavors.

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 www.presidiopharma.com.

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