Advances in Medications to Treat Hepatitis C
Recent advances in the number and types of medications available to treat Hepatitis C give you and your doctor more options to consider when deciding on a treatment plan. These advances have made treatment regimens shorter in duration, less difficult to tolerate and more effective.
What follows is a general outline of the main indications for each drug approved by the U.S. Food and Drug Administration (FDA) to treat Hepatitis C. The drugs are listed in chronological order by date of approval, allowing you to see the advances in medications used to treat HCV infection.
Until a few years ago, there were only two drugs approved by the FDA for Hepatitis C treatment:
Pegylated interferon (Peg-IFN)
Interferon is similar to a protein your body makes to fight off infection. Pegylated interferon is a long-acting form of interferon that’s administered as an injection. It was initially used alone, but later was always used with ribavirin. The first direct-acting antiviral medications were also given with interferon. Interferon is an injection with significant side effects, and many people with HCV were not able to take it or stopped therapy due to these side effects.
In the United States, the more recently-approved stronger oral medications have largely replaced interferon. Interferon is not recommended for genotypes 1, 2 and 4 and is occasionally used in genotype 3. Interferon use is expected to decrease in other countries as all-oral treatment options become available.
Ribavirin, taken by mouth, can never be used alone to treat Hepatitis C. Initially, it was used in combination with interferon, which increased the chances of getting rid of the virus from your body. Presently, it’s often used in combination with one of the newly approved drugs.
The FDA approved two new medications that are part of a drug group called protease inhibitors:
VICTRELIS (boceprevir) and INCIVEK (telaprevir)
These drugs directly attack the Hepatitis C virus to stop it from reproducing and are referred to as direct-acting antivirals (DAAs). The protease inhibitors were approved to be used in people with HCV genotype 1 in combination with Peg-IFN/RBV therapy. They could not be used alone; using Peg-IFN/RBV plus one of the protease inhibitors was called triple therapy. These medications were no longer used after interferon-free regimens became widely available in 2014.
The FDA approved the first once-daily protease inhibitor:
It received its initial FDA approval in combination with Peg-IFN/RBV therapy, but few people received this regimen. Broad use of simeprevir occurred when it was used in combination with a newer drug, sofosbuvir (SOVALDI). This all-oral regimen was initially prescribed off-label (meaning that it wasn’t part of the FDA-approved labeling) for genotype 1 patients and was offered with and without ribavirin. FDA approval for the simeprevir and sofosbuvir combination was ultimately received in November 2014.
The FDA approved a new medication that is a part of a drug group called polymerase inhibitors. It works by blocking a specific protein the Hepatitis C virus needs to grow. It is called:
Sofosbuvir, a once-daily pill, was approved to treat HCV genotypes 1, 2, 3 and 4. This was the first drug that allowed genotype 2 and 3 patients to be treated with pills only, offering an interferon-free regimen with ribavirin. The first line therapy for genotype 1 and 4 patients became a 12-week combination regimen with peginterferon and ribavirin. Patients ineligible for interferon could be offered a 24-week regimen of sofosbuvir and ribavirin.
Sofosbuvir was the first HCV drug with the initial FDA approval inclusive of people who had HIV-HCV co-infection.
The FDA approved the first combination pill to treat Hepatitis C, offering people with HCV genotype 1 an all-oral treatment regimen:
This once-daily pill combined sofosbuvir (Sovaldi) and a new drug called ledipasvir. These medications are part of the class of drugs called direct-acting antivirals (DAAs), which interfere with the enzymes the hepatitis C virus needs to multiply.
Harvoni was approved to treat adults with HCV genotype 1, the most common form of HCV in the U.S. This was the first drug that allowed people with genotype 1 to be treated with only one pill, eliminating the need for weekly injections of interferon or a second antiviral, ribavirin, both of which are challenging to take and tolerate.
In clinical trials, Harvoni cured HCV after 12 weeks of treatment in about 94% of people who took it.
Additional Approvals – The FDA has since approved the following supplemental indications for Harvoni:
- November 2015: Approved for expanded use in patients with HCV genotype 4, 5 and 6 and in patients co-infected with HIV. Additionally, Harvoni plus ribavirin for 12 weeks was approved as an alternate therapy to 24 weeks of Harvoni for treatment-experienced, genotype 1 patients with cirrhosis.
