The High Price of the New Hepatitis C Virus Drugs
Authors: Robert Steinbrook, Rita F. Redberg
Journal: JAMA Internal Medicine (2014)

Although the development of effective, oral medications for chronic hepatitis C virus infection (HCV) is a scientific triumph, the high price of the newest, directly acting antiviral agents, simeprevir and sofosbuvir, has sparked a muchneeded debate about the fair pricingofpharmaceuticals. In theUnitedStates, thecosts for 12 weeks of therapy, for the drugs alone, can range from$66 360 for simeprevir to $84 000 for sofosbuvir, or $1000 per tablet of the latter medication.1 In this issue of JAMA Internal Medicine, Ollendorf et al,1 at the Institute for Clinical and Economic Review, summarize their reviewof the evidence about the comparative effectivenessandeconomic impactof simeprevir andsofosbuvir.2Their analysis reveals “a stark dilemma: the advent of newdrugs of tremendous potential to treatmillions of patientswho have a serious liver infection—but at a price that the health care system in theUnitedStatesmay findunaffordable.”1 In theUnited States, an estimated 3.2million persons have chronicHCV infection, and about 15 000people die from the infection annually,primarily fromliver failureandhepatocellular carcinoma.3 Globally, theWorldHealthOrganization (WHO)estimates that 130 to 150millionpeople have chronicHCV infection and that 350 000to500 000peopledieeachyear fromHCV-related liver diseases.4 There is no precedent for drugs with such apparent public healthbenefits for somanypeople to bepriced at suchhigh levels. As theWHOnoted inApril 2014,when it issued its first HCV treatment guidelines: “Although the production cost of DAAs [directly acting antiviral agents] is low, the initial prices set by companies are very high and likely to make access to thesedrugsdifficult even inhigh-incomecountries.”4Thecost of treating chronic HCV infection is set to increase by untold billions of dollars a year. Already, sales of sofosbuvir,which is marketedbyGileadasSolvadi,were$2.3billion in the first three months of 2014, an apparent record for sales of a drug in its first full quarter of marketing.5 In theUnitedStates,pharmaceutical companieshavewide latitude to set thepriceofmedications,which factor in thesubstantial costs of researchanddevelopmentofnewagentsprior tomarketing approval. Nonetheless, there is a disturbing disconnection between the very high initial prices set by companiesandthe relatively lowmanufacturingcosts.A recentanalysis applied lessons learned from the progressive decrease in the manufacturing costs of HIV medications to estimate the minimumproduction costs of directly acting antiviral agents for HCV.6 The ranges of predicted manufacturing costs were $68 to$136 for a 12-weekcourseof sofosbuvir, and$130 to$270 for a 12-week course of simeprevir. Even if the assumptions in this analysis were insufficiently conservative, the gap between the estimatedmanufacturing costs of these drugs and their pricing in the United States would still be striking. At current projections, the cost of directly acting antiviral agents for HCV is likely to quickly overwhelm the budgets of any stateMedicaidprogramor anyprivate insurer. Thesehigh costs are of particular concern because these drugs were approved quickly based on the surrogate end point of sustained virologic response rate; they were studied in limited populationsandwithout long-termfollow-up.Under theUSFoodand DrugAdministration’s breakthrough therapydesignation, the marketing approval for sofosbuvir did not include requirements for randomized clinical trials. Company-sponsored, direct-to-consumer advertising campaigns to encourage HCV testing in healthy persons are already in full swing. A national discussion is urgently needed of the appropriate continuedevidence collectionandpricing for thenewHCVdrugs, andwhether their use shouldbe restricted topatientswith advanced liver disease. The evidence report by Ollendorf et al,1 additional data from clinical trials, and forthcoming evidence reports will provide the basis for that discussion.