The Federal Drug Administration of the US approves new drugs solely on the basis of safety and effectiveness, with no value assessment. Pharmaceutical companies mayÂ set their drug prices based mainly on what the market will bear. Nevertheless, the announcement thatÂ Gilead Sciences would priceÂ their just-approved, anti-hepatitis C virus (HCV) drug sofosbuvir (Solvaldi) atÂ $84,000 for 12 weeks of treatment was met with considerable complaints.
Solvaldi is a member of a class of antiviral drugs called nucleoside analogs. They act as chain terminators and inhibit viralÂ RNA synthesis. When the viral RNA polymerase is copying the viral RNA, to enable the production ofÂ more virus particles, it normally uses the pool of ATP, UTP, GTP, and CTP to produce more RNA. When Solvaldi is incorporated into the growing RNA chain by the viral enzyme, no additional triphosphates can be added, because the drug contains a fluorine atomÂ at the 2′-position of the ribose. ItsÂ presence inhibits addition of the next nucleoside by the polymerase to the 3′-OH. Viral RNA synthesis therefore stops, and production of virus particles is inhibited. For more information on chain terminators, see my virology lecture on antivirals.
Gilead believes thatÂ the price of the drug isÂ fully justified: a spokesperson saidÂ “We’re just looking at what we think was a fair price for the value that we’re bringing into the health care system and to the patients.”
It could cost up to $300,000 to treat patients with chronic HCV infection using less effective and more difficult to tolerate regimens. The potential benefit of a cure for patients with liver disease is clear, as the virus is the main reason that nearly 17,000 Americans are waiting for a liver transplant. The need for a well-tolerated, effective regimen is equally critical for people infected with HIV and HCV, because having both infections accelerates liver damage.
Despite these arguments, the high price will be a significant barrier for many, especiallyÂ those in limited and fixed-budget programs such as Medicare and Medicaid. AÂ panel of experts in San Francisco estimated that switchingÂ HCV infected Californians toÂ Sovaldi would raise annual drug expenditures in the state by at least $18 billion.
Gilead has agreed to help U.S. patients pay for Sovaldi if they cannotÂ afford it, or help patients obtainÂ drug coverage. The company also plans toÂ charge substantially less for a course of treatment in India ($2000 for the 12 week course), Pakistan, Egypt ($990 for the 12 week course), and China, where most people infected with HCV live. These deals have prompted some to ask if the US isÂ being forced to subsidize the cost of the drug worldwide. I personallyÂ do not object to helping other countries solve their HCV problem.
What is a fair price for a drug that can eliminate HCV infection? Gilead paid more than $11 billion in 2011 to acquire the company that developed Sovaldi, and it is reasonable for them to recoup that investment. Andrew Hill of the Department of Pharmacology and Therapeutics at Liverpool University estimates the manufacturing cost of a 12 week course of treatment with this drug to be $150 to $250 per person. The answer to our fair price question must lieÂ somewhere between these extremes.
There are parallels between Sovaldi (and other new anti-HCV drugs in the pipeline) and the initially expensive antivirals that were introduced ~20 years ago to treat HIV. Anti-retroviralsÂ revolutionized the treatment of a chronic, lethal infection that isÂ major global health problem, and the anti-HCV drugs could have the same effect. But there are also important differences: based on the number of infected individuals,Â HCV is a much larger public health threat than HIV. Furthermore, the new HCV antivirals can eliminate the virus completely, whereas anti-HIV drugs only suppress virus replication, so they must be taken (and paid for) for life.
At some point in the future competition among pharmaceutical companiesÂ andÂ manufacturers of generic drugs should make it possible to treat everyone infected with HCV with affordable, curative antivirals. If the cost and efficiency of diagnosis and drug delivery keeps pace, it might be possible to eradicate HCV. That accomplishment might well be priceless.