- February 2016: Harvoni in combination with ribavirin for 12 weeks was approved for use in HCV genotype 1 or 4 liver transplant recipients without cirrhosis or with compensated cirrhosis, and for HCV genotype 1 patients with decompensated cirrhosis including those who have undergone liver transplantation.
The FDA granted simeprevir (OLYSIO) an additional approval to be used in combination with sofosbuvir (SOVALDI) as a once-daily, all-oral, interferon and ribavirin-free treatment for adults with genotype 1 HCV infection. (Previous to this, simeprevir had to be used in combination with Peg-IFN/RBV therapy, as outlined above.) This approval gave people with genotype 1 another all-oral treatment option.
The FDA approved a new combination medicine, which can be given with or without ribavirin, to treat adults with genotype 1 HCV infection, including people who have a certain kind of cirrhosis (compensated):
VIEKIRA PAK (ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets)
Viekira Pak, an all-oral interferon-free regimen, is also approved for HCV/HIV co-infection and people who have had a liver transplant. It is not for people with advanced cirrhosis (decompensated). If you have cirrhosis, you should talk with your healthcare provider before taking Viekira Pak.
In clinical trials, Viekira Pak cured 97% of people with HCV genotype 1 including people new and experienced to treatment, and people with compensated cirrhosis.
Additional Approval – The FDA has since approved the following:
- July 2016: The FDA approves Viekira XR, a once-a-day extended release version of Viekira Pak for genotype 1 HCV infection. Viekira XR consists of the same ingredients of Viekira Pak (ombitasvir,/paritaprevir,/ritonavir tablet; dasabuvir tablet) combined into one tablet, offering more convenient dosing. Viekira XR, which can be given with or without ribavirin, is indicated for patients with HCV genotype 1 infection, including those with compensated cirrhosis; it is not for people with decompensated cirrhosis.
The FDA approved two new drugs – TECHNIVIE for the treatment of HCV genotype 4 and DAKLINZA for the treatment of HCV genotype 3.
Technivie was approved for use in combination with ribavirin for the treatment of HCV genotype 4 in patients without scarring and cirrhosis. This was the first treatment option for people with genotype 4 that does not require co-administration of interferon. The three drugs included in Technivie are also included in Viekira Pak, previously approved for the treatment of HCV genotype 1.
In clinical trials, once daily doses of Technivie with ribavirin for 12 weeks cured 100% of the people with HCV genotype 4 without cirrhosis. The most common side effects of Technivie plus ribavirin were fatigue, weakness, nausea, insomnia, itching (pruritis), and other skin reactions.
Elevation of liver enzymes to greater than five times the upper limit of normal occurred in approximately 1% of clinical trial participants. This occurred more frequently in women taking contraceptives containing ethinyl estradiol. Contraceptives that contain this must be discontinued prior to starting Technivie. It’s recommended that liver enzyme testing be performed during the first four weeks of treatment, and as clinically indicated thereafter.
Daclatasvir (Daklinza) – part of the class of drugs called direct acting anitvirals or DAAs – was approved for use with sofosbuvir (Sovaldi) to treat HCV genotype 3 infections. Daklinza is the first drug that demonstrated safety and efficacy in treating HCV genotype 3 without the need for co-administration of interferon or ribavirin.
In clinical trials, 152 treatment-naïve (people who haven’t previously received HCV treatment) and treatment-experienced (people who have previously received HCV treatment) adults received Daklinza 60 mg plus sofosbuvir 400 mg once daily for 12 weeks. At 12 weeks post-treatment, their blood was tested to see if the hepatitis C virus was no longer detectable, indicating they achieved a sustained virologic response (SVR 12), or cure. The results were as follows:
- Treatment-naïve patients with no cirrhosis: 98% achieved SVR
- Treatment-naïve patients with cirrhosis: 58% achieved SVR
- Treatment-experienced patients with no cirrhosis: 92% achieved SVR
- Treatment-experienced patients with cirrhosis: 69% achieved SVR
Daklinza labeling carries a statement informing prescribers that SVR rates are reduced in patients with HCV genotype 3 infected patients with cirrhosis.
The most common side effects of Daklinza with sofosbuvir were fatigue and headache. Daklinza carries a warning that serious slowing of the heart rate (symptomatic bradycardia) and cases requiring pacemaker intervention have been reported when amiodarone (brand names Cordarone, Pacerone) is co-administered with sofosbuvir in combination with another HCV direct-acting antiviral, including daclatasvir. Since taking amiodarine with sofosbuvir can lead to dangerous slowing of the heart, co-administration of amiodarone with sofosbuvir, in combination with Daklinza, is not recommended.
