Boehringer Ingelheim's Interferon-Free Hepatitis C Treatment Portfolio Strengthened by Promising Interim Phase IIa Data

Boehringer Ingelheim Pharmaceuticals, Inc. has announced interim data from its Phase IIa 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 4 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 atthe 64th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD), taking place in Washington, DC.

"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, MD, director of Quest Clinical Research in San Francisco, CA.

This ongoing Phase IIa study evaluates 36 treatment-naive 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, MD, 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-668 200 mg once-daily (QD) and deleobuvir 600 mg twice-daily (BID) with ribavirin.

     •  The second arm enrolled 12 patients and is evaluating faldaprevir 120 mg QD, PPI-668 200 mg QD and deleobuvir 400 mg BID with ribavirin.

     •  The third arm enrolled 12 patients and is evaluating faldaprevir 120 mg QD, PPI-668 200 mg QD and deleobuvir 600 mg 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 as a result of 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 characterised 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.