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The Price of a Cure
DAA is $1,000 a pill; SVR is priceless.
The new generation of direct-acting antiviral agents for the treatment of hepatitis C virus promise a potential cure for an estimated 3 million infected Americans, but also promise to come with a high price.
The therapies are making headlines in both the health care community and the mainstream media, largely for three reasons: the drugs’ unprecedented efficacy, attractive adverse event profiles and cost. Although recently approved drugs such as sofosbuvir (Sovaldi, Gilead Sciences) and simeprevir (Olysio, Janssen Therapeutics) have been hailed as groundbreaking therapies with high sustained virologic response rates, the costs are under scrutiny.
Nancy S. Reau
Gilead Sciences announced that the price of sofosbuvir is $1,000 per pill, which equates to $84,000 for a 12-week treatment course. Given that the drug may be administered with companion drugs and the HCV mainstays interferon and/or ribavirin, the cost per cure may exceed six figures. Moreover, some patients may require 24 weeks of treatment at double the cost. Simeprevir has been priced at $66,000 for a course of treatment, excluding the cost of other therapies, including when combined with sofosbuvir. Cost will likely remain a hot topic, with a number of other direct-acting antivirals (DAAs) and combinations in the pipeline and nearing approval. After more than 2 decades of moderately effective, poorly tolerated interferon-based treatment options, the drug companies hold most, if not all, of the cards.
However, the price tag leaves many questioning who will get access to the new drugs, and when. Some experts said the costs render these drugs inaccessible for the many patients with HCV, whereas others said the costs are justified.
Donald M. Jensen
HCV Next spoke with a cross-section of experts about how to navigate the cost per cure.
Hard Numbers
It is important to frame the discussion in the context of the economic burden of HCV against the retail cost of new therapies, HCV Next Editorial Board member Nancy S. Reau, MD, and Donald M. Jensen, MD, from the Center for Liver Disease at University of Chicago Medicine, wrote in an April issue of Hepatology.
According to Geoffrey M. Dusheiko, MD, emeritus professor of medicine at the University College of London Institute of Liver and Digestive Health at Royal Free Hospital, HCV treatment has always been expensive. “It already costs quite a bit to cure someone of HCV,” he told HCV Next.
Geoffrey M.
Dusheiko
A recent study by Gordon and colleagues compared the economic burden for US patients with chronic HCV (n=53,796) stratified by severity of liver disease in a large private health insurance claims database from 2003 to 2010. The annual health care costs of chronic HCV were estimated to be $24,176. When examined by disease stage, average annual costs were estimated to be $17,277 for patients with no cirrhosis, $22,752 for patients with compensated cirrhosis and $59,995 for patients with end-stage liver disease. As patients with compensated cirrhosis may live for more than a decade, costs may rise to $270,000 before developing end-stage liver disease, according to this model. Other estimates from the United Network for Organ Sharing’s Transplant Living website suggest that the average of billed charges per liver transplant was $577,100 in 2011.
“We didn’t realize how much we were spending because payers did not aggregate all of the costs associated with treatment,” Camilla S. Graham, MD, MPH, from the division of infectious diseases at Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, said in an interview.
Graham cited data from Sethi and colleagues, who reported that regimens with some combination of interferon, ribavirin, telaprevir (Incivek, Vertex) or boceprevir (Victrelis, Merck) cost more than $164,000 among relapsed patients, more than $260,000 for those with cirrhosis and more than $300,000 in partial or null responders.
Camilla S. Graham
“HCV therapy has evolved from standard interferon-alfa for 24 weeks, which offered a 6% SVR rate and would cost less than $20,000 today, to peginterferon and ribavirin for 48 weeks, with SVR rates increasing to 40% to 60%, but also with double the price. With the approval in 2011 of HCV protease inhibitor direct-acting antivirals, efficacy improved, but the cost increased substantially to over $70,000. When the total cost of therapy to achieve SVR is considered, including management of complications, the price of treatment actually increases to $172,889 to $188,859 per SVR,” Reau and Jensen wrote in their editorial.
Treatment cost per SVR may be more reasonable to estimate the cost impact of new therapies, according to Reau and Jensen. “Cost is important, but effective, safe therapy is paramount. … Although DAA therapy may be $1,000 a pill, SVR is arguably priceless,” they wrote.
