Incivek and Victrelis, approved for Hepatitis C within weeks of each other in May 2011, look to change the way the disease is treated.
Hepatitis C is a viral disease that causes infl ammation and swelling of the liver, which can lead to diminished function or failure of the organ over time. Most people who are infected are unaware that they have the disease because it is frequently asymptomatic until liver damage occurs, often years after initial exposure to the virus. The disease is the leading cause of liver transplants in the United States.1 Hepatitis develops initially as an acute infection. Of those persons with acute infection, perhaps one-fourth will generate an immunologic response sufficient to clear the virus; the remaining three-fourths cannot do so, resulting in chronic hepatitis C virus (HCV) infection.2 According to the US Centers for Disease Control and Prevention, about 3.2 million Americans have chronic HCV.3
Many chronic HCV patients are waiting for a new therapy option. This group includes those who are poor candidates for initiation of treatment with the existing standard of care for any one of several reasons, as well as those nonresponders who failed to achieve sustained virologic response (SVR) following their initial treatment.2
In May 2011, the US Food and Drug Administration approved 2 new competing oral protease inhibitors, Vertex Pharmaceuticals’ Incivek (telaprevir) and Merck & Company’s Victrelis (boceprevir), to treat adults with chronic HCV infection who are either treatment naïve or who did not respond to drug therapy. Both Incivek and Victrelis are dosed 3 times daily, and are approved for adjunctive use with pegylated interferon and ribavirin.1,3
Until recently (May 2011), the standard of care for most patients with chronic HCV was a combination of injectable pegylated interferon and oral ribavirin taken for 48 weeks, the goal of which is an SVR, or a suppression of the virus to undetectable levels for at least 24 weeks following the cessation of therapy.4 Achievement of SVR suggests that the virus has been eradicated. The purpose of treating the infection is to reduce the risk of developing long-term complications such as cirrhosis and hepatocellular carcinoma, and to reduce the mortality rate associated with the disease.1
The treatment rate for chronic HCV is very low; it is estimated that fewer than one-fourth of chronically infected individuals have been treated. This low treatment rate is partly because many patients with HCV go undiagnosed, but it is also because of insuffi cient infl ammatory activity to merit therapy and the harshness of the interferon regimen.2 Of those patients who do receive the existing standard of care, fewer than 50% respond.1
The stated benefit of these 2 new drugs is that they may increase the likelihood of treatment success for patients with genotype 1 hepatitis C infection.4 The 3-drug regimen (pegylated interferon plus ribavirin plus either Victrelis or Incivek) signifi cantly increases the likelihood of an SVR for patients with genotype 1. The SVR rates with Incivek and Victrelis therapy cannot be directly compared because there have been no head-to-head trials of these agents. However, the SVR rates for the new protease inhibitors are very similar overall.4 Additionally, patients with a good response to the combination HCV regimen containing a protease inhibitor may have a potentially shorter duration of HCV therapy.5,6
Our objectives were to determine what percentage of members receiving therapy for HCV are taking Incivek or Victrelis and to outline the demographic characteristics of these members.
In a retrospective analysis of the CVS Caremark book of business, which represents approximately 41 million members, it was determined that as of September 2011, there were 3151 unique utilizers of HCV therapy. Of those unique utilizers, 46.14% had a regimen containing a protease inhibitor (ie, Incivek or Victrelis) for the treatment of HCV; 257 were taking Victrelis therapy and 1197 were taking Incivek (both agents were being taken in addition to a standard HCV regimen).
outlines the demographics of members on Incivek or Victrelis therapy. Of the unique utilizers receiving therapy for HCV, 37.99% were on Incivek therapy and 8.16% were on Victrelis therapy. Of the 1454 members on a protease inhibitor for HCV, 17.68% were on Victrelis therapy and 82.32% were on Incivek therapy.
