Who has the power to prescribe medications? In the ongoing struggle to cure the estimated 3.2 million people living with chronic hepatitis C virus (HCV) infection in the U.S., the answer may not be who you think. While common sense may suggest that you and your doctor have the final say over what medications you take, HCV treatment advocates warn that a net of restrictions, gatekeepers and business deals are increasingly tying doctors' hands as far as what they can do for their patients who need HCV treatment.
The knots binding prescribers' hands got tighter and more complex as the companies that make the newest (and most expensive) generation of HCV drugs cut exclusive deals with pharmacy benefits managers (PBMs). In the U.S., a PBM is usually a third-party agency that processes and pays out an insurance company's prescription drug claims. It also handles creating formularies, which are the lists of approved drugs available to people with particular health insurance plans.
The current controversy began in December 2014, when Express Scripts, the nation's largest PBM (with access to 25 million patients), agreed to an exclusive deal with AbbVie, maker of the recently approved HCV regimen Viekira Pak (ombitasvir, paritaprevir and ritonavir tablets co-packaged with dasabuvir tablets). The deal made Viekira Pak the sole treatment option for those living with HCV who have Express Scripts as their PBM. Steve Miller, M.D., chief medical officer of Express Scripts, told The New York Times that the deal would yield "a significant discount" over Viekira Pak's sticker price of $83,319 for a standard 12-week treatment course.
Then, in January, a number of PBMs -- including CVS Health, Anthem and EnvisionRx -- reached similar deals with Gilead Sciences for exclusive distribution of its HCV drugs, Harvoni (ledipasvir/sofosbuvir) and Sovaldi (sofosbuvir). Gilead drew the ire of many advocates last year after setting a high retail price for Sovaldi, the first of a new wave of HCV drugs that offer higher cure rates, fewer side effects and a faster course of treatment than older alternatives. Sovaldi's price was set at $84,000 for a 12-week regimen, or $1,000 per daily pill. Harvoni comes in at about $94,500 for a 12-week regimen, or about $1,125 per daily pill. Gilead's exclusive PBM deals suggest lower drug prices for people who are covered by those PBMs, although specific numbers have not been released.
While deals like these are actually common, the arrangements reached by Gilead and AbbVie for their HCV drugs are more restrictive than usual. A deal between a pharmaceutical company and a PBM makes that company's drug the preferred option for people whose insurance plans are handled by the PBM. However, these deals may put access to any HCV drug that is not the preferred regimen out of reach -- and these new drugs are not all equally effective or useful for every person living with HCV.
"This Weird Rube Goldberg Machine"
Though most popularly known for its work in fighting the HIV/AIDS epidemic, the AIDS Coalition to Unleash Power New York (ACT UP NY) recently turned its attention to HCV, according to member Annette Gaudino. For Gaudino, these drug access wars are bad news for patients. "The drug that your doctor prescribes should reflect your hepatitis C genotype and the success that the drug's going to have in treating your version of the virus, not the exclusive deal that the PBM that you happen to have has," she said.
In layperson's terms, according to Gaudino, "Competition equals good, exclusivity equals bad. Our demand remains that treatment decisions be guided by the clinical judgment of treating physicians, not cost." Gaudino warned that the growing number of exclusivity deals is adding more complexity to an already complex system that creates "this weird Rube Goldberg machine in which, in the end, what winds up happening is everybody in this clusterf*** daisy chain gets paid -- and we all get screwed."
Proponents of the PBM deals say that they will ultimately drive down the cost of treatment. Gaudino is quick to deny that claim. "The only way that you can argue that exclusivity deals drive costs down is that in pitting two very similar drugs against each other, it incentivizes somewhat of a price war between the two manufacturers and those two drugs," she said. However, "These exclusivity deals are just [about] who gives the biggest discount. CVS got their exclusivity deal and Express Scripts has theirs. And they're happy. I don't really see the pharmaceutical companies coming back with bigger discounts. Because why should they, right?"
With PBMs hoping for a discount rather than an ongoing battle that drives down prices further over time, patients may still be left paying far more for an HCV cure than they should, Gaudino suggests. Advocates also note that while the PBM deals may offer a slight discount, the list prices of the drugs remain exorbitant. As Tracy Swan, hepatitis and HIV project director at Treatment Action Group (TAG), noted in an earlier interview, "We keep hearing, 'This is cheaper than this that and the other,' but that's like saying, 'It's cheaper to buy a Cadillac now than it will be to buy a Cadillac in five years,' and it has nothing to do with what it actually costs to produce the Cadillac."
