Compounds with a graded row

Ordered by rung, strongest first. The rung rates the study design; the chip beside it says what the study measured. Both are needed.

1. Boceprevir

   human RCT Direct outcome Not approved for this condition

   Who was studied

   previously untreated adults with chronic HCV genotype 1, n=1097 (938 non-black, 159 black), 44-48 weeks, in the phase 3 SPRINT-2 trial

   No longer marketed. Merck discontinued manufacture and distribution in the United States during 2015, and the European marketing authorisation for Victrelis was withdrawn on 29 June 2018 at the holder's request, so there is no current approval anywhere on file. In its era SPRINT-2 measured sustained virological response and found 67-68% with boceprevir added to peginterferon/ribavirin versus 40% with peginterferon/ribavirin alone in the non-black cohort, and 42-53% versus 23% in the black cohort; anaemia occurred in 49% of boceprevir recipients versus 29% of controls.

   Source PubMed Central 2 primary sources read for this row

2. Sofosbuvir

   human RCT Direct outcome Approved for this condition

   Who was studied

   adults with chronic HCV, genotypes 1-4; NEUTRINO enrolled n=327 treatment-naive adults (89% genotype 1, 9% genotype 4) with or without compensated cirrhosis; FUSION enrolled previously treated genotype 2/3 patients

   FDA-approved (Sovaldi, 2013) for chronic hepatitis C genotypes 1, 2, 3 and 4 in adults without cirrhosis or with compensated cirrhosis, and for genotype 2 or 3 in children aged 3 and over, always in combination regimens. The outcome measured was sustained virological response at 12 weeks: 90% (289/320) in treatment-naive genotype 1/4 patients on the 12-week peginterferon/ribavirin combination in NEUTRINO, 95% in treatment-naive genotype 2 in FISSION, and 82% in previously treated genotype 2 in FUSION.

   Source DailyMed — the FDA label 2 primary sources read for this row

3. Telaprevir

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults with genotype 1 chronic hepatitis C and compensated liver disease including cirrhosis, both treatment-naive (ADVANCE) and previously interferon-treated (REALIZE)

   No longer marketed. The EU authorisation for Incivo expired on 22 September 2016 because Janssen-Cilag chose not to renew it after interferon-free regimens arrived, and the US product Incivek was withdrawn in 2014, so there is no current approval on file. Sustained virological response was the registrational outcome, reported at 75% for 12 weeks of telaprevir with peginterferon/ribavirin versus 44% for peginterferon/ribavirin alone in treatment-naive genotype 1 patients in ADVANCE; the label carried warnings on serious and fatal skin reactions and on severe anaemia.

   Source EMA 2 primary sources read for this row

4. Thymosin alpha-1

   human RCT Direct outcome Not approved for this condition

   Who was studied

   adults aged 18-70 with chronic hepatitis C who had not responded to prior peginterferon plus ribavirin, n=552, 48 weeks of treatment with outcome assessed at week 72; genotype not specified in the registry record; advanced (Child-Pugh B/C) cirrhosis excluded

   Studied only as an adjunct added to peginterferon alfa-2a plus ribavirin, never as primary therapy, and not approved for hepatitis C by the FDA or EMA. This double-blind phase 3 trial in prior non-responders measured sustained virological response as its primary endpoint and the published result (J Viral Hepat 2012, doi 10.1111/j.1365-2893.2011.01524.x) reported 12.7% with thymosin alpha-1 versus 10.5% with placebo, a difference that was not statistically significant (p=0.407). No trial of thymosin alpha-1 alongside modern direct-acting antivirals is on file.

   Source ClinicalTrials.gov 1 primary source read for this row

Checked, and nothing recorded

1 compound was checked against hepatitis c and produced no gradeable row.

• Thymopentin — checked, no row on file

A compound is here because someone looked and the sources did not support a row — not because nobody looked. Under the rubric, uncertainty resolves to no row, and a row resting on a vendor page or a clinic blog is worse than no row at all.