When Gilead’s Sovaldi (sofosbuvir) was approved in December 2013, it was viewed as the beginning of a new era in hepatitis C treatment and the end of an old paradigm. Suddenly, a disease that was difficult to treat and could rage on for years could be cured within 12 weeks. Ten months after getting Sovaldi approved, Gilead received another approval for its two-in-one hepatitis C medication, Harvoni (ledipasvir/sofosbuvir), which was quickly followed by the approval of AbbVie’s Viekira Pak (ombitasvir/paritaprevir/ritonavir) in December 2014.
It all happened in one year—the introduction of three separate treatments for hepatitis C, news of several more in development from Merck and Johnson & Johnson, and the introduction of a new class of specialty drugs that cost between $83,000 and $94,500 for a complete treatment regimen. It was historical. Within a year, Gilead’s hepatitis C drugs, which grossed $12.4 billion in the first year, became the top-selling new products in the history of the pharmaceutical industry.
Never has a class of drugs been so frequently discussed and analyzed from every perspective. Of course, there has been a lot of efficacy analysis for these meds broken down population by population. And there have been reams of pharmacoeconomic data aimed at payers, who have had to make hard decisions—decisions about which drugs to use, in which patients, at what point in their illness.
However, there is one factor which until very recently has been either ignored or heavily discounted: The issue of safety and its impact on cost.
A week before the FDA issued a warning about Viekira Pak and made AbbVie update its label to reflect increased risk of liver injury, hepatic decompensation and liver failure in patients with cirrhosis (which is 15% to 30% of all hepatitis C patients), Advera Health Analytics, a health informatics company based in Santa Rosa, CA, had picked up the safety signal as part of their ongoing analytics. Using data from the FDA’s Adverse Event Reporting System (FAERS), Advera prepared a Drug Safety Monitor Report on Harvoni and Viekira Pak, highlighting the safety risks of Viekira Pak and quantifying the costs associated with those safety problems.
"Increasingly, safety is being factored into the overall value equation," said Brian Overstreet, President of Advera Health Analytics, in an interview with BioPharma Dive. "Payers, as well as hospital systems, are starting to take risk mitigation, downstream medical costs, patient safety and the rate of adverse events into account during the decision-making process."
How safety factors can increase overall costs
Using adverse event reports obtained from the FDA after a Freedom of Information Act (FOIA) request was filed, Advera estimated the increased cost per prescription of each of the hepatitis C treatments when all of the downstream safety consequences—hospitalization, additional medical care, etc.—were factored in.
Here’s what they found: Based on the most up-to-date adverse-event reporting, the cost per prescription for Viekira Pak increased by 200% to $151 (taking into consideration the entire population of patients), while its RxScore (scored 0 to 100, with higher scores indicating more risk) increased by eight points to 73.93. In contrast, Harvoni had a 32% drop in cost-per-prescription to $60.24 and an RxScore of 68.98. In the final analysis, Harvoni proved to be much safer than Viekira Pak.
The implications of these numbers cannot be discounted. And although Express Scripts (which chose Viekira Pak over Gilead’s drugs based on a better deal) has not chosen to change its formulary, there are P&T committees nationwide meeting to discuss newfound safety concerns around Viekira Pak.
But why wasn’t this issue considered before? Overstreet refers to safety as “the red-headed stepchild,” which is seen as nebulous and open-ended in terms of its role in valuation. But that’s changing.
“With drugs like hep C drugs that are curative, you can take effectiveness and efficacy off the table and focus on safety. Right now, payers are starting to focus on how improving safety can reduce costs, and hepatitis C is a testing ground,” he said.
When efficacy is no longer a concern, safety is key
The fact that safety is becoming an issue worth paying attention to for payers and other stakeholders is actually a good thing. It’s a byproduct of innovation and success in the industry. “There are always going to be classes of drugs where efficacy is most important. For example, in oncology, where you are measuring success in additional months of life or improved quality of life, efficacy is number one and there is more willingness to deal with risks,” Overstreet explained.
“However, because of the success of some of the new specialty drugs, including curative hepatitis C regimens and other genomically-based drugs, safety will now be an important part of the conversation. Payers need to understand what the cost is going to be outside the medication costs and need to look at how safety-related costs can impact the bottom line over at least a five-year period.”
While post-marketing studies and real-world studies were once conducted only in special cases, post-marketing surveillance is now the norm. And the data from these studies, along with FAERS, help tell an important story about how much drugs really cost when efficacy and safety are taken into consideration.