Hagan et al conducted a cost-effectiveness study comparing interferon-based standard of care with all-oral, interferon-free regimens. Across a range of willingness-to-pay thresholds, the incremental cost-effectiveness ratio for the oral regimens was $44,514 per quality-adjusted life year (QALY). “All-oral treatment was most cost-effective among genotype 1 subjects, but remained cost-effective for genotypes 2 and 3 at [willingness-to-pay] thresholds ≥$80,000/QALY,” they wrote in the Journal of Viral Hepatitis.
Few hard data are yet available for costs of the new treatments. Rather, there is a lot of speculation. For example, a recent panel of experts in California in March voted that sofosbuvir represents a “low value” treatment as compared with older drugs. In addition, the California Technology Assessment Forum estimated that sofosbuvir may raise annual drug costs in that state by $18 billion to $29 billion. The group voted, however, that the new therapies are superior to the old therapies. The panel is expected to conduct similar analyses for simeprevir and other drugs in the pipeline.
Andrew M. Hill, PhD, from the department of pharmacology and therapeutics at Liverpool University in the United Kingdom, provided his opinion on a larger scale. “If all 3 million people infected with HCV in the United States were treated with [the currently approved DAAs] at a cost of $150,000 each, the cost would be $450 𠊋illion, not including diagnostic support or medical care costs.”
Hill said these numbers are particularly high in light of the costs to produce the drugs. He and colleagues conducted a study to determine minimum manufacturing costs per gram of antiretrovirals. “Predicted manufacturing costs (US dollars) for 12-week courses of HCV DAAs were … $68-$136 for sofosbuvir … and $130-$270 for simeprevir,” they wrote in Clinical Infectious Diseases.
Cost Per Cure
Given that the new drugs can eliminate HCV, Graham said the high cost might be justified. In addition, “there are not as many costs associated with administering these regimens,” she said, referring to sofosbuvir-containing treatment courses as well as some of the other combinations under investigation. “On the surface, these new regimens appear expensive, but when you look at the cost per cure they may be much less expensive because there are so few other costs.” She said payers should consider the cost per cure as well.
Ryan Clary, executive director at the National Viral Hepatitis Roundtable, �ressed the issue in different terms. “The cost of not treating patients is obviously higher than $84,000, for example,” he said, citing liver transplantation, cancer and end-stage disease as consequences of failure to treat.
Michael W. Fried, MD, professor of medicine and director of the University of North Carolina Liver Center, added to this point. “From a patient perspective, the costs may not appear so great because they know there is a high likelihood of being cured. They won’t have to deal with those complications for the rest of their lives. They can move on and put HCV behind them �use even when they are asymptomatic, it is still impacting them. We should not lose sight of that.”
HCV Next contacted Gilead Sciences for comment. “The cost of the entire HCV regimen of 12 weeks of Sovaldi with interferon and ribavirin is consistent with and, in many cases, actually less than the cost of the previous protease inhibitor-based regimens — with shorter duration of therapy, increased tolerability and higher efficacy,” a company spokesperson said. “Further underscoring the value of Sovaldi, the American Association for the Study of Liver Diseases/Infectious Diseases Society of America HCV guidelines, which were updated rapidly after the FDA approval of Sovaldi, now recommend it as a preferred HCV treatment across multiple patient populations.”
Janssen Therapeutics did not respond to requests for comment.
Downstream Complications
The novel therapies are associated with a lower cost per cure because they are associated with reductions in the risk for serious and long-term complications, Graham said. Beyond the cost per pill, one must consider medical visits, laboratory monitoring, associated adverse events and hospitalizations, “not to mention indirect costs like quality-of-life measures,” she said. “You need to add all of that up and offset it with the number of people cured.”
“There is an argument that if you spend $84,000 now, you might save downstream costs. The problem is that nobody has proven that yet,” Hill told HCV Next. He added that it is also too soon to determine whether patients will develop reinfection at a later time point. “We might spend half a million dollars and achieve nothing.”
“Some patients go through their whole lives with HCV and have very few treatments of complications. Very few patients undergo transplantation, so that overall cost on the system may be negligible, relative to the cost of treating hundreds of patients with high-cost drugs who would never need a transplant,” Hill said. “These drugs might be cost-effective on a cost-per-cure level for a few people with the most serious disease, but to say it is cost-effective for everybody is incorrect.”
