Combined ruzasvir, uprifosbuvir shows suboptimal HCV pangenotypic efficacy

WASHINGTON — The combination of Merck’s ruzasvir and uprifosbuvir correlated with reduced efficacy in patients with hepatitis C genotype 3 with or without cirrhosis, according to a presentation at The Liver Meeting 2017.

Eric Lawitz

Eric Lawitz, MD, of the University of Texas Health Science Center, Texas Liver Institute in San Antonio, presented phase-2, open-label data on the NS5A inhibitor ruzasvir 180 mg combined with NS5B inhibitor uprifosbuvir 450 mg for 12 weeks. He noted that a combination with a lower dose of ruzasvir correlated with “suboptimal efficacy” in a previous data set.

Eligible participants were either treatment-naive or had previously received treatment with interferon with or without ribavirin. The researchers included patients with or without compensated cirrhosis. Most patients were Caucasian, men and aged 50 years or older.

The analysis included 267 participants with HCV genotype 1 to 4 and a cohort of 219 participants with genotypes 1 to 6. This included 47 patients with genotype 1a, 28 with genotype 1b, 50 with genotype 2, 61 with genotype 3, 56 with genotype 4, three with genotype 5, and 22 with genotype 6.

The overall rate of sustained virologic response was 90%, according to Lawitz. “This includes eight patients who failed for administrative reasons,” he said. “The modified SVR12 rate is 92%.”

Nineteen patients relapsed and two patients discontinued due to adverse events. “Importantly, 14 of the 19 virologic relapsers were genotype 3 patients,” Lawitz said. Three of these relapses had genotype 1a disease. “There was no impact on genotype 1b, 2, 3, 4, 5 or 6 on efficacy regardless of cirrhosis status or baseline resistance-associated substitutions.”

Overall, 76% of patients with genotype 3 achieved SVR. Patients with NS5A resistance had an overall SVR of 74%.

Further, there was no statistical difference between SVR rates in patients with cirrhosis and those without cirrhosis, according to Lawitz. However, he noted that the rate among patients with cirrhosis was 68% vs. 80% for those without cirrhosis.

“Turning our attention to safety, adverse events were frequent, but drug-related adverse events were infrequent, at 33%,” he said, adding that there were seven serious events, none of which investigators determined to be drug-related.

“The overall efficacy of the two-drug regimen of ruzasvir 180 mg and uprifosbuvir 450 mg is suboptimal as a pangenotypic regimen,” Lawitz concluded. “There was lower efficacy in genotype 3. Lower efficacy was seen both in cirrhosis and non-cirrhosis. Baseline resistance-associated substitutions accounted for many, but not all, of the virologic failures. There was potential impact of a baseline Y93 RAS.” – by Rob Volansky

For more information:

Lawitz E, et al. Abstract 61. Presented at: The Liver Meeting; Oct. 20-24, 2017; Washington, D.C.

Disclosure: Lawitz reports being on the advisory committee or review panel of AbbVie, Achillion Pharmaceuticals, Enanta, Gilead, Idenix Pharmaceuticals, Janssen, Merck & Co, Novartis, Regulus and Theravance; receiving grant or research support from AbbVie, Achillion Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Enanta, Gilead Sciences, GlaxoSmithKline, Idenix Pharmaceuticals, Intercept Pharmaceuticals, Janssen, Merck & Co, Novartis, Nitto Denko, Salix and Theravance; and speaking and teaching for AbbVie, Bristol-Meyers Squibb, Gilead, Janssen, Intercept and Merck.