Drugs to treat the hepatitis C virus (HCV) are jostling for headlines as an array of new medications hits the market. Here’s an update on one drug combination on the fast track and warnings about drug interactions for two drugs already on the market.
On the fast track
In April 2015, Merck announced that the US Food and Drug Administration (FDA) had granted breakthrough therapy (BT) designation for its daily oral HCV tablet combining grazoprevir and elbasvir. Grazoprevir is an NS3/4A protease inhibitor that stops the serine protease enzyme from cutting a long protein into smaller functional units that HCV needs to reproduce. Elbasvir is an NS5A replication complex inhibitor, blocking the action of enzymes HCV needs to complete its life cycle.
In 2012, the FDA created the BT designation to put drugs on a faster track for review and acceptance. BT-designated drugs are required to treat serious or life-threatening diseases. They must provide preliminary data showing significant improvement over existing medications. In 2013, grazoprevir/elbasvir received the BT designation to treat patients with HCV genotype 1, the most common and most difficult to treat. However, the BT designation was rescinded in February 2015 because other HCV drugs were considered more effective.
In April 2015, the FDA reinstated grazoprevir’s/elbasvir’s BT designation after Merck provided phase 3 clinical trial data on two subsets of patients: those with genotype 4, and those with genotype 1 who had end-stage liver disease and were on dialysis for kidney failure. Data from the C-EDGE trials showed promising results for treatment-naïve (previously untreated) patients and treatment-experienced (previously tried and failed other HCV regimens) patients.
Results of the C-EDGE clinical trial showed that of the 105 treatment-experienced patients with genotypes 1, 4 and 6 who took grazoprevir/elabasvir for 12 weeks, 92.4% had a sustained viral response (SVR), an indication that the body had cleared the virus 12 weeks after therapy ended. When ribavirin was added, SVR was 94.2%.
The success rates were even higher for treatment-experienced patients who took the drugs for 16 weeks. The genotype 1, 4 and 6 group without ribavirin achieved an SVR of 92.4%; the group with additional ribavirin had an SVR of 97.2%. The main side effects were diarrhea, fatigue, headache and nausea, but no patients dropped out of the study because of these. (When HemAware went to press, Merck had filed a New Drug Application with the FDA.)
Drug interactions with Sovaldi® and Harvoni®
Gilead’s blockbuster HCV drugs Sovaldi® (sofosbuvir) and Harvoni® (ledipasvir/sofosbuvir) will soon have a new warning on the label, according to the FDA. Some patients who took Sovaldi and Harvoni with another HCV direct-acting antiviral drug and amiodarone, a heart arrhythmia drug, experienced life-threatening complications. One patient died of cardiac arrest; others needed a pacemaker after their heart rate dropped to very low levels, called bradycardia. Bradycardia developed in the patients within hours or a couple of days, even up to two weeks later.
Also, be aware that St. John’s wort, an herbal product used to treat depression and other conditions, and rifampin, an antibiotic prescribed for tuberculosis, should not be taken with Harvoni. Both significantly decrease the plasma concentrations of Harvoni, limiting its therapeutic effectiveness.