Published Online: March 31, 2014
Gary M. Owens, MD
Hepatitis C (HCV) is an infectious disease that generally causes only mild or no symptoms initially, but the virus quickly goes on to reside in the liver of about 85% of people who get infected. Chronic HCV can lead to scarring of the liver and ultimately to cirrhosis, which may only become apparent after many years. In some cases, those with cirrhosis will also develop liver failure or liver cancer.
It is estimated that 150 to 200 million people, or about 3% of the world's population, are living with chronic HCV. About 3 to 4 million people are infected per year, and more than 350,000 people die yearly from HCV-related diseases. In 2010, an estimated 196,000 deaths occurred from liver cancer secondary to the HCV infection.1
In the United States, there are approximately 3.2 million people with chronic HCV infection. Interestingly, the baby boomers—those born between 1945 and 1965—represent the largest segment of the US population with this infection, the majority of whom were likely infected during the 1970s and 1980s when rates were highest.2
As can be seen in the graphic to the left, a substantial number of individuals will develop liver disease from chronic HCV infection. It is generally difficult to predict who will ultimately go on and develop severe complications, therefore current recommendations are that those with the disease should be treated in an attempt to eradicate the infection. If not treated, some patients will develop cirrhosis or liver cancer and may require a liver transplant. HCV is the leading reason for liver transplantation, though the virus usually recurs after transplantation and requires further treatment.
Standard therapy for HCV infection has typically been a combination of peginterferon alfa and ribavirin, with either boceprevir or telaprevir added in some cases. Overall, 50% to 80% of people treated with a 3-drug regimen are currently cured. However, these drug regimens have significant side effects and for some patients, the duration of treatment approaches 1 year. It is also important to note that there are 6 genotypes of HCV, and the intensity and duration, as well as treatment success rates, vary by genotype.
The first of 2 new HCV treatments—simeprevir (Olysio) was approved on November 22, 2013, by the US Food and Drug Administration (FDA). This drug is an oral agent that is intended to be used as part of a combination regimen for the treatment of chronic HCV infection in adults, including patients with compensated cirrhosis or other stable liver disease. Simeprevir is indicated, in combination with peginterferon alfa and ribavirin, for the treatment of infections caused by HCV genotype 1, according to the drug's labeling.3
In 1 clinical trial, the addition of simeprevir to the treatment regimen resulted in up to 80% of trial participants with genotype 1 HCV infection becoming free of infection after completing their treatment.3
Genotype 1 infections are more difficult to threat than some other genotypes, and the results of the clinical trials were considered a significant advance.
On December 6, 2013, sofosbuvir (Sovaldi) was approved by the FDA. Sofosbuvir—an oral therapy, taken as tablets—is used as part of a regimen for the treatment of chronic HCV infection caused by viruses of genotypes 1, 2, 3, or 4.
According to the FDA, sofosbuvir is the first drug that can be used without an interferon product to treat certain types of chronic HCV infection. According to the label, sofosbuvir may be used in any of the following ways:
Newer HCV Treatments Are Expensive
For patients infected with HCV of genotype 1 or 4, the recommended treatment regimen is 12 weeks of triple therapy with sofosbuvir, peginterferon alfa, and ribavirin. The labeling also recommends 24 weeks of dual therapy in patients with genotype 1 infection who cannot take interferon.
For patients with HCV genotype 2 infection, a 12 weeks of dual therapy with sofosbuvir and ribavirin is recommended.
For patients with HCV genotype 3 infection, 24 weeks of the dual therapy with ribavirin is recommended.
Advances in therapy are expected to command price increases, however many health plans and pharmacy benefit managers (PBMs) have questioned the pricing of these 2 new agents. Janssen has set the wholesale acquisition cost (WAC) for a single 12-week course of simeprevir at $66,360. Although the price is similar to current HCV drugs in this class (telaprevir and boceprevir), this price represents only part of the cost of treatment, which also includes at least $18,000 in WAC costs over 12 weeks for interferon and ribavirin, plus the additional cost of laboratory monitoring and screening tests.
Gilead’s sofosbuvir came to market at an even higher WAC price. According to the New York Times, the pill has a projected WAC of $28,000 for a 4-week treatment, or $1,000 per daily pill. That translates to $84,000 for the 12-week treatment cycle recommended for most patients, and $168,000 for the 24 weeks needed for a hard-to-treat strain of the virus. Also from the same article: “Some analysts expect Sovaldi to become one of the best-selling drugs in the world. Matthew Roden, an analyst at UBS, said in a note on Friday that annual sales could surpass the record of around $13 billion achieved by Lipitor, from Pfizer, in its peak year.”5
These 2 new agents are just the beginning of a new era in HCV treatment that will hopefully result in better cure rates, reduced side effects, and all-oral treatments for the majority of patients. AbbVie, Bristol-Myers Squibb, Merck, Johnson & Johnson, and others are also developing all-oral regimens for HCV that could reach the market in the next 1 to 3 years.5
With pricing for these agents reaching unprecedented levels for HCV treatment, considerable controversy has arisen. For instance, Express Scripts has stated that it wants drug makers to compete for formulary inclusion of new HCV drugs. "We will identify which drugs can be pitted against each other and make some really tough formulary decisions," said Express Scripts chief medical officer Steven Miller. The PBM will recommend coverage of the least expensive drug in the absence of data demonstrating a difference in outcomes.6
Likewise, a more convenient dosing schedule may not be enough to get preferred reimbursement, Miller said, especially with the high prices. “If a company is just relying on a convenience factor to get that product covered, they may end up being disappointed,” he said.6
The cost for treating HCV patients is almost certainly going to increase in 2014. At the present time, payers are considering the following strategies for managing the class:
Prior authorization of all agents in the class
Monitoring duration and response to therapy according to genotype
Monitoring for potential combinations of therapies that are not supported by the FDA-approved labeling or by available published data
Potential limited first fill programs to ensure patient tolerance and responsiveness to therapy
Limitations on duration of therapy according to FDA labels
Selection of preferred agents where clinically appropriate
Aggressive negotiation for pricing concessions to gain preferred therapy status
It will be interesting to see how the treatment of this severe illness will evolve in 2014 and beyond. Meanwhile, payers will struggle to strike a balance between the need for improved clinical outcomes, proper patient selection, and effective management of cost in the class.
Hepatitis C. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs164/en/index.html. Updated July 2013. Accessed December 15, 2013.
Hepatitis C information for health professionals. Centers for Disease Control and Prevention website. http://www.cdc.gov/hepatitis/HCV/HCVfaq.htm#section1. Updated February 10, 2014. Accessed December 12, 2013.
Traynor K. Simeprevir approved for hepatitis C virus infection. American Society of Health-System Pharmacists website. http://www.ashp.org/menu/News/PharmacyNews/NewsArticle.aspx?id=3988. Published November 25, 2013. Accessed December 17, 2013.
Traynor K. Sofosbuvir approved for chronic hepatitis C infection. American Society of Health-System Pharmacists website. http://www.ashp.org/menu/News/PharmacyNews/NewsArticle.aspx?id=3993. Published December 9, 2013. Accessed December 17, 2013.
Pollack A. FDA approves new pill to treat hepatitis C. New York Times. December 8, 2013. http://www.nytimes.com/2013/12/07/business/fda-approves-pill-to-treat-hepatitis-c.html. Accessed December 17, 2013.
Express Scripts pushes price competition for Gilead drug. Bloomberg News website. http://www.bloomberg.com/news/2013-12-10/express-scripts-pushes-price-competition-for-gilead-drug.html. Published December 10, 2013. Accessed December 17, 2013.