Published: Nov 10, 2014
By Michael Smith, North American Correspondent, MedPage Today
BOSTON -- Clinical trials for some of the new direct-acting agents against hepatitis C (HCV) have yielded some impressive efficacy numbers. But how well do the drugs stack up in the real world?
Pretty well, according to studies presented here at the American Association for the Study of Liver Diseases annual meeting.
"Real world data are generally consistent with phase II and II trial data," concluded Donald Jensen, MD, of the University of Chicago Medical Center.
Cure rates are "comparable to rates reported in clinical trials," said Douglas Dieterich, MD, of Mount Sinai Hospital in New York City.
The two presented back-to-back analyses of separate cohorts of patients treated over the past year with regimens containing sofosbuvir (Sovaldi) including the off-label (at the time) combination of sofosbuvir and simeprevir (Olysio).
Jensen discussed data collected by the HCV-Target consortium of academic and community medical centers in North America and Europe, which has been collecting information on 2,063 patients treated with sofosbuvir-containing regimens since mid-April.
They include 384 who started on a regimen of sofosbuvir combined with pegylated interferon and ribavirin, the regimen approved by the FDA for patients with HCV genotypes 1 and 4, and 667 who were treated with sofosbuvir and ribavirin, the regimen approved for patients with genotypes 2 and 3.
The cohort also includes 784 patients who were treated with sofosbuvir and simeprevir, which was only approved (for genotype 1 patients ) last month, and 228 who got those two drugs plus ribavirin.
Since treatment durations vary, Jensen presented data on the so-called SVR4 -- an absence of detectable HCV RNA 4 weeks after the end of treatment. HCV is regarded as cured when there is no detectable RNA 12 weeks after the end of therapy, the SVR12.
But, Jensen said, among those who have reached the 12-week mark, the positive predictive value of SVR4 for SVR12 was between 94.4% and 98.2%, while the negative predictive value was 100% across all regimens.
The bottom line, he reported, was that SVR4 rates were:
- 85% for sofosbuvir with interferon and ribavirin in genotype 1 patients.
- 90% for sofosbuvir plus ribavirin in genotype 2 patients.
- 89% for genotype 1 patients getting sofosbuvir and simeprevir, with or without ribavirin.
Interestingly, he said, the use of ribavirin produces no difference in outcomes across various subcategories of patients with genotype 1 treated with sofosbuvir and simeprevir.
The results in sofosbuvir/simeprevir patients are extremely good, considering that many of the patients would not have been eligible for the pivotal COSMOS trial that led to approval of the combination, commented Mark Sulkowski, MD, of Johns Hopkins University, who was one of the investigators on that study.
For instance, he said, 60% of patients in the HCV-Target cohort were cirrhotic, while COSMOS had a much smaller number of patients with cirrhosis and were generally healthier than those in the HCV-Target cohort.
"You've got a clinical trial, in this case COSMOS, and now you've got the translation into a large number of very sick patients with hepatitis C," he told MedPage Today, "and it shows that these drugs do work very well in real-world clinical practice."
Sulkowski presented a separate, more detailed analysis of the sofosbuvir/simeprevir patients in the HCV-Target group.
Meanwhile, Dieterich said, much the same results came out of analysis of 955 patients whose data was obtained from electronic records in the TRIO network of pharmacies.
His analysis included 822 patients intended to be treated for 12 weeks with the same regimens as the HCV-Target cohort, which had some longer treatment periods.
Among the 822, Dieterich said, the overall SVR12 was 79%, but the group included 79 people who dropped out. The SVR12 among those who completed treatment -- the per-protocol cohort of 743 patients -- was 88%.
The rates are "remarkably high, considering the real-life heterogeneous population here," Dieterich said.
Broken down by genotype and regimen, the intent-to-treat SVR12s were: For sofosbuvir, interferon, and ribavirin 72% in genotype 1 and 67% in genotypes 4, 5, and 6 combined; for sofosbuvir plus ribavirin 50% for genotype 1 and 84% for genotype 2, and for sofosbuvir and simeprevir, plus or minus ribavirin 82% for genotype 1.
The most important predictor of response was cirrhosis, Dieterich said.
Both researchers said the drugs under study were generally well tolerated, with no new safety signals.
The HCV-Target consortium is sponsored by Genentech, Kadmon, Janssen, Merck, Vertex, AbbVie, Bristol Myers Squibb, Gilead, and GSK. Jensen disclosed relevant relationships with AbbVie, Boehringer, Bristol Myers Squibb, GSK, and Janssen.
Dieterich disclosed relevant relationships with AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Idenix Pharmaceuticals, Merck, and Janssen Therapeutics. He did not report support for his study.
Sulkowski disclosed relevant relationships with Merck, AbbVie, Idenix, Janssen, Gilead, BMS, Pfizer, BIPI, and Vertex.
Primary source: American Association for the Study of Liver Diseases
Source reference: Dieterich D, et al "Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network" AASLD 2014; Abstract 46.
Additional source: American Association for the Study of Liver Diseases
Source reference:Jensen DM, et al "Safety and efficacy of sofosbuvir-containing regimens for hepatitis C: Real-world experience in a diverse, longitudinal observational cohort" AASLD 2014; Abstract 45.