The National Institute for Health and Care Excellence (NICE) invited Gilead, the company manufacturing
ledipasvir-sofosbuvir (LDV/SOF), to submit evidence for the clinical effectiveness and cost-effectiveness of
LDV/SOF for treating Chronic Hepatitis C. The School of Health and Related Research (ScHARR) Technology
Assessment Group was commissioned as the Evidence Review Group (ERG). This paper describes the
company’s submission (CS), the ERG review and the subsequent decision of the NICE Appraisal Committee
(AC). The ERG produced a critical review of the clinical effectiveness and cost-effectiveness evidence of
LDV/SOF based upon the CS.
The clinical effectiveness data for LDV/SOF were taken from ten trials, comprised of three Phase III trials and
seven Phase II trials. Trials compared different durations of LDV/SOF, with and without ribavirin (RBV). There
were no head-to-head trials comparing LDV/SOF with any comparator listed in the NICE scope. Data from the
trials were mostly from populations with genotype 1 (GT1) disease, although some limited data were available
for populations with genotypes 3 and 4. For GT1 treatment-naïve patients, sustained viral response for 12 weeks
(SVR12) rates for LDV/SOF ranged from 93.1% to 99.4% for subgroups of patients with non-cirrhotic disease,
whilst SVR rates of 94.1% to 100% were reported for subgroups of patients with compensated cirrhosis. For
GT1 treatment-experienced patients, SVR12 rates ranging from 95.4% to 100% were reported for subgroups of
non-cirrhotic patients and SVR rates ranging from 81.8% to 100% were reported within subgroups of patients
with compensated cirrhosis.
Comparator data were not searched systematically as part of the submission, but were based on the company’s
previous NICE submission of sofosbuvir, with additional targeted searches.
The ERG’s critical appraisal of the company’s economic evaluation highlighted a number of concerns. The
ERG’s base case analyses suggested that the incremental cost effectiveness ratios (ICERs) for LDV/SOF
(+RBV) are dependent on a) treatment durations, b) whether patients have been previously treated and c)
whether patients have liver cirrhosis or not.
The AC concluded that it was appropriate to use the approach taken in the ERG’s exploratory analyses, in line
with the marketing authorisation, which considered people with and without cirrhosis separately, and estimated
the cost-effectiveness for each recommended treatment duration of LDV/SOF.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)