AASLD- Abbott hepatitis C oral drugs bring high cure rates in trial

11:34 a.m. CST, November 10, 2012

(Reuters) - A trio of oral medicines from Abbott Laboratories Inc to treat hepatitis C produced unprecedented cure rates in patients who had failed to benefit from standard treatment, as well as very high cure rates for newly treated patients, Abbott said on Saturday.

Detailed data from the mid-stage trial, called Aviator, were released Saturday at the annual meeting of the American Association for the Study of Liver Disease (AASLD) in Boston.

Investors and patients have very high hopes for the Abbott drugs - a protease inhibitor called ABT-450, a polymerase inhibitor ABT-333 and ABT-267 from a class known as NS5A inhibitors. They are used without interferon, an injectable standard treatment that causes flu-like symptoms.

Abbott said it plans to move ahead with large Phase III studies of the three drugs, used either with or without the standard antiviral pill ribavirin, based on favorable results seen in patients treated for eight weeks or twelve weeks in the Aviator study. Patients in the study had the most common, and hardest-to-treat, strain of hepatitis C known as Genotype 1.

Some 93 percent of patients who failed prior therapy had a sustained virologic response (SVR), meaning they were considered cured, after 12 weeks of taking the trio of new drugs, plus ribavirin.

"Nobody anywhere has broken the 50 percent mark in (cure rates) for this population," Scott Brun, a senior Abbott research executive said in an interview. "These are robust results."

Abbott said it aims to be the first company to market an interferon-free regimen to patients with Genotype 1 infections.

Four of 448 patients in the study discontinued treatment due to adverse events, a dropout rate that Abbott said suggested the medicines were very well tolerated.

About 97 percent of previously untreated patients were considered cured after 12 weeks of treatment with the three Abbott drugs, plus ribavirin. Moreover, similarly impressive cure rates were seen among patients taking the three drugs, plus ribavirin, for 8 weeks.

Without ribavirin, 87 percent of previously untreated patients were considered cured after 12 weeks on Abbott's three drugs, Abbott said.

Rival drugmaker Gilead Sciences Inc stole a bit of Abbott's thunder on Saturday by releasing data showing a 100 percent cure rate among previously untreated genotype 1 patients who took only two of its oral treatments, plus ribavirin, for 12 weeks.

A pair of new hepatitis C drugs approved last year, Vertex Pharmaceuticals Inc's Incivek and Merck & Co's Victrelis, significantly boosted cure rates and cut treatment duration to as low as 24 weeks for some patients. But the protease inhibitors must still be taken with interferon, an injected drug that often causes severe flu-like symptoms that lead many hepatitis patients to delay or discontinue treatment.

Gilead, Bristol-Myers Squibb Co and Vertex are racing to develop interferon-free treatment regimens. They are expected to become blockbuster products, if approved, because of their far shorter treatment times and better cure rates, compared with existing drug regimens.

Many analysts view Gilead as current leader both on timing and perceived advantages of its experimental hepatitis C program.

An estimated 3 million Americans are believed infected with the virus, which quietly damages the liver over years or decades and is the biggest reason for liver transplants in the United States. Abbott said as many as 170 million people worldwide are infected.

(Reporting by Ransdell Pierson; Editing by Vicki Allen and Jackie Frank)

Abbott Press Release

Abbott Presents Promising Phase 2b Interferon-free Hepatitis C Results at 2012 Liver Meeting®

  • Investigational Triple-DAA Regimen plus Ribavirin Treatment for 12 Weeks Demonstrated High SVR12 Rates in Intent-to-Treat Analysis
  • Phase 3 Registrational Program Currently Enrolling

November 10, 2012
Abbott Park, Illinois (NYSE: ABT) — Results from Abbott’s phase 2b clinical trial, "Aviator," demonstrated high sustained viral response rates at 12 weeks post-treatment (SVR12) in all 8- and 12-week arms, with combinations of direct acting antivirals (DAAs) given with and without ribavirin (RBV). Results will be presented at the President's Press Conference and the latebreaking clinical trials session at the Liver Meeting, the Annual Meeting of the American Association for the Study of Liver Disease (AASLD) in Boston.

