Results from Abbott’s multiple interferon-free Phase 2 HCV studies to be presented at ILC 2012

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AbbottApr 5 2012

Abbott (NYSE: ABT) will present clinical trial results from two different interferon-free, Phase 2 studies for the treatment of hepatitis C (HCV) at the International Liver Congress™ 2012 (ILC 2012), the annual meeting of the European Association for the Study of the Liver (EASL), April 18-22 in Barcelona, Spain. Abstracts for the meeting were published online today.

In the study known as "Co-Pilot," different doses of ABT-450/r, plus ABT-333 and ribavirin administered for 12 weeks showed sustained virological response at 12 weeks post treatment (SVR12) in 95 percent and 93 percent of treatment-naive genotype 1 (GT1) patients. In these patients, response was independent of HCV subtype, host IL28B genotype or dose of ABT-450/r. In addition, SVR12 was achieved in 47 percent of patients who were previous non-responders to past HCV treatment.

In a separate study, known as "Pilot," 91 percent of genotype 1 infected, treatment-naive patients taking ABT-450/r and ABT-072 combined with ribavirin administered for 12 weeks, achieved sustained viral response at 24 weeks (SVR24).

Full results with longer-term follow-up data from both studies will be presented at the meeting. Abstracts are available at www.easl.eu.

"We are extremely encouraged to see this level of sustained response with only 12 weeks of therapy in patients who were new to treatment, and to see a response in patients who had failed past treatment because options to cure this population are limited," said Fred Poordad, M.D., chief of hepatology at Cedars-Sinai Medical Center in Los Angeles, and the lead investigator for Co-Pilot and an investigator for Pilot. "These data suggest that an interferon-free, all-oral regimen of direct-acting antiviral medications could be an important new treatment option for HCV, and we look forward to presenting additional data at the meeting."

"At this meeting, Abbott will present some of the first sustained viral response data for short course, interferon-free regimens for the treatment of HCV. The data suggest that with a 12-week regimen containing just two of our direct-acting antiviral medicines, and no peginterferon, we can achieve high cure rates in treatment-naive, genotype 1 patients," said Scott Brun, M.D., divisional vice president, Infectious Disease Development, Abbott. "Abbott's HCV pipeline includes several compounds in different drug classes and we have the flexibility to study a variety of multi-drug regimens for HCV, with a focus on interferon-free treatments. Abbott is committed to exploring a wide variety of options in our portfolio with the goal of developing optimized regimens to help patients."

Current treatments for HCV remain interferon-based and a significant number of HCV patients are unable or unwilling to take interferon due to contraindications and/or side effects. 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.

These two studies represent an important part of Abbott's broader HCV development program. Larger Phase 2 clinical trials are ongoing, and Abbott expects to present additional data later this year. In addition to its partnership with Enanta Pharmaceuticals on ABT-450 and protease inhibitors, Abbott has internal programs focused on additional viral targets. Abbott currently has investigational medicines with three different mechanisms of action in its ongoing clinical trials, including protease, polymerase and NS5A inhibitors. Abbott is well-positioned to explore combinations of these compounds, a strategy with the potential to markedly transform current treatment practices by shortening therapy duration, improving tolerability and increasing cure rates.

Study M12-746 (Co-Pilot)

Fred Poordad, et al.; Saturday, April 21, 15:30-17:30 CET / 8:30-10:30 a.m. CDT.

"12-Week Interferon-Free Regimen of ABT-450/r+ABT-333+Ribavirin Achieved SVR12 in More Than 90% of Treatment-Naive HCV Genotype-1-Infected Subjects and 47% of Previous Non-Responders"

