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New Hepatitis C Drug Receives FDA Approval

By: Ada Seldin, Staff Editor

On November 22, 2013, simeprevir (Olysio®), a new agent to treat chronic hepatitis C, received approval under the FDA’s priority review program. Simeprevir is an NS3/4A protease inhibitor that blocks the replication of the hepatitis C virus. Two other drugs from the same class, boceprevir and telaprevir, which were approved in 2011, drastically improved treatment outcomes for patients with chronic hepatitis C virus infection.1 All three of these protease inhibitors are indicated as a part of an antiviral regimen in combination with pegylated interferon and ribavirin in adults infected with genotype 1 hepatitis C virus with compensated liver disease, including cirrhosis. They have been shown to be effective in both treatment naïve and treatment-experienced patients who have either relapsed, failed prior therapy, or had only partial response to prior therapy.2 Genotype 1 is the most treatment-resistant of the hepatitis C viruses and is, unfortunately, also the most common type in the U.S. Thus, simeprevir will play an integral role in the treatment of hepatitis C.

Hepatitis is an inflammatory disease of the liver that results in liver cell death. Although it is most commonly caused by a viral infection, drugs or toxins can also precipitate hepatitis C. The five main hepatitis viruses that are responsible for significant human disease are: A, B, C, D, and E. Hepatitis C is particularly devastating for many reasons. Newly infected patients are often asymptomatic or present with mild, nonspecific symptoms and are thus unaware of their condition, thereby increasing the risk of transmission. Furthermore, 70-85% of HCV-infected patients will develop chronic disease, which can lead to cirrhosis and liver cancer.  Unfortunately, there is no vaccine to date for the prevention of hepatitis C infection. Because HCV is a blood-borne pathogen, prevention consists of behavioral precautions, such as barrier contraception as well as avoiding the sharing of syringes. Thanks to effective screening protocols, blood transfusions are no longer a major source of infection. Nonetheless, 3.2 million Americans are living with chronic hepatitis C. Injection drug use is by far the leading risk factor for infection. Perinatal and sexual transmission is also possible, but occurs less frequently. Finally, hepatitis C virus has at least six genotypes, which complicates treatment and exposes the patient to reinfection with different strains.3

The goal of drug therapy is to achieve undetectable viral load 12 to 24 weeks after completion of therapy. This is known as SVR, sustained virologic response. Combination therapy with simeprevir, pegylated interferon, and ribavirin exhibits marked superiority over pegylated interferon, ribavirin, and placebo according to the results of three Phase 3 studies known as QUEST-1, QUEST-2, and PROMISE. The QUEST trials studied treatment-naïve patients and PROMISE studied patients who relapsed after prior interferon-based treatment.  Based upon the data from the QUEST studies, 80% of treatment-naïve patients achieved sustained virologic response 12 weeks after combination treatment with simeprevir, while only 50% of the placebo controlled group had SVR. Similarly, 79% of patients randomized to the simeprevir group in the PROMISE study had SVR at 12 weeks, while 37%of patients in the placebo group achieved such results.5 ASPIRE, a Phase 2b study, demonstrated that the addition of simeprevir to the pegylated interferon/ribavirin regimen led to a sustained virologic response after 24 weeks in 65% of prior partial responders and 53% of prior non-responders versus 9%and 19% of the respective placebo groups. 6 Interestingly, simeprevir was not compared in head-to-head trials with the other protease inhibitors on the market.

Simeprevir offers the unique advantage of once daily dosing.7,8 This will reduce pill burden and may improve compliance. The most common side effects seen in clinical trials include rash, pruritus, photosensitivity, and nausea. Patients should be instructed to avoid extensive sun exposure and to protect themselves with sunscreen, hats, and clothing. Telaprevir shares a similar side effect profile. Like its protease inhibitor predecessors, simeprevir is metabolized primarily by CYP P450 3A4, and is therefore susceptible to drug interactions with potent inhibitors or inducers of this enzyme.  Since ribavirin is pregnancy category X and simeprevir is only indicated for combination therapy, all males and females taking this drug must use two forms of birth control. It is unknown whether simeprevir passes into breast milk. Patients with decompensated liver disease should not take simeprevir. In addition, it is recommended to screen patients for NS3 Q80K polymorphism in genotype 1a virus, as a reduction in efficacy is observed in this population.9

      Evidence suggests that simeprevir is safe and effective for its intended use. It has the potential to substantially reduce morbidity and mortality in millions of Americans. However, its place in therapy among other protease inhibitors used in combination with pegylated interferon and ribavirin remains to be seen.


  1. U.S Department of Health and Human Services. FDA approves new treatment for hepatitis C virus. U.S Food and Drug Administration. Published November 22, 2013. Accessed January 4, 2014.
  2. Janssen Therapeutics. Olysio (simeprevir) receives FDA approval for combination treatment of chronic hepatitis C. Johnson & Johnson.ƒc-Hepatitis-C. Last updated November 25, 2013. Accessed January 4, 2014.
  3. CDC. Hepatitis C information for health professionals. Centers for Disease Control and Prevention. Last update May 7, 2013. Accessed January 4, 2014.
  4. Fred Poordad, Michael P. Manns, Patrick Marcellin, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype-1 infection in treatment-naive patients: results from QUEST-2, a phase III trial. Gastroenterology Vol. 144, Issue 5, Supplement 1, Page S-151
  5. Eric Lawitz, Xavier Forns, Stefan Zeuzem, et al. Simeprevir (TMC435) with peginterferon/ribavirin for treatment of chronic HCV genotype 1 infection in patients who relapsed after previous interferon-based therapy: results from PROMISE, a phase III trial. Gastroenterology Vol. 144, Issue 5, Supplement 1, Page S-151
  6. Stefan Zeuzem, Thomas Berg, Edward Gane et al. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology 2013 S0016-5085(13)01576-X
  7. Victrelis full prescribing information. Merk & Co. Inc. Last updated February 2013. Accessed January 4, 2014.
  8. Incivek full prescribing information. FDA website. Last updated December 2012. Accessed January 4, 2014.
  9. Olysio full prescribing information. Janssen Therapeutics. Last updated November 2013. Accessed January 4, 2014.
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