As you probably know, Sovaldi (sofosbuvir) is an important new treatment for Hepatitis C infection that was released this last December and has been aggressively marketed by its maker, Gilead, ever since. The problem is that Gilead is charging an unheard of, jaw-dropping, $1,000.00 per pill for Sovaldi. This translates into a MINIMUM of $84,000.00 for Sovaldi alone for the simplest course of Hep C treatment. Add on the other necessary drugs and take into consideration more complicated cases, and a single course of therapy for Hepatitis C will cost between $100,000.00 and $250,000.00.
This price has placed prison systems in a no-win situation–and not just prisons, but also Medicaid, insurance companies, and HMOs. On one hand, Sovaldi is a good drug that, in fact, represents a significant advance in Hepatitis C treatment. Lots of Hepatitis C patients could potentially benefit from Sovaldi. On the other hand, no one can afford Sovaldi. Treating every potential Hep C patient using Sovaldi would bankrupt everyone. There is no good way out of this dilemma.
Brief Historical Overview
Hepatitis C, of course, is an RNA virus transmitted almost exclusively via blood exposure. Most of the people who are infected with Hepatitis C today contracted the disease prior to 1992 from a blood transfusion. That is why the CDC issued a call for all “Baby Boomers” to be screened for Hep C, since the majority of unrecognized Hepatitis C cases are Baby Boomers. Since the blood supply was cleaned up in the early 90s, the rate of new cases of Hepatitis C have dropped dramatically. Almost all of the new cases are due to IV drug use and sharing needles. Hep C can also be transmitted inside a prison via prison tattoo needles.
Out of every 100 patients who are infected with Hepatitis C, 75-85 will become chronically infected and 60-70 will develop chronic liver disease. Most of these chronically infected patients will remain asymptomatic. 5-20 will eventually develop cirrhosis (usually after 20-30 years) and 1-5 will die from Hepatitis C, either from liver failure or cancer. The goal of treating Hepatitis C patients is to stop progression of liver damage in those who have it.
The first anti-viral drug used to treat Hepatitis C was interferon but only about 15% of the patients treated with interferon were able to totally clear the virus from their systems—which is called a “sustained virologic response (SVR).” Not very good. It was then found that attaching a Polyethylene Glycol (PEG) molecule to interferon markedly increased interferon’s effectiveness (by interfering with the body’s ability to eliminate the interferon). This is called “Pegylated interferon,” and PEG interferon increased virus elimination to the range of 30% of those treated.
The next advance in Hep C treatment was the development of the oral nucleoside analogue ribavirin. Adding ribavirin to PEG-interferon increased the overall effectiveness of the treatment among all comers to around 50%.
Finally, in 2011, the protease inhibitors telaprevir and boceprevir were released. When one of these agents was added to PEG-interferon and ribavirin (the so-called “three-drug regimen”), even better SVR rates could be obtained in an even shorter amount of time, especially for Genotype One, the most common and hardest to treat sub-type of Hepatitis C. The three-drug regimen improved SVR rates in Genotype One from around 40% to around 55% of those treated. SVR rates in Genotypes two and three are closer to 85-90%.
However, there are significant problems with this triple therapy. First, it is hard for many patients to tolerate, the worst drug in this regard being PEG interferon. Many patients with Hepatitis C just cannot tolerate the vicious side effects of PEG-interferon. Second, it involves a lot of pills and shots, which is termed “the pill burden.” And of course, the more pills you have to remember to take, the more likely you are to forget doses or otherwise be non-compliant. Third, treatment lasts a long time—48 weeks. It is very hard for patients to tolerate the nasty side effects and remember to take all of the pills at the right time for that long. And finally, triple therapy is really expensive. I remember at one conference on Hepatitis C that I attended where this comparison was made: “For every offender treated for Hepatitis C (with triple therapy), that is one correctional officer that you cannot hire that year.”
The potential game changer is Sovaldi (sofosbuvir), which represents a new class of agents termed “polymerase inhibitors.” Sovaldi has a whole bunch of advantages over the old triple therapy.
1. Treatment times using Sovaldi are shorter—in fact, a lot shorter. The basic treatment course for genotype one is only 12 weeks long compared to 48 weeks.
2. Sovaldi regimens seem to result in higher SVR “cure” rates. For Genotype One, Sovaldi may boost the SVR to over 85%.
3. Sovaldi is dosed once a day, markedly cutting down the “pill burden” for Hepatitis C, which should increase compliance.
4. Sovaldi regimens have fewer drug interactions and fewer side effects. In fact, those patients with Genotype One who cannot tolerate PEG interferon can instead combine Sovaldi and ribavirin and another new Hep C drug, the protease inhibitor Olysio (simeprevir). This means that many patients, who were ineligible for Hepatitis C treatment before Sovaldi, could now be treated. Examples include patients with concomitant diseases like HIV, advanced liver disease and hepatocellular cancer. This also means that all of the thousands of Hepatitis C patients who failed PEG interferon therapy due to side effects can now be re-treated interferon-free. I suspect most of them will want this.
5. Finally, the Infectious Disease Society of America (IDSA) and the American Association for the Study of Liver Disease (AASLD) this last January jointly issued new guidelines for the treatment of Hepatitis C that recommend Sovaldi as a first line therapy for all genotypes. They do not recommend using the protease inhibitors telaprevir and boceprevir at all.
