TreatmentUpdate
215

May/June 2016 

ABT-493 + ABT-530 – Eight-week treatment in genotypes 1 or 2 without cirrhosis

ABT-493 is the code name for a drug that attacks an HCV enzyme called NS3 and a co-factor of this enzyme called NS4A. It is being tested at a dose of 300 mg once daily.

ABT-530 is the code name for a drug that attacks an HCV protein called NS5A. It is being tested at a dose of 120 mg once daily.

Both drugs are made by Abbvie.

In lab experiments with HCV-infected cells, both of these drugs have powerful anti-HCV activity against all genotypes of HCV (genotypes 1 through 6). In phase II clinical trials, both drugs are taken together once daily and are very promising treatments. A large research program is underway with these drugs and they are in the final phase of testing. In this issue of TreatmentUpdate we present key results from phase II trials with these drugs.

In research programs called Surveyor-I and Surveyor-II, researchers conducted several studies with ABT-493 and ABT-530. In a sub-study of Surveyor-I and Surveyor-II, researchers enrolled participants with HCV genotypes 1 or 2. None of the participants had severe liver injury (cirrhosis) and none of them were co-infected with HIV or hepatitis B virus. The combination of ABT drugs was given for eight consecutive weeks to 34 participants. Researchers found that 33 out of 34 participants with genotype 1 were cured (a rate of 97%). Among the 54 participants who had genotype 2, 53 participants (98%) were cured.

Study details

The average profile of participants upon entering the study was as follows:

  • 60% men, 40% women
  • age – 55 years
  • distribution of genotypes (GT): GT-1a – 70%; GT-1b – 29%; GT–2a/c – 15%; GT–2b – 70%; the remaining GT-2 viruses could not be subtyped
  • viral load – 6.7 logs; more than 38% of participants had a viral load of at least 6 million IU/mL
  • most participants (70%) had mild liver injury, graded as F0 to F1

Results—Genotype 1

Thirty-three out of 34 participants (97%) were cured. The remaining participant had to leave the study after four weeks of treatment because of a diagnosis of cancer; he subsequently died within a couple of months. This cancer diagnosis was unrelated to the study drugs.

Results—Genotype 2

Fifty-three out of 54 participants (98%) were cured. One participant stopped visiting the clinic and could no longer be located.

Resistance

HCV-infected cells produce millions of copies of this virus. During the virus manufacturing process, small changes, or mutations, sometimes occur in HCV’s genetic information. Some of these mutations can help HCV resist the effect of treatment. Researchers found that mutations in HCV were present in two-thirds of participants at the start of the study. However, these mutations did not affect the response to the study medications.

Adverse events

The term adverse events is used to describe symptoms and physical and laboratory-detected complications that can occur in clinical trials. Note that not all adverse events are necessarily related to the study drugs. Some adverse events may arise because of the underlying HCV infection or pre-existing HCV-related complications or even causes unrelated to the disease or study medicine.

Overall, 68% of study participants with GT-1 and 61% of participants with GT-2 developed adverse events. According to the research team, most of these events were of mild intensity. Common adverse events occurred as follows:

  • fatigue – 15%
  • headache – 7%

Lab tests did not detect abnormal increases in liver enzyme levels or the waste product bilirubin. No participant developed anemia of moderate or severe intensity.

There were two adverse events that were not related to the study drugs. The first was the case of cancer previously mentioned. The second was a case of bacterial infection of the skin.

Key points

The combination of ABT-493 and ABT-530 was highly effective when taken for eight consecutive weeks in people with genotype 1 or 2 who did not have cirrhosis regardless of viral load and subtype. The drugs were well tolerated. Further studies are ongoing.

—Sean R. Hosein

REFERENCE:

Poordad F, Felizarta F, Wang S, et al. High SVR rates with the combination of ABT-493 and ABT-530 for 8 weeks in patients with HCV genotype 1 or 2. The International Liver Congress, 13-17 April 2016, Barcelona. Abstract 157.