AbbVie's Investigational HCV Regimen Receives Breakthrough Therapy Designation from the U.S. Food and Drug Administration

- Interferon-free, direct-acting antiviral combination therapy currently in Phase 3 development

NORTH CHICAGO, Illinois, May 6, 2013 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that its investigational direct-acting antiviral (DAA) combination with and without ribavirin for the treatment of genotype 1 (GT1) hepatitis C virus (HCV) infection has been designated as a Breakthrough Therapy by the U.S. Food and Drug Administration (FDA).

The designation is based, in part, on positive data from AbbVie's clinical development program, including the Phase 2b clinical trial M11-652, known as "Aviator." The Aviator study was conducted in 571 patients infected with HCV GT1. Results from the treatment arms evaluating ABT-450/r + ABT-267 + ABT-333 with and without ribavirin demonstrated that the regimen provided high sustained viral response rates (SVR) with 12 weeks of therapy in patients who had not been previously treated (treatment naive) and in those who had failed prior therapy with pegylated interferon and ribavirin (null responders), regardless of sex, HCV subtype, stage of fibrosis, viral load or IL28B genotype.

According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy designation includes preliminary clinical evidence demonstrating a drug may have substantial improvement on at least one clinically significant endpoint compared to available therapy. A Breakthrough Therapy designation conveys all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.(1)

"AbbVie is pleased that the FDA has granted Breakthrough Therapy designation to our 3-DAA combination with and without ribavirin. We feel it reflects the potential of this regimen to be important in the treatment of HCV," said John M. Leonard, M.D., senior vice president and chief scientific officer, AbbVie. "Our HCV program is one part of our advancing pipeline which is focused on delivering innovative therapies to address pressing areas of unmet clinical need."

New results from Aviator were recently presented at the 2013 International Liver Congress® in Amsterdam. These results continued to demonstrate high SVR rates against GT1 HCV with the 12-week, triple-DAA regimen with ribavirin, across patient types. Specifically,

• 99 percent of treatment-naive patients (n=79) achieved SVR12, 96 percent achieved SVR24 in an intent-to-treat analysis
• 93 percent of prior null responders (n=45) achieved SVR12 and SVR24
• A single relapse with this regimen occurred at post-treatment week two
• Of the 247 patients treated for 12 and 24 weeks with triple DAA with ribavirin, four patients (1.6 percent) discontinued the study because of drug-related adverse events. Serious adverse events were noted in four patients (1.6 percent), with one (arthralgia) considered possibly drug-related. Other events reported in more than 10 percent of patients included headache, fatigue, nausea, insomnia, and diarrhea. Grade 3-4 laboratory abnormalities in total bilirubin (six patients) and ALT (one patient) were noted; all resolved with continued dosing.

AbbVie's all-oral, triple-DAA combination is currently being studied in Phase 3 clinical trials. The Phase 3 program includes more than 2,000 patients with HCV genotype 1, with trial sites in 29 countries. The DAAs in the studies include ABT-450/r (protease inhibitor and ritonavir), ABT-267 (NS5A inhibitor) and ABT-333 (non-nucleoside polymerase inhibitor). Treatment durations under investigation are 12 weeks in non-cirrhotic patients, and 12 or 24 weeks in cirrhotic patients. All patients will be followed for 48 weeks post-treatment. Co-formulated tablets of ABT-450/r and ABT-267 are being used in the Phase 3 trials.

About the Hepatitis C Virus

Across the world, about 160 million people are chronically infected with hepatitis C.(2) Hepatitis C is an inflammation of the liver caused by an infection with the hepatitis C virus (HCV).(3) HCV is transmitted when an infected person's blood enters the bloodstream of another person.(4)

For the hepatitis C virus, there are six major HCV genotypes (GT1-6).(5) Presently, there is no vaccine for the hepatitis C virus (HCV) infection.(5) Decision to treat is dependent on a number of factors such as the amount of liver damage present, other conditions the patient may have, amount of virus in the body, and viral genotype.(5) If treatment is needed, a hepatitis C infection is typically treated with a combination of antivirals.(5)

About AbbVie's HCV Development Programs

AbbVie's HCV portfolio includes investigational medicines with three different mechanisms of action, including protease (ABT-450/r), polymerase (ABT-333) and NS5A (ABT-267) inhibitors, currently being studied in clinical trials. ABT-450 is being developed with low dose ritonavir which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100mg with ABT-450 for the treatment of HCV is investigational.

ABT-450 was discovered during the course of a collaboration between AbbVie and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of HCV. AbbVie is well-positioned to explore combinations and co-formulations of these medicines.

Ritonavir Use in the Treatment of HIV

Ritonavir is in a class of medicines called the HIV protease inhibitors. Ritonavir 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.

Ritonavir does not cure HIV infection or AIDS and does not reduce the risk of passing HIV to others. People taking ritonavir may still 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.

Ritonavir Safety in Treatment of HIV

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. Patients should not take ritonavir if they have had a serious allergic reaction to any of its ingredients. Some patients taking ritonavir may develop liver and pancreas problems, which can cause death.

Patients may develop large increases in triglycerides and cholesterol, diabetes, high blood sugar, changes in body fat, increased bleeding in people with hemophilia, allergic reactions, and/or changes in heart rhythm. Patients may develop signs and symptoms of infections that they already have after starting anti-HIV medicines.

For more information, please see Important Safety Information and Full Prescribing Information.

About AbbVie

AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. In 2013, AbbVie employs approximately 21,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

1. U.S. Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. 2013. http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed April 19, 2013.
2. Lavanchy D. Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect. 2011; 17(2):107-15.
3. World Health Organization. Global Alert and Response (GAR): Hepatitis C. 2003. http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index1.html. Accessed April 9, 2013.
4. World Health Organization. Hepatitis C Fact Sheet 2012. http://www.who.int/mediacentre/factsheets/fs164/en/ Accessed April 9, 2013.
5. European Association for the Study of the Liver. Clinical Practice Guidelines: Management of hepatitis C virus infection. Journal of Hepatology. 2011; 55: 245-264.