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A Novel Triple Combination: ABT-450 + ABT-072 and ABT-333

July 2012

ABT-450 is an HCV protease inhibitor that attacks the HCV protein NS3/4A. This drug must be taken with ritonavir to ensure that levels of ABT-450 remain elevated.

ABT-072 and ABT-333 are non-nucleoside inhibitors (non-nukes) that attack the HCV enzyme NS5B.

In the clinical trial we are about to report on, these three drugs were tested in combination with ribavirin in volunteers who were infected with HCV genotype 1. All participants had either never been previously treated (treatment naive) or, if they had, when they previously received interferon and ribavirin their HCV did not adequately respond to this therapy.

Participants were divided into the following groups and received ribavirin in doses of 1,000 to 1,200 mg daily:

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Group 1 (treatment naive)

  • 11 participants: ABT-450 + ritonavir (150 mg + 100 mg) once daily + ABT-072 (400 mg) once daily + ribavirin

Group 2 (treatment naive)

  • 19 participants: ABT-450 + ritonavir (250 mg + 100 mg) once daily + ABT-333 (400 mg) twice daily + ribavirin

Group 3 (treatment naive)

  • 14 participants: ABT 450 + ritonavir (150 mg + 100 mg) once daily + ABT-333 (400 mg) twice daily + ribavirin

Group 4 (previous non-responders)

  • 17 participants: ABT-450 + ritonavir (150 mg + 100 mg) once daily + ABT-333 (400 mg) twice daily + ribavirin

Experimental treatment was given for 12 consecutive weeks, followed by a period of observation (still ongoing). No participants had severe liver damage or co-infection with HBV or HIV. Their average profile upon entering the study was as follows:

  • 72% men, 28% women
  • age -- 55 years
  • HCV genotypes 1a or 1b present
  • HCV viral load greater than 800,000 IU/ml


Results

The proportion of participants whose viral load was suppressed after 12 weeks was as follows:

  • Group 1: 91%
  • Group 2: 95%
  • Group 3: 93%
  • Group 4: 47%

Two participants were able to suppress HCV but then their virus levels resurged.

No deaths or life-threatening complications occurred.

There were isolated cases of elevated liver enzymes (ALT and AST) in the blood but these were symptom-free and the elevations fell after the end of the study.


Side Effects

Overall, four people developed severe adverse reactions, as follows:

  • elevated bilirubin (this may be due to ABT-450)
  • fatigue
  • pain
  • vomiting

None of these adverse reactions were so severe that participants had to leave the study or temporarily stop taking the drugs.

Rash was uncommon and generally mild when it did occur.

Common side effects were as follows:

  • fatigue
  • nausea
  • headache

Overall, 91% of participants who did not previously receive anti-HCV therapy have had their HCV remain undetectable, while about 47% of previous non-responders were able to achieve an undetectable level of HCV after 12 weeks of therapy.

Both doses of ABT-450 (250 and 150 mg) showed similar efficacy.

Clinical trials with the three ABT drugs are continuing. Researchers plan to assess drug-drug interactions with these and commonly used anti-HIV drugs.


Reference

Cohen D, Poordad F, Lawitz E, et al. 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. In: Program and abstracts of the 8th International Workshop on HIV and Hepatitis Co-infection, 30 May - 1 June 2012, Madrid, Spain.




This article was provided by Canadian AIDS Treatment Information Exchange. It is a part of the publication TreatmentUpdate. Visit CATIE's Web site to find out more about their activities, publications and services.
 

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