In that earlier interview, Swan expressed similar concerns to Gaudino's over the scope and power that PBMs exert in deciding patient treatment regimens. "Although anything that increases access to treatment is a great thing, I really am not comfortable with the idea that your insurance company, rather than yourself with your own physician, decides what treatment is right for you," she said. "I think we're walking down a dangerous road when we start going that way."
"Ultimately, it seems like doctors are really losing their purview to prescribe," Swan added. "That's what you're supposed to do when you're a doctor. You're not supposed to say 'Let's see what your insurance company will pay for.'"
Discounts for Insurers, Not Necessarily Patients
So far, little evidence has emerged that those accessing the new generation of HCV cure drugs will feel any monetary relief as a result of the PBM deals. According to The New York Times, the discounts may help with the health care costs for employers, but those living with HCV "will probably not notice an immediate cost difference, such as lower co-payments."
According to InvestorPlace, Gilead's stock took a 20% dip in less than a week after competitor AbbVie announced its exclusive PBM deal with Express Scripts, which the business website called potentially "alarming to investors." To Gilead, the deal meant that its drugs, Harvoni and Sovaldi, would "miss out on a portion of the 3 million patients in the U.S. and 150 million afflicted globally." After Gilead's deal, shares in its company rebounded, "driving up the entire biotech sector," according to CNBC.
Ultimately, though each PBM's move may end up giving its beneficiaries greater access to HCV cure drugs and will satisfy each pharmaceutical company's monetary interests, advocates warn that it may come at a great price: the quality of care a patient with HCV can expect, and the ability for doctors to give a patient what is best for them.
A "Terrible" Environment for Prescribing
When a doctor wants to prescribe a medication to a patient that may deviate from the patient's insurance's formulary, the process includes an amount of paperwork so daunting that it may ultimately overwhelm the doctor, clinicians warn.
"The environment for prescribing, now that we finally have truly effective and almost completely safe medications, has become terrible," said Daniel Fierer, M.D., a leading HCV physician-researcher and associate professor of medicine at the Icahn School of Medicine at Mount Sinai Hospital. "It's become incredibly onerous to prescribe, including being unable to prescribe for many patients due to not clinically-indicated but presumably cost-driven attempts to save money by denying treatment to people who are not the sickest."
According to ACT UP NY's Annette Gaudino, the genesis of the restrictive nature of HCV cure access goes back to guidelines set forth by the American Association for the Study of Liver Diseases (AASLD). The guidelines were meant to prioritize treatment for the sickest people: those with Stage 3 and Stage 4 liver disease and coinfections. However, with the exorbitant pricing of the newer HCV drugs set to bankrupt state Medicaid programs, many insurance companies limited access to these drugs to people who had Stage 3 and Stage 4 liver disease, Gaudino said.
Fierer cited a specific case that backed up Gaudino's assertion. "It's only Medicare, actually, that ends up covering it, sometimes with a single application," he said. "But others, after a month of letter writing, got completely denied, saying an HIV-infected person with Stage 2 fibrosis is not sick enough."
One time, after a fourth appeal for a patient in need of treatment, Fierer tried peer-to-peer contact with the insurance company. "The peer just said, 'Send in your written report.' There was absolutely no discussion. She said, 'I'm just here to tell you that the answer is no; but you can send in a letter.'"
"It was astonishing to me that you can say an HIV-infected person with Stage 2 fibrosis is not good enough," Fierer said.
Meanwhile, the repeated attempts to secure coverage for their patients' HCV treatment have taken up an increasingly large amount of time and energy, Fierer added. "The only people who are not personally overwhelmed as physicians are ones who have a crew of navigators and people who can do it. It's overwhelmed my office practice and both of my [Mount] Sinai practices and, anecdotally, others around me: the paperwork, the automatic denials, the requirements from every different decision maker, having different criteria, almost non-consistent with any possible clinical care."
If doctors get into their careers to help heal the sick, then the ability to do that job is the hardest it's ever been, according to Fierer. "It is frustrating for me. It's much more work than it ever has been," he said. "They have successfully, for the first time ever, put up enough barriers."
Are Any Drugs Better Than No Drugs?
With lines of bureaucratic red tape appearing to increase between people with HCV and the drugs that could cure them, TAG's Tracy Swan thinks this might be creating a mentality that any treatment is better than no treatment.