The result of all of this is a potential huge demand for Sovaldi. Liver specialists want to treat the thousands of patients who are ineligible for interferon. Patients who have failed interferon therapy want another shot at a cure. Some liver specialists are even advocating for the treatment of all patients with Hepatitis C, even if they are asymptomatic. Advocacy groups are getting into the act and demanding free access to Sovaldi. The CDC recommends that everyone in the United States born between 1945 and 1965 (Baby Boomers) be tested for Hepatitis C infection. Those thousands found to be positive are going to want to be treated. Gilead is advertising heavily and, to judge by a Gilead rep at a conference I recently attended, is using the IDSA/AASLD guidelines to say that Sovaldi is the “standard of care.”
At What Cost?
The problem is the cost. Gilead has chosen to price Sovaldi at $1,000.00 a pill, or $84,000.00 for a 12 week course of therapy. With interferon and ribavirin, the total cost to treat Genotype one is over $110,000.00. Genotype 3 requires 24 weeks of therapy, so double the price. If you go PEG interferon free, add another $80,000.00 for Olysio. And we thought triple therapy was expensive! It is a pittance compared to the cost of Sovaldi.
Let’s do a little hypothetical number crunching for my home state of Idaho. As of a year ago, Idaho had just short of 8,000 offenders in the DOC. Let’s assume that 20% of them are infected with Hepatitis C (a conservative estimate—it might be 30% or more). If we treat all of them with Sovaldi regimens, and, taking into account the various genotypes, treatment could average $130,000.00 per patient. Do the math: 1,600 times $130,000.00 = $208,000,000.00. This number dwarfs the entire Idaho DOC budget! It is simply financially not doable.
But won’t we save money in the long run by reducing the incidence of liver failure and liver transplant? Well, the Institute for Clinical and Economic Review analyzed this question in a paper entitled “The Comparative Clinical Effectiveness and Value of Simeprevir and Sofosbuvir in the Treatment of Chronic Hepatitis C Infection” (not yet published, but accessible here) and concluded that it would cost the state of California around $32 billion to treat half of the state’s Hepatitis C patients. But even optimistically assuming optimal cure rates and no reinfection, only around 5% of that outlay would be recouped through lower expenditures for liver transplant and treating liver failure. They conclude that Sovaldi is of “low value” in treating most Hepatitis C patients and recommend restricting its use to a small subset of patients.
$2,000.00 for Sovaldi in India?
So why is Sovaldi so expensive? Is it that expensive to produce? Well, Gilead reportedly will sell Sovaldi in India for only $2,000 for a full course of treatment and presumably will make a profit there.
According to the AIDS Healthcare Foundation (AHF), this is possible because it costs Gilead only around $1.00 a gram to produce Sovaldi, making the U.S. retail mark-up 279,000%. A Gilead executive defended this shocking price differential thus: “Gilead’s global pricing model is based on a country’s ability to pay.” Unfortunately, he is wrong if the assumption is that US third-party payers like Medicaid, Blue Cross or prison systems can afford widespread prescriptions for Sovaldi. It just cannot happen financially. Besides, that huge of a mark up just seems wrong to me, personally. It seems to be the worst sort of price-gouging.
But even putting the emotional reaction aside, the huge price leaves those of us in corrections with few options. We simply cannot afford to use Sovaldi very much, if at all.
The most obvious strategy is not to use Sovaldi and stick with the older regimens and the older protocols. Another is to authorize Sovaldi only for the sickest of the sick—those with advanced liver disease, for example or those with co-morbid conditions that preclude use of PEG interferon. A variation of this strategy is the one recommended by the Institute for Clinical and Economic Review and has been adopted by many third party payers. State Medicaid programs, like prisons, are still struggling with the issue of whom to treat.
What about the argument that since the IDSA and the AASLD have issued a guideline recommending Sovaldi for almost all Hepatitis C patients, Sovaldi now is “the Standard of Care?”
Well, in my opinion, this is simply not true. “Guidelines” do not a “Standard of Care” make.
First of all, there are many other published Hepatitis C guidelines that do not recommend Sovaldi use. The Institute for Clinical and Economic Review paper itself can be viewed as one such guideline. Several others are listed within that paper itself.
Second, the IDSA/AASLD guideline does not at all address the cost of using the drugs it recommends. When we are talking about the potential of bankruptcy if we follow these guidelines, cost is a critically important consideration.
Third, in their Hepatitis C guideline, IDSA/AASLD admitted that some of the board members had a conflict of interest: “The Panel is composed of members with personal financial relationships with commercial entities and those with no such personal financial relationships with commercial entities at the time that each Panel member was confirmed.”(see page four) I don’t know about you, but when such a huge amount of money is at stake, potential conflicts of interest make me a little leery of accepting these guidelines without reservation, especially when it is not spelled out exactly who in the panel had conflicts of interest and exactly what those conflicts were.
Finally, in my opinion, “Standard of Care” is a legal term, not a medical term. It is loaded with undercurrent implications of “I’ll see you in court if you don’t prescribe this.” I think we are better off throwing out the term “Standard of Care” and evaluating Sovaldi on its medical merits, which includes its outlandish price.
In the end, Sovaldi is a good drug that we cannot afford, except maybe in a very small subset of patients.