The objectives of this Phase 2 study were to assess safety and tolerability of 12-week, interferon-free regimens in HCV GT1 patients who were either treatment-naive or previous non-responders. The trial had three arms with three primary endpoints – rapid virological response (RVR) at week 4 and SVR at weeks 4 and 12.
Enrollment was open to GT1-infected patients regardless of IL28B host genotype and ribavirin dosing was weight-based.
95 percent (18 of 19) of treatment-naive patients infected with HCV GT1
(17 GT 1a, 2 GT 1b) achieved SVR12 with ABT-450/r 250/100 mg dosed once daily (QD) + ABT-333 400 mg dosed twice daily (BID) + ribavirin (Arm 1).
93 percent (13 of 14) of treatment-naive patients infected with HCV GT1
(11 GT 1a, 3 GT 1b) achieved SVR12 with ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 2).
47 percent (8 of 17) of patients with HCV GT1 (16 GT 1a, 1 GT 1b) who had previously not responded to other HCV treatments achieved SVR12 with ABT-450/r 150/100 mg QD + ABT-333 400 mg BID + ribavirin (Arm 3).
One patient in Arm 1 discontinued due to asymptomatic isolated ALT/AST elevations at week 2. One patient in Arm 2 discontinued due to noncompliance in week 1. All remaining patients in Arms 1 and 2 completed treatment and achieved SVR12. In Arm 3, six patients experienced viral breakthrough while on treatment and three patients relapsed after treatment stopped.
In the trial the most common adverse events were fatigue (42 percent), nausea (22 percent) and headache (20 percent).

Study M12-267 (Pilot)

Eric Lawitz et al.; Thursday, April 19, 16:00-18:00 CET / 9:00-11:00 a.m. CDT.

"A 12-Week Interferon-Free Regimen of ABT-450/r, ABT-072, and Ribavirin was Well Tolerated and Achieved Sustained Virologic Response in 91% Treatment-Naive HCV IL28B-CC Genotype-1-Infected Subjects"

The objectives of the 12-week, Phase 2 study were to assess the safety, tolerability, pharmacokinetics and antiviral activity of ABT-450/r 150/100 mg QD and ABT-072 400 mg QD + ribavirin administered for 12 weeks.
The study was conducted in 11 treatment-naive adults with host IL28B "CC" genotype from multiple ethnic backgrounds with non-cirrhotic HCV GT1 (8 GT 1a, 3 GT 1b). Ribavirin 1,000-1,200 mg/day was weight-based and dosed twice daily.
The primary endpoint was percentage of patients with HCV RNA <25 IU/mL from week 4 through 12. Other trial endpoints include early virologic response, RVR and SVR through 24 weeks.
100 percent of patients maintained HCV RNA levels <25 IU/mL from weeks
4 through 12 of treatment, and all had undetectable HCV RNA from week 5 to the end of treatment.
91 percent of patients (10 of 11) achieved SVR24.
In the trial, the most common adverse events reported were headache, fatigue, nausea and dry skin. There were no premature discontinuations.

ABT-450 is being developed with low dose ritonavir (ABT-450/r), which enhances the pharmacokinetic properties of ABT-450. The use of ritonavir 100 mg with ABT-450 for the treatment of HCV is investigational.

In addition to the oral presentations, Abbott has six poster presentations at ILC 2012:

Tami Pilot-Matias et al.; Friday, April 20 (11:00-11:30, 12:30-14:00, 15:30-16:00 CET)
"In vitro combinatory effect of HCV NS3/4A protease inhibitor ABT-450, NS5A inhibitor ABT-267, and non-nucleoside NS5B polymerase inhibitor ABT-333"
Robert W. Baran et al.; Friday, April 20 (11:00-11:30, 12:30-14:00, 15:30-16:00 CET)
"Hepatitis C Virus Patient Reported Outcomes (HCVPRO): Development and Validation of a Disease-Specific Patient Reported Outcomes Instrument for Health-Related Quality of Life Measurement"
Eric Lawitz et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
"Safety and antiviral activity of ABT-267, a novel NS5A inhibitor, during 3-day monotherapy: first study in HCV genotype-1 (GT1)-infected treatment-naive subjects"
J Greg Sullivan et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
"ABT-267 combined with pegylated interferon alpha-2a/ribavirin in genotype 1 (GT1) HCV-infected treatment-naive subjects: 12 week antiviral and safety analysis"
Eric Lawitz et al; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
"ABT-450/ritonavir (ABT-450/r) combined with pegylated interferon alpha-2a/ribavirin after 3-day monotherapy in genotype 1 (GT1) HCV-infected treatment-naive subjects: 12-week sustained virologic response (SVR12) and safety results"
Fred Poordad et al.; Saturday, April 21 (11:00-11:30, 12:30-13:30, 15:00-15:30 CET)
"ABT-072 or ABT-333 combined with pegylated interferon/ribavirin after 3-day monotherapy in HCV genotype 1 (GT1)-infected treatment-naive subjects:
12-week sustained virologic response (SVR12) and safety results"