AT THE INTERNATIONAL LIVER CONGRESS 2015

VIENNA (FRONTLINE MEDICAL NEWS) – A 12-week, fixed-dose regimen safely and effectively eradicated chronic hepatitis C infection from the first 10 patients with advanced chronic kidney disease in a multicenter U.S. series.

The regimen of three direct antiviral agents is already on the U.S. market. So far, 20 HCV patients with advanced chronic kidney disease have been treated and there have been no cases of virologic failure. All 10 patients who have been followed for at least 4 weeks after completing treatment sustained their virologic response, Dr. Paul J. Pockros said at the meeting sponsored by the European Association for the Study of the Liver.

The series has exclusively enrolled patients with genotype 1 hepatitis C virus (HCV) infection. The seven enrolled patients infected with genotype 1b HCV received the three direct antiviral agents only, the combination of ombitasvir, paritaprevir boosted with ritonavir, and dasabuvir, which together are marketed as Viekira Pak . The 13 patients with a genotype 1a infection received treatment with both the three-drug regimen plus ribavirin, which was effective but resulted in significant hemoglobin reduction in eight patients that required dosage interruptions. All patients were then able to restart and continue treatment, said Dr. Pockros, a gastroenterologist at the Scripps Clinic in La Jolla, Calif.

The efficacy and safety of these three direct antivirals in patients with advanced chronic kidney disease – an estimated glomerular filtration rate (eGFR) of no greater than 30 mL/min/1.73 m2 – contrasts with the caution that exists for another major, direct antiviral agent for hepatitis C eradication, sofosbuvir, which is marketed as Sovaldi as an individual drug and as Harvoni when formulated with ledipavir. The labels for both forms of sofosbuvir say that the drug’s safety and efficacy “has not been established in patients with severe renal impairment (eGFR <30 mL/min/1.73m2) or end stage renal disease (ESRD) requiring hemodialysis. No dose recommendation can be given for patients with severe renal impairment or ESRD.”

A new phase of the trial starting soon will test whether patients infected with genotype 1a HCV can be effectively treated with the three direct antiviral agents alone without ribavirin, Dr. Pockros said. Another soon-to-start aspect of the trial will test the regimen in patients with cirrhosis. The current series has so far enrolled only treatment naive patients without cirrhosis.

The RUBY-1 trial has been run at nine U.S. centers, where researchers enrolled seven patients with stage 4 chronic kidney disease (an eGFR of 15-29 ml/min/ 1.73m2), and 13 patients on hemodialysis and with stage 5 chronic kidney disease, defined as an eGFR of less than 15 mL/min/1.73m2. Fourteen of the 20 enrolled patients (70%) were African American, and 15% were Hispanic, a demographic pattern that is “a fair representation” of U.S. patients with both hepatitis C infection and end-stage renal disease, Dr. Prockros said.

The three direct antivirals tested in the current study are all metabolized in the liver and require no dose modification when used in patients with renal dysfunction. Pharmacokinetic studies done as part of the study showed no differences in blood levels of these drugs in the patients with advanced chronic kidney disease compared with historical patients with better renal function. Several reports published in 2014 documented the efficacy of ombitasvir, paritaprevir plus ritonavir, and dasabuvir for eradicating chronic HCV infection in patients with more normal renal function (N. Engl. J. Med. 2014;370: 1594-1603 , 1604-14 , 1973-82 , 1983-92 ).

RUBY-1 was sponsored by AbbVie, which markets Viekira Pak. Dr. Pockros disclosed ties with AbbVie, Janssen, Bristol-Myers Squibb, Gilead, Merck, Conatus, and Roche Molecular.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

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