TreatmentUpdate
215

May/June 2016 

ABT-493 + ABT-530 in genotype 3 with cirrhosis

The strain of HCV called genotype 3 has been difficult to cure with direct-acting antivirals (DAAs). Furthermore, research suggests that genotype 3 is associated with the following:

  • an increased risk for developing fatty liver
  • a faster rate of scarring within the liver
  • a heightened risk for developing liver cancer

Researchers in the United States and New Zealand tested the combination of ABT-493 and ABT-530 taken once daily with and without the broad-spectrum antiviral agent ribavirin in participants with cirrhosis for 12 weeks. None of the participants had previously used treatment. The combination resulted in very high rates of cure (100%) when used for 12 consecutive weeks, with or without ribavirin.

Study details

In a series of phase II clinical trials called Surveyor-2 part 2, researchers tested ABT-493 and ABT-530. The average profile of participants with genotype 3 upon entering the study was as follows:

  • age – 56 years
  • 65% men, 35% women
  • body mass index (BMI, a relative indicator of fatness) – 27
  • 96% of participants had genotype 3a
  • all participants had cirrhosis (severe scarring of the liver) but none had symptoms of this condition. Seventeen percent had cirrhosis graded as Child-Turcotte-Pugh A (CTP-A), which suggested that their chances of survival over the next 12 months were very high. No participant had cirrhosis of a more severe grading.

Participants were randomly assigned to receive the following regimens:

  • ABT-493 (300 mg) + ABT-530 (120 mg) – 24 participants
  • ABT-493 + ABT-530 + ribavirin (800 mg) – 24 participants

All drugs were taken for 12 weeks.

Results

All participants were cured 12 weeks after cessation of study drugs. Thus, adding ribavirin to a regimen of the Abbvie drugs offers no advantage for patients with genotype 3 who have cirrhosis.

Adverse events

Reports of adverse events were distributed among the following proportion of participants:

  • ABT-493 + ABT-530 – 88%
  • ABT-493 + ABT-530 + ribavirin – 83%

Common adverse events were as follows:

Headache

  • ABT-493 + ABT-530 – 13%
  • ABT-493 + ABT-530 + ribavirin – 33%

Fatigue

  • ABT-493 + ABT-530 – 8%
  • ABT-493 + ABT-530 + ribavirin – 25%

Nausea

  • ABT-493 + ABT-530 – 8%
  • ABT-493 + ABT-530 + ribavirin – 25%

Dizziness

  • ABT-493 + ABT-530 – 8%
  • ABT-493 + ABT-530 + ribavirin – 17%

Diarrhea

  • ABT-493 + ABT-530 – 21%
  • ABT-493 + ABT-530 + ribavirin – 0%

Note that in other studies of the Abbvie drugs diarrhea was uncommon.

Serious adverse events were distributed as follows:

ABT-493 + ABT-530 – one person

One person taking this regimen developed a fracture in one of his/her leg bones 15 days after the cessation of treatment. Bear in mind that HCV infection has been associated with reduced bone density. Investigators determined that this person’s problem was not linked to the study drug.

ABT-493 + ABT-530 + ribavirin—two people

One month after starting this regimen, one person developed lower-than-normal levels of the iron-containing protein hemoglobin. This condition is called anemia. Investigators determined that this was possibly related to the use of ribavirin.

Another person developed delusions three days after treatment cessation. Investigators thought that this issue could have been related to the study medications. However, the person also disclosed the use of amphetamine and alcohol the same day, which may also have played a role.

Abnormal laboratory test results

No participant had moderate or greater elevations of liver enzyme levels in their blood.

Users of the ABT drugs without ribavirin very rarely had elevated levels of the waste product bilirubin in their blood. In contrast, about 30% of participants who took the ABT drugs plus ribavirin had elevated levels.

Resistance

The proportion of participants with strains of HCV that could resist the study drugs was between 33% and 42% (depending on the resistance mutation assessed). Despite having these mutations, participants were cured.

Key points

Twelve consecutive weeks of therapy with ABT-493 + ABT-530 was able to cure 100% of participants with genotype 3 and cirrhosis whether or not ribavirin was used. Furthermore, participants were cured despite the presence of strains of HCV that could confer resistance. Therapy was generally well tolerated.

—Sean R. Hosein

REFERENCE:

Kwo PY, Wyles DL, Wang S, et al. 100% SVR12 with ABT-493 and ABT-530 with or without ribavirin in treatment-naïve genotype 3-infected patients with cirrhosis. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract LB01.