Moreover, according to Hill, the sheer cost of treating so many patients may put a great deal of stress on health care systems around the world.
Gilead Sciences offered another opinion on the matter. “Government systems like the VA, prisons, Medicare and Medicaid will bear the long-term medical costs of liver cancer, liver failure and transplant, and therefore are the systems that will benefit most from the availability of new therapies for HCV,” a Gilead spokesperson said. “Gilead works with these systems to address both the short-term impact of up-front drug costs, but also the long-term impact of untreated HCV (or poorly managed HCV) on their budgets.”
Tracy Swan, hepatitis/HIV project 𠊍irector at the Treatment Action Group, said downstream complications may indeed be reduced by more effective therapies, but the current generation of drugs is not completely free of associated costs. “In the United States, as it becomes simpler to treat people with mild to moderate liver disease, the pool of qualified non-specialist providers is likely to expand, and that is when insurers are likely to balk at paying for expensive treatment, and limit access,” she said in an interview. “Patients and their clinicians may have many hoops to jump through.”
According to Dusheiko, the health care system in the United Kingdom will face similar challenges. “We will be at the mercy of budget allocations. Cost-effectiveness, in terms of preventing downstream morbidity, does not equate with affordability,” he said.
Fried encouraged the clinical community to look at the bigger picture. He cited findings from van der Meer and colleagues, whose data indicated that 𠊊ll-cause mortality diminished just by treating HCV infection, albeit with an interferon-based regimen. “It is difficult to parse out all causal reasons,” he said. “But it is possible that other disease states and comorbid conditions will benefit from effective, tolerable therapies.”
Who to Treat
With such macroeconomic factors in play, the health care community may be required to prioritize treatment groups. 𠊊rguments have been made to treat children first, or individuals coinfected with HIV, injection drug users, prison inmates, patients in mental health facilities or, simply, patients with the most severe disease. But this may place the health care community in a situation where the ethical and moral obligation to treat patients comes into conflict with price and limited resources, according to Raymond F. Schinazi, PhD, DSc, the Frances Winship Walters professor of pediatrics at Emory University School of Medicine.
Raymond F.
Schinazi
“If we treat only the sickest people who are going to die first, it will equate to just about 5% of the epidemic,” Hill said. “In that case, the epidemic just carries on into the future 𠊏or another 10 years, 20 years or more.”
With such effective drugs, eradication is a real possibility, at least theoretically, Hill said. “We would like to treat everybody and reduce transmission. But at current prices, that is simply impossible.”
Members of the House of Representatives Committee on Energy and Commerce — including ranking members Henry Waxman, D-Calif., Frank Pallone Jr., D-N.J., and Diana DeGette, D-Colo. — recently wrote an open letter to the CEO of Gilead Sciences addressing this very issue. “Our concern is that a treatment will not cure patients if they cannot afford it,” the letter said.
However, Schinazi said it is unlikely, at least in the United States, that insurance companies will “deny treatment with the best combination of DAAs for patients who have severe liver disease or who are coinfected with HIV. There is an acceptable price for performance, and curing these difficult-to-treat patients is an ethical and moral obligation.”
Providing Assistance
The spotlight may be on the pricing structures of the new drugs, but help is being offered.
For payment assistance, Janssen has developed the Olysio Savings Program to provide financial aid to qualifying patients by limiting co-payments to $25.
Similarly, Gilead Sciences developed the Support Path program to provide financial aid to qualifying patients who are uninsured, underinsured or need financial assistance. “Key components include the Sovaldi Co-pay Coupon Program, which minimizes monthly out-of-pocket costs for eligible patients to as little as $5 per month, and the Support Path Patient Assistance Program, which will provide Sovaldi at no charge for eligible patients with no other insurance options. Gilead also has provided support to an independent nonprofit organization that provides assistance for eligible federally-insured and privately-insured patients who need help covering out-of-pocket medication costs,” a Gilead spokesperson said.
“The companies are making a commitment to help people who might not be able to access the drug up to a pretty high level,” Clary said.
