HEPATITIS C

Intarcia is developing interferon for delivery from the DUROS® device to improve the treatment of HCV by offering a therapy with greater activity and improved convenience. The current standard of care for hepatitis C is a combination of pegylated alpha interferon and ribavirin.  Standard therapy fails to induce sustained response in a majority of patients and the 48-week course of weekly injections required for most patients causes frequent and at times severe side effects. Such side effects may discourage patient compliance to therapy leading to dose reduction and at times treatment discontinuation.

DUROS delivery of interferon therapy provides a continuous and consistent dose of interferon for an extended duration via the implantable DUROS device without the need for frequent self-injection. Through this unique and proprietary delivery of interferon, Intarcia expects to improve treatment by maintaining constant human exposure to a therapeutic level of interferon without peaks associated with severe side effects, and troughs associated with sub-therapeutic drug levels and viral breakthrough.

Intarcia has evaluated the class of type 1 interferons for compatibility with the DUROS device.  Several of the assessed type 1 interferon candidates appear to present stability and chemical properties amenable to DUROS delivery.  Intarcia acquired exclusive rights to one of these, omega interferon and has completed formulation development and preclinical testing of Omega DUROS interferon therapy.  Omega interferon has been broadly studied by Intarcia as an injection therapy including phase 1 and 2 clinical studies involving over 200 HCV-infected individuals.  These studies have demonstrated omega interferon’s potent anti-HCV activity and favorable safety profile.

Intarcia has completed a 72-week phase 1b dose ranging clinical study of Omega DUROS interferon therapy (ITCA 638) under a US IND.  The study is evaluating ITCA 638 in combination with ribavirin in 60 patients with genotype 1 HCV infection who had relapsed after achieving an end of treatment response following a 48-week course of pegylated alpha interferon plus ribavirin.  Preliminary results from this study suggest a highly predictable PK/PD profile with steady state drug levels achieved within 24 hours of insertion of ITCA 638 and consistent delivery of desired interferon levels in the blood throughout the first 4 weeks of treatment.  This is further supported by a rapid and profound decrease in HCV RNA within the first days of treatment. 

The advantages of ITCA 638 over pegylated interferon can be summarized as follows:

• Ensures patient compliance to therapy;
• Eliminates the need for frequent self-injections;
• Addresses common aversion to needles (especially among former drug abusers);
• Ameliorates “flu-like symptoms” associated with weekly peak concentrations;
• Reduces opportunity for viral breakthrough resulting from sub-therapeutic troughs; and
• Potential for improved clinical activity compared with pegylated interferon.

Based on these advantages and assuming positive continued clinical results, DUROS interferon therapy represents a compelling opportunity to improve treatment of chronic hepatitis C infection, both as an alternative to pegylated interferon for first-line therapy and as an opportunity to expand the treatable population, including patients who have failed prior pegylated interferon therapy and patients for whom injectable alpha interferon is not appropriate.

 

Chronic Hepatitis C Infection

The Centers for Disease Control estimate there are 3.2 million people in the United States infected with chronic HCV, and the World Health Organization recently increased its estimated global prevalence to over 170 million people. Since the early 1990s, incidence has been reduced in the developed world through screening of blood products. Still, approximately 26,000 new infections occur each year in the US. The current standard of care for HCV is a combination of weekly injections of pegylated alpha interferon and twice daily oral dosing of ribavirin. In clinical studies, sustained viral response (SVR) is achieved in approximately 50% of patients across all HCV genotypes. There remain many barriers to effective treatment, including:

• Genotype 1 virus, accounting for 70% of HCV in US and Europe, is less responsive to treatment (SVR: approximately 40% in clinical studies);
• Side effects cause frequent dose reduction and treatment discontinuation;
• Poor compliance may result in viral breakthrough and treatment failure; and
• Former I.V. drug abusers often can’t tolerate self injections.