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 (RBV)
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:
- Boceprevir (brand name VICTRELIS)
- Telaprevir (brand name INCIVEK)
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:
- Simeprevir (brand name OLYSIO)
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 (brand name SOVALDI)
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:
- Ledipasvir/sofosbuvir (brand name HARVONI)
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.
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):
- Ombitasvir/paritaprevir/ritonavir tablets; dasabuvir tablets (brand name VIEKIRA PAK)
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 1a and 1b, including people new and experienced to treatment, and people with compensated cirrhosis.
The FDA approved two new drugs – TECHNIVIE for the treatment of HCV genotype 4 and DAKLINZA for the treatment of HCV genotype 3.
- Ombitasvir/paritaprevir/ritonavir (brand name TECHNIVIE)
Technivie was approved for use in combination with ribavirin for the treatment of HCV genotype 4 in patients without scarring and cirrhosis. This is 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 (brand name DAKLINZA)
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. Co-administration of amiodarone with sofosbuvir in combination with Daklinza, is not recommended.
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 all-oral treatment regimens for most people with HCV infection. For current treatment protocols, please see “Medication Regimens According to HCV Genotype.”
This page has been updated and medically reviewed September 2015.