Back HCV Treatment AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens

AASLD 2016: Generic Sofosbuvir Underperforms in Real World, May Be Due to Suboptimal Regimens


Generic sofosbuvir-based combinations for hepatitis C may not perform as well as branded sofosbuvir-containing regimens, according to a study conducted in Qatar and presented at the recent 2016 AASLD Liver Meeting. People treated with generics were less likely to be cured and more likely to experience adverse events compared to people who received branded drugs. But the investigators speculate that the generics may have underperformed because many people treated were with suboptimal regimens, and believe this deserves further research.

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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 hepatitis C epidemic by 2020. However, providing therapy for migrants has been challenging because of restrictions on drug reimbursement costs. Therefore, the treatment of migrants with HCV infection is relying on the use of generics.

Because of this, 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 branded versions of anti-HCV drugs by their hospital -- sofosbuvir (Sovaldi), sofosbuvir/ledipasvir (Harvoni), simeprevir (Olysio), and/or daclatasvir (Daklinza) -- whereas migrants were required to obtain generics via other sources.

The primary outcomes were sustained virological response at 12 weeks post-treatment (SVR12) and drug safety.

The study population consisted of 343 people, of whom 38% were treated with branded medication and 62% with generics. People treated with generics were younger (49 vs 51 years) and more likely to be male (85% vs 54%) compared to individuals provided with branded drugs. Most patients had HCV genotype 4.

The most commonly used combination was sofosbuvir plus simeprevir (35%), followed by sofosbuvir plus ribavirin (24%), sofosbuvir plus interferon and ribavirin (21%),sofosbuvir/ledipasvir (11%), sofosbuvir plus daclatasvir (10%), sofosbuvir/ledipasvir plus ribavirin (0.6%), and sofosbuvir plus interferon alone (0.3%). SVR12 data were available for 251 people. Most were treated for 12 weeks, although people receiving sofosbuvir plus ribavirin were treated for 24 weeks.

Overall, the branded medication significantly outperformed generics (91% vs 74% SVR12). However, among people taking sofosbuvir plus simeprevir, the group taking the generics was slightly more likely to attain a SVR12 than those taking branded drugs (95% vs 90%).

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

Other factors associated with the chances of attaining SVR12 were gender (91% female 91% vs male 78%), HCV genotype 1 vs 4, and cirrhosis status (no cirrhosis 86% vs with cirrhosis 74%).

Adverse events were observed in 16% of patients overall. But individuals treated with generics were more significantly likely to experience an adverse event compared to those treated with branded drugs (20% vs 10%). The most common adverse events were anemia (4%); increased bilirubin, fatigue, and headache (2%); and cough, skin rash, and hepatocellular carcinoma (1%).

"In this study, brand-name products showed better effectiveness and safety than generic medications," concluded 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."



M Derbala, E Elsayad, O Hajelssedig, et al. Generic versus branded sofosbuvir-based therapy: efficacy and safety in a real world setting. AASLD Liver Meeting. Boston, November 11-15, 2016. Abstract 2027.