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Zepatier safe, efficacious in general, problematic HCV patient populations
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BARCELONA — Data from a phase 3 trial presented at the International Liver Congress suggested that Zepatier is noninferior to and better tolerated than a Sovaldi-based regimen for hepatitis C virus infection treatment.
In addition, the once-daily, fixed-dose treatment appears to remain effective among patients who have inherited blood disorders, or inject drugs and receive opioid agonist therapy, according to additional data presented at the conference.
Improved SVR, fewer AEs compared with Sovaldi-based regimen
In the C-EDGE Head-to-Head trial, researchers enrolled 255 patients with HCV infection genotypes 1a, 1b and 4 to receive either Zepatier (elbasvir/grazoprevir, Merck; EBR/GZR; n = 129) or a regimen of Sovaldi (sofosbovir, Gilead Sciences) and peginterferon alpha 2b/ribavirin (SOF/PR; n = 126) for 12 weeks. Enrollment was conducted at multiple sites in the European Union, Norway and Turkey. Researchers reported sustained viral response (SVR) rates, safety and tolerability data taken at 12 weeks’ follow-up. Patients in the study cohort were predominantly white and an average age of 48 years. One-quarter were treatment-experienced, 17% had compensated cirrhosis, 82% were infected with HCV genotype 1b, and all completed treatment.
At week-12, 99% of patients assigned to receive EBR/GZR demonstrated SVR (one discontinuation), as opposed to the 90% rate observed among the SOF/PR arm (11 virologic failures, one discontinuation). While 52% of patients in the EBR/GZR group reported one or more adverse events (AE) and only one serious AE, these respective outcomes were reported by 93% and 4% of those given SOF/PR.
“The [EBR/GZR] regimen showed superior SVR rates and improvement on pre-specified safety endpoints compared to the [SOF/PR] regimen in these genotype 1- or 4-infected patients,” Jan Sperl, MD, of the Institute for Clinical and Experimental Health in Prague, said in a press release. “[SOF/PR] continues to be a prescribed treatment regimen in many regions, and this comparative study vs. combination treatment with [EBR/GZR] provides interesting and important insights.”
IDU, persons with inherited blood disorders demonstrate improved outcomes
Favorable outcomes also were reported by two other randomized trials examining EBR/GZR treatment among special patient populations with HCV infection.
In C-EDGE CO-STAR, researchers enrolled a cohort with HCV genotype 1, 4 or 6 infection who inject drugs and were currently receiving opioid agonist therapy (OAT). These 301 patients received either EBR/GZR (n = 201) or placebo (n = 100) once daily for 12 weeks. In addition, the participants completed a standardized health survey upon enrollment to determine health-related quality of life (HRQOL) and repeated the survey at treatment weeks 4 and 12 and at follow-up weeks 4 and 12. Researchers examined these surveys to determine any trends in mental or physical health scores from baseline to the end of treatment.
Although initial HRQOL scores were similar between groups, the mean scores of individual and summary physical and mental summary scores were improved over the course of treatment. Average scores declined, however, in all areas for the placebo group, according to the researchers, demonstrating EBR/GZR’s beneficial effect on infected injection drug users receiving OAT.
Similarly, researchers conducting the C-EDGE IBLD trial examined morbidity and mortality outcomes among HCV infection patients with inherited blood disorders, such as hemophilia, beta thalassemia, von Willebrand disease and sickle cell anemia. They recruited 159 treatment-experienced or treatment-naive patients to receive either immediate treatment of EBR/GZR for 12 weeks (n = 107), or deferred placebo treatment for 12 weeks followed by EBR/GZR (n = 52). Randomization was stratified by cirrhosis status and inherited blood disorder type, and the primary endpoint was 12-week SVR.
Following treatment, 93% of the immediate treatment group achieved 12-week SVR, with five of the six patients who relapsed demonstrating detectable NS5A resistance-associated polymorphisms at baseline. Compared with the deferred treatment group, fewer patients reported serious AE (3 vs. 6), and no patients discontinued treatment due to AEs. Treatment had no effect on pre-defined hematological parameters, and did not hamper management of underlying blood disorders.
“We continue to build on the data that supported the recent U.S. FDA approval of Zepatier with additional studies that provide clinical evidence about Zepatier in multiple patient populations,” Eliav Barr, MD, vice president of infectious diseases at Merck Research Laboratories, said in a press release. “Merck remains committed to the fight against chronic hepatitis C through our ongoing clinical programs exploring diverse patient groups and areas of unmet need.” – by Dave Muoio
References:
Arduino JM, et al. Abstract THU-225. Presented at: International Liver Congress; April 13-17, 2016; Barcelona, Spain.
Hezode C, et al. Abstract SAT-128. Presented at: International Liver Congress; April 13-17, 2016; Barcelona, Spain.
Sperl J, et al. Abstract PS002. Presented at: International Liver Congress; April 13-17, 2016; Barcelona, Spain.
Disclosures: Barr is an employee of Merck. Sperl reports research grants from Gilead Sciences and Janssen Cilag, as well as other financial relationships with AbbVie, Gilead Sciences, Janssen Cilag and Merck. Please see the abstracts for a list of all other authors’ relevant financial disclosures.