A review of evidence of the clinical safety and efficacy of Zepatier found that the hepatitis C virus treatment appears to have a less risky safety profile than Sovaldi and a similar safety profile as Harvoni.
Reviewing evidence of the clinical safety and efficacy of the hepatitis C virus (HCV) treatment Zepatier (a combination of elbasvir and grazoprevir) compared with 2 other HCV treatments—Harvoni (sofosbuvir, ledipasvir) and Sovaldi (sofosbuvir)—Advera Health Analytics concluded in a new report that Zepatier appears to have a less risky safety profile than Solvaldi and a similar safety profile as Harvoni.
According to Advera’s report, as a standalone therapy Harvoni appears more effective in treatment-naïve patients, while Zepatier and Harvoni seem to have similar efficacy in treatment-experienced patients.
Zepatier, Harvoni, and Sovaldi are direct-acting antiviral (DAA) agents that treat HCV. DAAs have revolutionized HCV treatment, the report noted, with some drugs improving the sustained virologic response (SVR) rates to 80%-90%, while reducing the adverse events (AEs) associated with treatment compared with the previous standard of care, which was a combination of pegylated interferon alpha and ribavirin.
The analysis noted that Harvoni and Sovaldi are associated with AEs such as cardiac arrest, suicidal ideation, and suicide, while Zepatier’s label does not include these AEs. Initial analysis of Zepatier’s label showed comparatively fewer AEs (29 vs 41 for Sovaldi). Liver cirrhosis, the only Important Medical Event (IME) listed on the label, is largely associated with HCV and not with the drug.
Advera identified potential future FDA label changes for Sovaldi’s serious AEs: progressive multifocal leukoencephalopathy, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced liver injury. Five of Sovaldi’s 41 AEs are rated as serious enough to be IMEs, including cardiac arrest, suicide, suicidal ideation, and pancytopenia.
Harvoni has almost the same number of labeled AEs as Zepatier and 3 AEs classified as IME-level serious on its label.
“Overall, with no serious labeled AEs, fewer labeled AEs than Sovaldi, and nearly the same number of labeled AEs as Harvoni, Zepatier appears to have a better safety profile than Solved and a similar profile as Harvoni,” the report noted.
Summarizing all the clinical trials conducted for approval of all 3 medications, Harvoni appears to display a higher SVR rate (99%) in treatment-naïve patients than Zepatier (95%) and Sovaldi (90%). Zepatier and Harvoni appeared to have similar efficacy in treatment-experienced patients as standalone therapy (SVR, 94%). In patients co-infected with HIV, Harvoni and Zepatier may appear to have similarly high SVRs (96% and 95%, respectively) than Sovaldi (76%).
DAAs are very expensive treatments. Sovaldi costs $84,000—it is $23,810 per prescription and has an additional prescription cost burden of $72.53/prescription, according to Advera’s proprietary calculation of downstream medical costs associated with AE/drug combinations, which is a huge downstream medical expense of $9,570,000 annually based on postmarketing patient reports of AEs. A single 12-week regimen of Harvoni is estimated to cost $95,000.
Zepatier is priced at $54,600 for a 12-week course and is thus less expensive than its competitors. (A fourth DAA, Viekira Pak [not part of this report], is $83,319.)