July 30, 2019
By Will Boggs MD
NEW YORK (Reuters Health) - A fixed-dose combination tablet containing the generic direct-acting antiviral drugs sofosbuvir and daclatasvir provides high rates of sustained viral response in patients with hepatitis C, according to results from the SD1000 phase 3 clinical trial in Iran.
"Hepatitis C can be cured using simple generic drugs which can be produced for under US$100 per person," Dr. Andrew Hill of the Institute of Translational Medicine, in Liverpool, UK, told Reuters Health by email. "Over 95% of people with hepatitis C could be cured in this way."
The combination of sofosbuvir and daclatasvir has proven effectiveness against all genotypes of the hepatitis C virus (HCV), but no branded fixed-dose combination exists because the original producers are two different pharmaceutical companies with competing interests. In Iran, the fixed-dose combination of sofosbuvir 400 mg and daclatasvir 60 mg has been available from Rojan Pharma (Tehran) for about three years.
At 46 centers in Iran, Dr. Hill and colleagues enrolled 1,361 patients with hepatitis C, most of whom had genotype 1 or 3.
Patients were treated with a single once daily tablet of sofosbuvir/daclatasvir. The recommended treatment duration was 12 weeks for patients without cirrhosis and 24 weeks for those with cirrhosis, but treating physicians were free to select a 12-week treatment duration for patients with cirrhosis and instead, add weight-based ribavirin.
The sustained viral response 12 weeks after the end of treatment (SVR12), the primary endpoint, was 94.7% overall, which included 95.0% of genotype 1, 90.9% of genotype 2, 93.5% of genotype 3, and 100% of genotype 4, the team reports in Clinical Infectious Diseases, online July 10.
SVR12 was higher in patients with no cirrhosis (96.5%) or compensated cirrhosis (93.9%) than in decompensated cirrhosis (79.7%) and slightly higher in treatment-naive patients (95.0%) than in previously treated patients (93.7%).
Adverse events were reported in 33 patients (2.4%), including 32 mild events and one serious adverse event (deemed unrelated to treatment) leading to discontinuation of medicine.
There were 15 deaths during the study, 11 of them in patients with decompensated cirrhosis.
"Worldwide in 2016, for every person cured of HCV using antivirals, another person was newly infected," Dr. Hill said. "So the world is not on course to eliminate HCV given the current rate of treatment."
"At least 5 million people need to be cured of hepatitis C each year for us to reach the World Health Organization (WHO) goal of eliminating HCV worldwide by 2030," he said. "We will need to use low-cost generic antivirals to make elimination affordable. This analysis shows how effective low-cost generic antivirals can be for the mass treatment programs in low- and middle-income countries."
Dr. Dario Cattaneo of ASST Fatebenefratelli Sacco University Hospital, in Milan, Italy, recently reviewed generics for the treatment of HCV. He told Reuters Health by email, "This is a very strong and well-powered study that clearly reassures physicians on the effectiveness and safety of generic antivirals (provided that they are prequalified by WHO)."
"Taking into account the fact that HCV genotyping is not always available in developing countries, this study is important also because it shows the pangenotypic efficacy of this fixed-dose combination," he said. "In other words, with this drug combination HCV genotyping may not be necessary - just treat all the HCV-positive patients, and the WHO 2030 target (no more HCV after 2030) would really be possible!"
The Digestive Disease Research Institute of Tehran University of Medical Sciences funded the study. Two of Dr. Hill's coauthors are employees of Rojan Pharma, and three are stockholders.
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