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What is the DUROS® Technology? The DUROS® device is an implantable osmotic mini-pump. Each device contains an appropriate volume of drug product to treat a patient for a predetermined extended duration of time. The DUROS device is activated when subcutaneous tissue fluid passes through the device inlet, expanding the osmotic engine. The osmotic engine drives the piston at a constant rate, delivering consistent drug levels through the device outlet. The DUROS device can be inserted in a subcutaneous space in between the biceps and triceps during a reimbursable in-office procedure, in as little as 5 minutes by a physician or physician’s assistant, and ensures 100% patient adherence to therapy. Delivering drugs via the DUROS technology avoids unwanted peak drug levels often associated with toxicities and sub-therapeutic troughs often associated with suboptimal therapeutic effects. The DUROS device has been an FDA-approved drug delivery technology for a marketed commercial pharmaceutical product since March 2000.
OMEGA DUROS® Device for Hepatitis C
Omega DUROS for the Treatment of Hepatitis C
Intarcia is developing omega interferon for delivery from the DUROS® device to improve the treatment of HCV by offering a more convenient and potentially safer and more efficacious therapy. 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. The omega DUROS device is designed to deliver a continuous and consistent dose of omega interferon, a therapeutic protein, for three months via the implantable DUROS device. Through this unique and proprietary delivery of interferon, Intarcia expects to improve efficacy 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. The Omega DUROS device would eliminate the need for weekly injections, requiring only four in-office insertions over the 48-week course of therapy.
Omega Interferon Background Omega and alpha interferons hold some similarities in that they are both type-1 interferons, binding to the same receptor and their amino acid sequences share 70% homology. However, unlike currently marketed versions of alpha interferon, Intarcia's omega interferon is derived from Chinese hamster ovary (CHO) cells and is fully glycosylated. These aspects lend unique and robust pharmaceutical properties to omega interferon that facilitate long term stability at human body temperature required for delivery via the DUROS device. Omega interferon has been broadly studied 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. Preliminary results from the most recent phase 2 study comparing injectable omega interferon with the combination of omega interferon and ribavirin have been reported. Twelve week early viral response (EVR) results were presented at the Annual Meeting of the American Association for the Study of Liver Diseases in November 2005, and final results, including sustained viral response (SVR) rates have been accepted for presentation at the Annual Meeting of the European Association for the Study of the Liver on April 12, 2007.
Clinical Development
Intarcia has demonstrated the antiviral activity of omega interferon given by injection in one phase 1b and two phase 2 clinical trials, conducted in over 200 HCV-infected patients. The first of the two phase 2 trials enrolled 90 patients. Approximately two-thirds of the patients had genotype-1 HCV, the remaining had genotypes-2 and -3 HCV. This trial demonstrated that even in genotype-1 virus, the most common but difficult to treat form of HCV, omega interferon exhibits potent antiviral properties, producing single agent Early Viral Response (EVR) rates that compare favorably to alpha interferon. The success of this phase 2 trial enabled us to:
In this second phase 2 trial, 102 patients with genotype-1 HCV were randomized on a 2:1 basis to receive 175 µg per week of omega interferon plus ribavirin or 175 µg per week of omega interferon monotherapy. In total, 67 patients received omega plus ribavirin and 35 received omega monotherapy. The addition of ribavirin provided for a statistically significant improvement in EVR rates - 84% for combination therapy as compared to 60% for monotherapy (p value = 0.014). These data demonstrate the synergistic effect of ribavirin with omega interferon at as early as 12 weeks of treatment. The study was completed in December 2006 for all patients with 48 weeks of therapy and 24 weeks of follow-up, and the data on the Sustained Viral Response (SVR) rates will be presented at the Annual Conference of the European Association for the Study of the Liver (EASL) on April 12, 2007. The phase 2 studies of injectable omega have accelerated Omega DUROS development, by establishing synergy between omega interferon and ribavirin and by identifying an appropriate starting dose to evaluate escalating doses of omega interferon with DUROS delivery. In the second quarter of 2007, Intarcia intends to initiate a phase 1b dose escalation study with the Omega DUROS device and ribavirin in 60 to 90 patients with chronic HCV genotype-1 infection who have relapsed after achieving an end of treatment response following a 48-week course of pegylated interferon plus ribavirin. As is commonly required by regulatory agencies and institutional review boards, Intarcia expects to initially evaluate the Omega DUROS device in a treatment-experienced population in phase 1 and then evaluate the Omega DUROS device in a treatment-naïve population in phases 2 and 3. The phase 1b study is being performed to demonstrate the safety, tolerability, pharmacokinetic profile and antiviral effects of two to three doses of omega interferon administered via the DUROS device. The advantages of the Omega DUROS device over pegylated interferon can be summarized as follows:
Based on these advantages and assuming positive continued clinical results, the Omega DUROS device represents a compelling opportunity for the 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.
Hepatitis C The Centers for Disease Control estimates 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 genotypes. There remain many barriers to effective treatment, including:
Type 2 Diabetes: GLP-1 DUROS® / GLP-1 analog DUROS® Device
GLP-1 DUROS Device Intarcia is developing a GLP-1 formulation for the DUROS® device to provide type 2 diabetes patients with long-term steady state dosing of GLP-1 or a GLP-1 analog. GLP-1 and GLP-1 analogs such as Exendin-4 and others have shown clinical efficacy in glycemic control and weight loss, either as single agents or in combination with oral antidiabetic drugs. With the new GLP-1 analogs, the pharmacokinetic limitations which require twice daily injections and side effects such as nausea may limit wider patient adoption. The GLP-1 DUROS device is designed to deliver a continuous and constant dose of GLP-1/GLP-1 analog over an extended period of time, thereby providing therapeutic benefits to the patient but minimizing Cmax related toxicities such as nausea. GLP-1 DUROS Program Status With the human form of GLP-1, Intarcia has developed formulations that demonstrate excellent stability at body temperature for at least six months for a GLP-1 DUROS device. Intarcia is planning to initiate clinical trials of the GLP-1 DUROS device in 2008. Formulation work for other GLP-1 analogs to be delivered from the DUROS device is ongoing.
Type 2 diabetes is the most common form of diabetes, accounting for more than 90% of all cases, affecting approximately 38 million adults worldwide and more than 20.8 million children and adults in the US alone. According to the American Diabetes Association, 1.5 million new cases of diabetes were diagnosed in people aged 20 years or older in the US in 2005. The treatment for type 2 diabetes can be divided into insulin and non-insulin segments. Type 2 diabetes patients are usually treated with oral antidiabetic drugs after diet and exercise have failed and this market (non-insulin) is valued at approximately $9.0 billion annually. Ultimately however, most type 2 diabetics fail on these drugs and need to move to insulin-based treatment which is currently valued at greater than $9.0 billion annually. GLP-1 or a GLP-1 analog could be used in combination with or to replace therapies in both market segments, providing a substantial commercial opportunity.
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