Additional Approval – The FDA has since approved the following supplemental indications for Daklinza:
- February 2016: Approved in combination with sofosbuvir (with or without ribavirin) for HCV genotypes 1 and 3 including challenging-to-treat patients who have HIV-1 coinfection, advanced cirrhosis, or post-liver transplant recurrence of HCV.
The FDA approved a new medicine to treat adults with chronic HCV genotypes 1 or 4 infection, including those with compensated cirrhosis, HIV-1 co-infection, or severe kidney disease and on dialysis.
ZEPATIER (elbasvir 50 mg/grazoprevir 100 mg)
Zepatier is a once-daily, fixed-dose combination tablet, which can be given with or without ribavirin, to adults who have or have not previously received HCV treatment. It is not for use in people with moderate or severe (decompensated) liver disease. A 12-week, once-daily regimen is recommended for the vast majority of people, although a 16-week course has been approved for a certain subset of patients.
In a broad clinical trial program, six studies were done in 1.373 diverse patients with chronic HCV gentoypes 1 or 4. At 12 weeks post-treatment, their blood was tested to see if the hepatitis C virus was no longer detectable, indicating they achieved a sustained virologic response (SVR 12), or cure. Cure rates ranged from 94% – 97% in genotype 1-infected patients, and 97% – 100% in genotype 4-infected patients. Elevation of liver enzymes to greater than five times the upper limit of normal occurred in approximately 1% of clinical trial participants, generally at treatment week 8. Your healthcare professional will do blood tests to check your liver enzymes before and during treatment with Zepatier.
The most common side effects of Zepatier when used without ribavirin include fatigue, headache and nausea. When Zepatier is used with ribavirin, common side effects include low red blood counts (anemia), headache, fatigue, shortness of breath, and rash or itching.
Some medicines cannot be taken with Zepatier – including prescription and over-the-counter medicines, vitamins, and herbal supplements – so tell your healthcare provider about all the medicines you take.
The FDA approved a new combination medicine, the first therapy approved to treat all HCV genotypes (1, 2, 3, 4, 5, or 6). It is also the first single tablet regimen approved for the treatment of patients with HCV genotype 2 and 3, without the need for ribavirin.
EPCLUSA (sofosbuvir 400mg/velpatasvir 100 mg)
Epclusa is a once-daily, fixed-dose combination tablet approved for the treatment of adults with chronic HCV genotype 1-6. Epclusa for 12 weeks was approved in patients without cirrhosis or with compensated cirrhosis, and in combination with ribavirin for patients with decompensated (advanced) cirrhosis.
International clinical trials involving 1,035 patients with genotype HCV 1-6 without cirrhosis or compensated cirrhosis, received 12 weeks of Epclusa. Twelve weeks after treatment, their blood was tested to see if the hepatitis C virus was no longer detectable, indicating they achieved a sustained virologic response (SVR 12), or cure; 1,015 trial participants (98%) achieved SVR12 and were considered cured.
In another study, 267 patients with HCV genotype 1-6 with decompensated cirrhosis received 12 weeks of Epclusa with or without ribavirin, or 24 weeks of Epclusa. Patients that received 12 weeks of Epclusa with ribavirin had the highest cure rate (94%), compared with those who received Epclusa for 12 weeks (83% cured) or 24 weeks (86% cured).
The most common side effects of Epclusa were headache and fatigue. When Epclusa was given with ribavirin, common side effects included fatigue, headache, anemia, nausea, insomnia and diarrhea.
Serious slowing of the heart rate (bradycardia) may occur when amiodarone (brand names Cordarone, Pacerone, Nexterone), a medicine used to treat heart problems, is taken with Epclusa. In some cases bradycardia has led to death or the need for a heart pacemaker when amiodarone is taken with medications similar to Epclusa that are a combination of sofosbuvir and another antiviral drug.
There are other medications that should not be taken with Epclusa – including prescription, over-the-counter medicines, and herbal supplements – so tell your healthcare provider about all the medicines you take before starting Epclusa.
It’s a very exciting and hopeful time for people with Hepatitis C as treatment is rapidly changing for the better. We now have higher cure rates, shorter treatment times, and oral treatment regimens for all people with HCV infection. For current treatment protocols, please see “Medication Regimens According to HCV Genotype.”
This page has been updated and medically reviewed October 2016.