"With all the news coverage about how expensive the drugs are and how no one is getting them, I think it's sort of grinding people down to make them feel that they're lucky to get anything, instead of really thinking with their medical provider, 'What's the best treatment for me?'" she said.
In addition, HCV affects some of society's most marginalized populations, who may have more of a need to fine-tune treatment. According to the CDC and the New York City Department of Health and Mental Hygiene, HCV is most frequently associated with injection drug users and baby boomers, and is also highly prevalent in black communities. Occurrences of HCV are also especially high in areas of poverty and with a lack of access to quality education.
The Racial and Ethnic Approaches to Community Health across the US Risk Factor Survey (REACH US RFS) showed that blacks, Latinos, Asians and American Indians had the highest HCV infection rates (9.2%, 8.3%, 6.8% and 6.4%, respectively). The study also found that a large percentage of those surveyed were not tested for HCV, meaning that actual HCV prevalence in these communities is likely to be much higher than what is reported.
"We're talking about a lot of ex-prisoners, current prisoners, very poor people," said Gaudino.
Coinfections and contraindications -- drug-to-drug interactions or other medical considerations in a person's life that mean he or she cannot be prescribed a certain drug -- are more likely to be present among these people, experts say. And that means that restrictions on which drug can be used may have a bigger impact on whether someone is able to be treated or cured.
Other people who might be ill-served by prescription barriers are women on birth control or who are pregnant. According to Viekira Pak's prescribing guide, the drug regimen cannot be used with ethinyl estradiol-containing products, which are among the most common forms of birth control. In addition, most people who are prescribed Viekira Pak will need to take it with another drug called ribavirin -- but ribavirin is known to have the potential to cause fetal death or fetal abnormalities.
About 25% of people living with HIV in the U.S. are also living with HCV. Viekira Pak is contraindicated with many popular HIV medications, including rilpivirine (Edurant), lopinavir/ritonavir (Kaletra), ritonavir (Norvir), darunavir (Prezista), atazanavir (Reyataz) and efavirenz (Sustiva, Stocrin). Harvoni also has a restrictive list of contraindicative HIV medications, including lopinavir/ritonavir and tenofovir (Viread) (part of Atripla and Truvada). For people living with HIV/HCV coinfection, having to navigate an insurance bureaucracy may not be helpful to their health -- especially if they're only being considered for treatment because of their advanced liver disease.
Both Fierer and Swan expressed reservations about how well populations prescribed Viekira Pak would be able to tolerate ribavirin, as well. Most side effects from early HCV treatment regimens -- ribavirin along with interferon -- were assumed to be due to the interferon. But Fierer said that personal experience has changed his opinion. "In the year that I've been prescribing sofosbuvir, I found that a lot of people had a lot of pretty bad side effects from the ribavirin -- more than is typically reported -- and now I'm rethinking how a proportion of the side effects came from ribavirin."
Those assigned Viekira Pak may be challenged by the extra pill burden, as well. "[Viekira Pak's] got a few more moving parts -- the twice a day; the ribavirin in it. It may end up having a little bit worse efficacy than in clinical trials, compared to the decrement that we'll see from Harvoni," Fierer added.
Compounded with price and drug interactions, alcohol and drug use may be a limiting factor for those wishing to access treatment. Often, liver disease is a consequence of alcohol and drug abuse, meaning that those with damaged livers who may be prime for HCV treatment may be the first to be refused.
For Gaudino of ACT UP NY, this sends a devastating signal to populations that may already struggle with issues of self worth. "You're going to tell me that you have a drug that will save my life. But you're not going to give it to me until I become sober," said Gaudino. She added, "What would you do? I would drink. I would go use drugs."
Telling a Patient No
HCV infection is a deadly disease, and it often affects those who are not in the best health to begin with. Yet the picture that advocates and clinicians paint is one in which people with liver disease must wait to be treated while piles of forms and still-steep drug prices continue to block access to a cure that, paradoxically, should be easier to achieve than ever thanks to the newest generation of drugs.
Somewhere, below the mounds of paperwork, beyond the PBM deals and behind insurance company drug formularies, these questions lie: What is the value of a human life? How can we best cure what ails us?
Gaudino believes the answer is unequivocal: "Treat to the label. Unless there is a medical contraindication, everyone who has hepatitis C who wants access to these drugs should get access to these drugs, regardless of where they are in their disease. Because it is a cure. And no one should have to wait to get sick to get cured."