Countries with a high prevalence of HCV such as India, Pakistan and China may also receive financial support and lower costs. For example, Gilead Sciences announced plans to license sofosbuvir to a number of Indian generic pharmaceutical manufacturers. Final details of the program in India are expected in coming months. In March, the company announced that it will offer sofosbuvir to Egypt at a 99% discount to the US price.
Driving Down Costs
Some experts said they believe that the cost of the drugs will come down, but how and when that will happen remains in question. Graham said it may be within the year that the clinical community gets some indication as to how the competition may shake out.
“Competition may drive the price down later, but not just yet,” Dusheiko said.
Hill said, “At some point, there will be a showdown.”
Looking further afield, the duration of treatment continues to decrease, according to Schinazi. “We might get down to a 6-week course, or a 4-week course, which will be cheaper,” he said. “Then maybe we will have cheaper injectable nanoparticle formulations that can be delivered once a month. Patients may not even have to take a pill anymore. We are seeing this in HIV. But, we are not there yet with HCV.”
Fried offered a broader perspective. “Has there ever been a drug that hit the market where cost wasn’t a discussion?” he asked. “The field is changing rapidly. We may be having a different conversation 6 months or a year from now, and we should realize that the evolution of treatment of this disease has been unbelievable. It is a life-changing event.”
With this in mind, Clary said he hopes that the next wave of HCV drugs would also be priced reasonably and is trying to focus on the positive. Despite the price tag, Clary sees hope in the current state of HCV treatment. “The recently approved drugs and all of the therapies in pipeline mean a cure — a potential revolution for an overwhelming number of people.” — by Rob Volansky
References:
Hagan LN. J Viral Hep. 2013;20:847-857.
Hill A. Clin Infect Dis. 2014;doi:10.1093/cid/ciu012.
Iskowitz M. Olysio simeprevir cost? Hepatitis C New Drug Research and Liver Health. Nov. 26, 2013. Available at: hepatitiscnewdrugresearch.com/-olysiotrade-simeprevir-cost.html.
Perrone M. Medical groups question price of new hep C drug. Associated Press. March 11, 2014. Available at: bigstory.ap.org/article/medical-groups-question-price-new-hep-c-drug.
Reau NS. Hepatology. 2014;59:1246-1249.
Sethi N. Abstract #1847. Presented at: The Liver Meeting 2013; Nov. 1-5, 2013; Washington, D.C.
US House of Representatives Committee on Energy and Congress. Open letter to Dr. John C. Martin. March 20, 2014. Available at: democrats.energycommerce.house.gov/sites/default/files/documents/Martin-Gilead-Sciences-Hepatitis-C-Drug-Sovaldi-Pricing-2014-3-20.pdf
van der Meer AJ. JAMA. 2012;308:2584-2593.
For more information:
Geoffrey M. Dusheiko, MD, can be reached at UCL Institute for Liver and Digestive Health, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, United Kingdom; email: g.dusheiko@ucl.ac.uk.
Michael W. Fried, MD, can be reached at UNC Liver Center, Burnett-Womack Building, UNC at Chapel Hill, Chapel Hill, NC 27599; email: mfried@med.unc.edu.
Camilla S. Graham, MD, MPH, can be reached at BIDMC Division of Infectious Disease, 110 Francis St., Suite GB, Boston, MA 02215; email: cgraham@bidmc.harvard.edu.
Andrew M. Hill, PhD, can be reached at Liverpool University Department of Pharmacology and Therapeutics, 70 Pembroke Place, Liverpool L69 3GF, United Kingdom; email: microhaart@aol.com.
Raymond F. Schinazi, PhD, DSc, can be reached at Emory University School of Medicine/VA Medical Center, 1760 Haygood Drive, Room E-418, Atlanta, GA 30322; email: rschina@emory.edu.
Tracy Swan can be reached at tracyswan@verizon.net.
Disclosures: Clary, Graham, Hill and Schinazi report no relevant financial disclosures. Dusheiko reports associations with Gilead and Janssen. Fried reports associations with AbbVie, Bristol-Myers Squibb, Genentech/Roche, Gilead, Merck, Novartis, Tibotec/Janssen and Vertex. Reau reports consulting for and receiving grants from AbbVie and Gilead; consulting for Idenix; and grants from Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Janssen and Vertex. Swan reports associations with the Hepatitis C Community Advisory Board.