Abbott and Enanta Pharmaceuticals announced 12-week results from a phase II study of ABT-450/r, an investigational, oral protease inhibitor being developed for the treatment of Hepatitis C (HCV) infection. Study results show that 92 per cent (22 of 24) of patients taking ABT-450/r once daily, combined with standard of care, achieved complete early virologic response (HCV RNA levels <25 IU/mL) at 12 weeks. Results were presented at the European Association for the Study of Liver Disease (EASL) annual meeting in Berlin.
Some of the findings during the 12 week study has 92 per cent of patients receiving ABT-450/r (ABT-450 with 100 mg of ritonavir to support once-daily dosing) in combination with Standard Of Care (SOC) – pegylated interferon alpha and ribavirin (pegIFN/RBV) – achieved HCV-RNA <25 IU/mL. In a separate analysis of 3-day resistance data, ABT-450/r dosed at 200/100 mg appeared to more consistently suppress the emergence of ABT-450-associated resistant variants than the 50/100 mg and 100/100 mg doses. Previously presented 3-day and 4-week results from the study had suggested the ABT-450/r demonstrated significant antiviral activity in treatment-naïve adults. After three days, treatment with ABT-450/r alone resulted in 4-log (10,000-fold) mean reductions of HCV RNA, across the three dose ranges of ABT-450 (50 mg, 100 mg, 200 mg, once-daily dosing)
“A significant number of HCV patients are unable to begin treatment with peginterferon and ribavirin, and for those that do begin treatment, more than 50 percent will not be cured,” said Fred Poordad, MD, chief of hepatology at the Liver Disease and Transplant Centre at Cedars-Sinai Medical Centre in Los Angeles, and one of the investigators for the study. “These results suggest that ABT-450/r could be an important component in combination therapy approaches to treating HCV.”
“Abbott is working to transform treatment options for patients with HCV infection by investigating ways to simplify treatment and increase cure rates,” said Scott Brun, MD, divisional vice president, infectious disease development, Abbott. “We will continue to explore the use of ABT-450/r and our other investigational HCV treatments in a variety of patient populations and combinations, with and without pegylated interferon alpha.”
“We continue to be encouraged by the results for ABT-450/r and the potential it holds for treatment-experienced and treatment-naive patients with HCV,” said Jay Luly, PhD, president and chief executive officer, Enanta Pharmaceuticals.
The objectives of the 48-week phase II study are to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple dose strengths of ABT-450/r in treatment-naïve adults infected with HCV genotype 1, which is the most common and difficult to treat form of the infection in the developed world. Trial endpoints include early virologic response and rapid virologic response. Initial antiviral activity was evaluated via a 3-day treatment period during which ABT-450/r was administered alone. Subsequently, ABT-450/r was administered with pegIFN/RBV (SOC) for 12 weeks, followed by treatment with SOC alone for an additional 36 weeks. Participants are then monitored post therapy for 24 weeks for sustained virologic response.
In the trial, the most common adverse events reported in subjects receiving ABT-450/r in combination with pegIFN/RBV were headache, fatigue, insomnia and depression. A similar proportion of subjects reported at least one adverse event in all treatment groups, including placebo.
ABT-450 is being developed with low-dose ritonavir, which enhances the pharmacokinetic properties of ABT-450, allowing for once-daily dosing. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.
Hepatitis C is a liver disease affecting more than 180 million people worldwide. The virus is primarily spread through direct contact with the blood of an infected person. HCV increases a person's risk of developing chronic liver disease, cirrhosis, liver cancer and death.
Liver disease associated with HCV infection is growing rapidly, and current therapies only cure about half of patients with the genotype 1 form of the virus. Specifically targeted antiviral therapies for HCV, such as protease inhibitors and non-nucleoside polymerase inhibitors, may have the potential to increase the proportion of patients in whom the virus can be eradicated.
Ritonavir is in a class of medicines called the HIV protease inhibitors. It is used in combination with other anti-HIV medicines to treat people with Human Immunodeficiency Virus (HIV) infection. Ritonavir is for adults and for children greater than 1 month in age and older. It does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. While taking ritonavir people may get opportunistic infections or other conditions that happen with HIV infection. Some of these conditions are pneumonia, herpes virus infections, and Mycobacterium Avium Complex (MAC) infections.
Patients should not take ritonavir with certain medicines, as these can cause serious or life-threatening problems such as irregular heartbeat, breathing difficulties, or excessive sleepiness or if they has a serious allergic reaction to any of its ingredients. They may develop liver and pancreas problems, which can cause death. They may also develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with haemophilia, allergic reactions, and/or changes in heart rhythm.
Enanta Pharmaceuticals is a research and development company that uses its novel chemistry approach and drug discovery capabilities to create best in class small molecule drugs in the infectious disease field.
Abbott's HCV development programmes include its partnership with Enanta Pharmaceuticals to discover protease inhibitors, as well as internal programs focused on additional viral targets, including polymerase inhibitors.