Based on promising results from Aviator, Abbott has selected triple-DAA regimens, with and without ribavirin, to move forward into phase 3 clinical trials. Topline intent-to-treat results for the 12-week, triple-DAA regimen with ribavirin are as follows:

SVR12 in treatment-naïve genotype 1 (GT1) patients was 97.5 percent (77 of 79), and 93.3 percent (42 of 45) in GT1 null responder patients

In GT1a patients, SVR12 was achieved in 96 percent (52 of 54) of treatment naïve patients and 89 percent (25 of 28) of null responder patients

In GT1b patients, SVR12 was achieved in 100 percent of treatment naïve (25 of 25) and null responder patients (17 of 17)
In addition, results from the 12-week triple-DAA regimen without RBV in treatment naïve patients showed:

SVR12 was achieved in 87.3 percent (69 of 79) of GT1 patients
SVR12 in GT1a patients was 83 percent (43 of 52)
SVR12 in GT1b patients was 96 percent (24 of 25)
"Based on the high SVR12 results with Abbott’s triple-direct acting antiviral regimen in GT1 patients, it appears we are moving closer to potential oral treatment regimens that do not require interferon to treat HCV," said Kris Kowdley, M.D., director of the Liver Center of Excellence in the Digestive Disease Institute at Virginia Mason Medical Center, and Clinical Professor of Medicine at the University of Washington in Seattle. "This is encouraging news for the many patients who are unable or unwilling to take interferon."

About Study M11-652 (Aviator)
This phase 2b study assesses the safety, and efficacy of ABT-450/r (dosed 100/100mg to 200/100mg QD), ABT-267 (25mg QD), ABT-333 (400mg BID) and ribavirin in non-cirrhotic treatment-naïve patients and prior peg-interferon/ribavirin null responders for 8, 12 or 24 weeks. Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based. Results from the treatment groups are summarized in the chart below.

Treatment-NaïveNull Responders
Duration8 weeks12 weeks12 weeks
RegimenABT-450/r
ABT-267
ABT-333
RBV
ABT-450/r

ABT-333
RBV
ABT-450/r
ABT-267

RBV
ABT-450/r
ABT-267
ABT-333
ABT-450/r
ABT-267
ABT-333
RBV
ABT-450/r
ABT-267

RBV
ABT-450/r
ABT-267
ABT-333
RBV
Number dosed80417979794545
Relapses9455150
Breakthroughs0111003
Lost to Follow up (LTFU) or withdrew consent1124100
SVR12 (ITT)187.5%
(70/80)
85.4% (35/41)89.9% (71/79)87.3% (69/79)97.5% (77/79)88.9% (40/45)93.3% (42/45)
SVR12 (OD)288.6% (70/79)87.5% (35/40)92.2% (71/77)92% (69/75)98.7% (77/78)88.9% (40/45)93.3% (42/45)
SVR12 (ITT) GT1a84%
(47/56)
79%
(23/29)
85%
(44/52)
83%
(43/52)
96%
(52/54)
81%
(21/26)
89%
(25/28)
SVR12 (ITT) GT1b96%
(23/24)
100%
(12/12)
100%
(27/27)
96%
(24/25)
100%
(25/25)
100%
(18/18)
100%
(17/17)

ITT (Intent-to-treat) population: includes all patients who received at least one dose of study drug

OD (Observed data): Excludes patients with values missing for reasons other than virologic failure or discontinuation due to AEs
"The 93.3 percent SVR12 seen with triple-DAA therapy with ribavirin in previous null responder patients in Aviator is noteworthy given the limited treatment options with interferon-based therapies for this patient population," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "As the data from the Aviator study have matured, we are encouraged that we have continued to see high SVR12 rates. Results from Aviator have allowed Abbott to confidently move into larger, confirmatory Phase 3 trials with the goal of being the first company to bring an interferon-free treatment regimen to genotype 1 patients."

Aviator Safety Results
Four of 448 patients (one percent) in the 8- and 12-week arms discontinued due to adverse events. Of five serious AEs (1 percent), one (arthralgia or joint pain) was possibly study drug-related. In the trial, the most common adverse events were fatigue (28 and 27 percent) and headache (28 and 31 percent) for treatment naïve and null responders respectively.

About the Hepatitis C Virus
Hepatitis C is a liver disease affecting as many as 170 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; and liver disease associated with HCV infection is growing rapidly.
Of the six main genotypes of hepatitis C, genotypes 1, 2 and 3 are the most widespread. Genotype 1 is the most common genotype in the U.S. and the most difficult to treat with interferon based therapies. Patients with genotypes 2 and 3 are more likely than individuals with genotype 1 to respond to therapy with peg-interferon or the combination of peg-interferon and ribavirin.

About Abbott's HCV Development Programs
Abbott'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 Abbott and Enanta Pharmaceuticals for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by Abbott for use in combination with Abbott's other investigational medicines for the treatment of HCV. Abbott is well-positioned to explore combinations and co-formulations of these medicines.

On Monday, November 12 at 5:30 p.m. EST, Abbott will host an investor webcast to discuss the phase 2b Aviator data, as well as our recently initiated phase 3 registrational program. The webcast can be accessed on Abbott’s investor relations website at abbottinvestor.com.

Ritonavir Use in 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 Abbott
Abbott (NYSE: ABT) is a global, broad-based health care company devoted to the discovery, development, manufacturing and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries.

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