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Generic sofosbuvir-based therapy underperforms in real-world setting, but is use of suboptimal regimens the reason?

December 10, 2016

Generic sofosbuvir-based combinations may not perform as well as therapy based on branded sofosbuvir-containing regimens, according to result of a study conducted in Qatar and presented to the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to have a sustained virological response 12-weeks post treatment (SVR12) and were also more likely to experience an adverse event, compared to people who received branded drugs.

But the investigators speculate that the generics may have under-performed because of the high proportion of people treated with suboptimal regimens, and believe this deserves further research.

In Qatar, between 0.5 and 1.1% of the local population have chronic hepatitis C virus (HCV) infection, though the prevalence is much higher – 6.3% – among migrants. Sofosbuvir is approved in Qatar for use in interferon-containing and all oral combinations. The country aims to control its HCV epidemic by 2020. However, providing therapy for migrants has been challenging because of restrictions on drug reimbursement costs. Therefore, the treatment of migrants who have HCV infection is relying on the use of generics.

Because of this reliance on generics, investigators designed an observational study comparing the efficacy and safety of HCV treatment regimens based on branded or generic sofosbuvir. Local patients were provided with the branded versions of anti-HCV drugs by their hospital, whereas migrants were required to obtain generics via other sources.

The primary outcomes were SVR12 and drug safety.

The study population consisted of 343 people, with 38% treated with branded medication and 62% with generics. People treated with generics were younger (49 vs 51 years, p = 0.019) and more likely to be male (85% vs 54%, p < 0.001) compared to individuals provided with branded drugs.

The most commonly used combination was sofosbuvir/simeprevir (35%), followed by sofosbuvir/ribavirin (24%), sofosbuvir/interferon/ribavirin (21%), sofosbuvir/ledipasvir (11%), sofosbuvir/daclatasvir (10%), sofosbuvir/ledipasvir/ribavirin (0.6%) and sofosbuvir/interferon (0.3%).

SVR12 data were available for 251 people.

Overall, the branded medication significantly out-performed generics (SVR12 = 91% vs. 74%, p = 0.001). However, among people taking sofosbuvir/simeprevir, the group taking the generics were slightly more likely to attain a SVR12 than those taking branded drugs (95% vs. 90%).

Outcomes for people taking sofosbuvir/ribavirin were especially poor, regardless of whether the branded or generic drugs was used (75% vs. 64%).

Other factors associated with the chances of attaining SVR12 were gender (female, 91% vs male, 78%, p = 0.017), HCV genotype (G1, 92% vs G4, p = 0.041) and cirrhosis status (no cirrhosis, 86% vs cirrhosis, 74%, p = 0.049).

An adverse event was observed in 16% of people overall. But individuals treated with generics were more likely to experience an adverse event compared to those treated with the branded drug (20% vs 10%, p = 0.001).

The most common adverse events were anaemia (4%), increased bilirubin and fatigue (2%), headache (2%), and cough, skin rash and hepatocellular carcinoma (1%).

“In this study, brand-name products showed better effectiveness and safety than generic medications,” conclude the authors. “This observation, though probably driven by the high number of patients on suboptimal regimens such as sofosbuvir/ribavirin and sofosbuvir/interferon/ribavirin, should be explored in future studies.”

By Michael Carter

Reference

Derbala MF et al. Generic versus branded sofosbuvir-based therapy: efficacy and safety in a real world setting. Hepatology Special Issue, The 67th Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting, abstract 2027, Boston, 2016.

Original Article