Following approval of Victrelis on May 13, 2011, Merck said that it would be launched to pharmacies within a week at a wholesale acquisition cost (WAC) of $1100 per week,7 dosed for 24 to 44 weeks, while Vertex said that Incivek would carry a WAC of $49,200 for a 12-week course of therapy.8 The WAC for Incivek will be only $800 higher for the course of therapy than the WAC for Victrelis patients who take that drug for 44 weeks. But for Victrelis patients who receive the drug for 24 weeks, the cost will be less than that for Incivek. The duration of treatment with Victrelis, however, is not determined until after starting treatment. Both agents produce a substantially greater SVR rate than that produced by the existing standard of care. Although Incivek and Victrelis have not been tested against each other in a head-to-head study, Incivek produced an SVR rate of 79% in treatment-naïve patients during a phase III trial, compared with 46% for the existing standard of care; and Victrelis produced SVR rates between 63% and 66% in treatment-naïve patients.8
Merck also announced that Victrelis would be copromoted by Roche. Merck and Roche are the current market leaders in HCV treatments, with Merck selling PEG-Intron (pegylated interferon alfa 2b) and Rebetol (ribavirin), and Roche marketing Pegasys (pegylated interferon alfa 2A) and Copegus (ribavirin). In addition to the Merck and Roche branded versions, ribavirin also is available in generic form.9
Incivek, however, was approved with labeling advantages that have enabled it to win a majority of the available market versus Victrelis.10 Incivek received a label that will enable an estimated 60% of patients (treatment-naïve and prior relapsers who achieved early rapid viral response) to receive the drug under a response-guided therapy regimen. A response-guided therapy regimen entails a 12- week course of Incivek plus the existing standard of care (pegylated interferon [which is self-injected once weekly during the treatment period] and ribavirin [an oral pill taken twice daily during the treatment period]),4 followed by another 12 weeks on standard of care. Patients who don’t qualify for that regimen will receive Incivek for 12 weeks with the standard of care, followed by another 36 weeks on standard of care alone.10
Cost-Effectiveness Study Supports Limiting Incivek Use
A recent cost-effectiveness study conducted by Duke University researchers could support the limitation of first-line use of Incivek to those HCV patients who stand to benefi t the most, based on genetic testing.11 The study suggests that treatment-naïve genotype 1 patients who have the CC type IL28B polymorphism would do just as well on the existing standard-of-care treatment (pegylated interferon/ribavirin), which costs far less than either Incivek or Victrelis. Study results show that those with the CC type IL28B polymorphism respond well to standard of care, whereas those with the TT type tend to respond poorly and those with the CT type have a mixed response. About 65% of patients have either the TT or CT alleles. The existing standard-of-care treatment costs from $18,000 to $36,000, researchers noted; adding Incivek increases the cost to between $67,000 and $85,000, while adding Victrelis results in a total cost ranging from $47,000 to $71,000.11
Leading up to the approval and launch of Victrelis and Incivek, some market analysts predicted that Incivek could outsell Victrelis on the basis of superior effi cacy and a shorter duration of therapy for many patients.12 The actual inequality in third-quarter sales of the 2 drugs has been surprising, however, as Incivek posted net sales of $420 million for the quarter while Victrelis recorded just $31 million in sales.13
Vertex said that between 60% and 70% of Incivek prescriptions have been written for patients new to therapy, with the remainder going to patients who avoided the existing standard of care due to the length of therapy and severity of side effects.12 Merck noted that Victrelis is the only protease inhibitor for HCV listed on the Veterans Administration (VA) formulary, and that with 130,000 patients, the VA is the largest single healthcare provider for HCV patients in the country. The VA doctors also can prescribe Incivek for their patients, but under a more complicated, paperwork-intensive process.12
Vertex hopes to offset the high price of Incivek by providing it at no cost to uninsured patients with household incomes up to $100,000, through copay assistance for patients with private insurance, and through indirect copay assistance for government-insured patients.8 Its copay assistance program will cover up to 20% of Incivek’s cost for patients with insurance plans that cover Incivek, regardless of income. To help patients covered through government programs or living in Massachusetts (where copay assistance limitations apply), Vertex will make donations to the nonprofit Patient Access Network Foundation, which has a fund to provide copay support for patients on HCV therapy.8 The company expects about 60% of patients to be covered by private insurance and 35% to have government coverage. Merck also offers a copay assistance program for Victrelis, offering patients a discount card that provides assistance of up to $200 off on up to 12 prescriptions of the drug.8
The extent to which copay assistance may have an impact on product uptake and market share is diffi cult to gauge. Claims data indicate that a copay has been paid, but not who has paid it. Companies can only suspect coupon use when generic dispensing declines substantially or there is a spike in claims for certain brands.14
There is a very active pipeline for HCV therapy. Selected drugs/indications in phase III trials include the following15:
• Incivek is in phase III trials for the treatment of genotype 1 chronic HCV in patients with the CC variation near the IL28B gene; approval for this supplemental indication may occur in 2014 if trial results are positive.
• PSI7977 is a DNA polymerase inhibitor in phase III trials for the treatment of HCV infection in combination with ribavirin. If approved, this agent is anticipated to launch in the second half of 2014.
• BI201335 is a protease inhibitor in phase III trials for the treatment of chronic HCV infection in combination with pegylated interferon-alfa 2a and ribavirin. If approved, this agent is anticipated to be available in 2015.
• Simeprevir is in phase III trials for the treatment of genotype 1 chronic HCV in combination with pegylated interferon and ribavirin. If approved, this agent is anticipated to become available in 2014.
Of the patients currently taking a regimen for the treatment of HCV, 46.14% were being treated with either Incivek or Victrelis. A larger percentage (82.32%) of members on HCV therapy containing a protease inhibitor were reasons for this are not entirely clear, Incivek’s more rapid uptake could have to do with a perception of superior efficacy coupled with its approval for use in a response-guided therapy regimen. The strong uptake of both agents in a short period of time is an indicator that this disease state is primed for new therapeutic options. The active pipeline for the treatment of HCV will have an impact on trend for a number of years to come.