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Three-drug combination yielded high SVR rates in genotype 1
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BOSTON — A triple-drug combination was associated with sustained virologic response rates of approximately 90% in a cohort of patients with genotype 1 disease that included those with cirrhosis, according to findings presented at a press conference during the 2014 Conference on Retroviruses and Opportunistic Infections.
Trevor Hawkins, MD, of the Southwest CARE Center in Santa Fe, N.M., discussed all-oral combination of three drugs from Bristol-Myers Squibb: daclatasvir, asunaprevir and BMS-791325, a non-nucleoside NS5B inhibitor. He said sustained virologic response (SVR) rates of more than 90% were reported among non-cirrhotic patients with genotype 1 disease in pilot studies of this combination.
Larger cohorts, including patients with cirrhosis, were included in the current analysis. Treatments were administered twice a day to support coformulation development, according to the results.
All 166 treatment-naive patients received daclatasvir 30 mg and asunaprevir 200 mg. Eighty patients were randomly assigned 75 mg BMS-791325 and 86 patients received 150 mg of the same drug. The treatment duration was 12 weeks.
The investigators stratified the randomization process by genotype 1 subtype and presence of cirrhosis.
HCV RNA less than the lower limit of quantification (LLOQ; 25 IU/mL) at 12 weeks served as the primary outcome measure.
The treatment cohorts demonstrated similar baseline characteristics. The study population was 56% men, 83% white, 82% genotype 1a, 67% IL28B non-CC genotype and 9% cirrhotic.
The primary endpoint was SVR at week 12. Overall, this was reached by 92.2% of patients in the 75-mg group and 91.7% of those in the 150-mg group. All patients with cirrhosis who received the 75-mg dose, and 71% who received the 150-mg dose reached the primary endpoint, according to Hawkins.
On-treatment virologic breakthrough occurred in five of 166 patients. Post-treatment relapse occurred in six of the 166 patients. All of these patients, Hawkins said, were in the genotype 1a group.
One patient in each treatment arm discontinued therapy as a result of an adverse event. These events included an unrelated esophageal neoplasm and throat tightness. Headache, diarrhea, fatigue and nausea comprised the most commonly reported events but did not lead to mortality or grade 3 or 4 events.
A single event of grade 3 elevated aspartate aminotransferase and a single event of grade 3 total bilirubin occurred in separate patients.
“This all-oral combination regimen was well tolerated with very few discontinuations,” Hawkins said.
He added that the investigators attempted to determine what predicted the 11 virologic failures that occurred in the study.
“The only thing that came out as predictive was genotype 1a,” he said. “There were no failures in 1b. We tried to look at baseline polymorphisms to see if there was a pattern of resistance-associated polymorphisms that we could tease out, but there were no obvious correlations.”
Hawkins said the triple regimen continues to undergo analysis in various patient populations as part of the UNITY 1 and UNITY 2 trials.
For more information:
Everson GT. Abstract #25. Presented at: The CROI 2014; March 3-6, 2014; Boston.
Disclosure: Hawkins reports associations with companies including Abbvie GS, Bristol Myers Squibb, Gilead, GlaxoSmithKline, Janssen, Merck, Salix, Sangamo, Vertex and ViiV.