The Cost Burden of a Cure: Treating HCV

With the recent availability of the interferon-free combinations of direct-acting antivirals (DAAs) for hepatitis C viral infection (HCV), patients now have a highly effective treatment without the dismal side effects that interferon-based therapies offered in years past.

Since the Food and Drug Administration (FDA) began approving this new class of oral agents for HCV in 2014, outcomes data show that these drugs are associated with high cure rates (exceeding 90%) with reduced toxicity. 

But as is all too true in the world of healthcare delivery, and increasingly in specialty pharmacy, availability does not translate into accessibility or feasibility given the high cost of these drugs that prohibits their affordability to individual patients and their feasibility as a viable public health treatment option. While more recently approved drugs have dropped in price, a 2015 Institute for Clinical and Economic Review (ICER) report listed the price of these drugs between $65,000 to $190,000 for an 8- to 24-week treatment course.

“The major issue about the Hepatitis C drugs is the combination of price and prevalence,” Kevin A Schulman, a professor of Medicine atDuke University, said in an interview. “We’ve not faced prices like this for a drug that potentially impacts 3% to 4% of the populations.”

Highlighted in Dr Schulman’s concise and precise diagnosis of the challenge of incorporating the new costly HCV agents into widespread clinical practice is the current debate on the most cost-effective way to manage HCV given its prevalence.

It is estimated that 2.7 million Americans are infected with HCV, with higher estimates up to 5.2 million when including specific populations such as people in prison, nursing homes, hospitals, military service, and the homeless.

If left untreated, 20% to 30% will develop liver cirrhosis after 20 years and of these about 4% of patients a year will develop hepatocellular carcinoma (HCC). The cost of treating these liver complications once the disease has advanced this far poses a burden to public health.

Another public health burden, however, comes at the opposite end. If all patients who are screened for and diagnosed with HCV are immediately started on treatment, the cost is prohibitive, both at the individual and societal level.

Writing in a recent commentary, Fox and McCombs posed the challenge to payers as such: “When is it appropriate to delay a potentially lifesaving treatment? Should treatment decisions be based purely on economic grounds?”

“In the United States, these questions confront payers and government programs covering patients with hepatitis C virus (HCV) infections,” they wrote. The main driver of this debate is the high cost of the new HCV agents.

Cost-Effectiveness of New HCV Agents

One way to study the high cost of these drugs is via a cost-effectiveness analysis. Such a study was recently published by Chahal and colleagues looked at the cost-effectiveness of treating all patients with HCV versus only those with advanced fibrosis. They also assessed the cost-effectiveness of treating patients at each stage of fibrosis. They based their cost-effectiveness analysis on the price and effectiveness of the drug Harvoni (ledipasvir-sofosbuvir; Gilead).

Using a decision-analysis model for the treatment of HCV genotype 1, the study found that decreasing the cost of the new HCV drugs by about 46% reduces the incremental cost-effectiveness ratio by nearly one-half. The lower the cost of the drug, explained lead author of the study, Harinder Chahal, PharmD, MSc, the more cost-effective it is to treat a patient without or with minimal liver damage (ie, patients with earlier fibrosis stages).

Dr Chahal, of the Department of Clinical Pharmacy at University of California, San Francisco, illustrated the meaning of this by citing the following example.

“At retail prices, treating just 50% of genotype 1 patients over the next five years will cost $53 billion,” he said. “However, with a 46% reduction in drug costs, that figure is reduced to $29 billion.”

This would also affect the burden of HCV costs on the overall health system. “A further reduction in drug costs will result in a decreased price tag for health systems, allowing treatment and cure for more patients living with hepatitis C,” he said.

Although the study did not look at the cost of HCV for individual payers, Dr Chahal cited the 2015 ICER report that he coauthored on the cost-effectiveness of interferon-free therapy for chronic HCV.

“The general finding of budget impact analyses of various payers was that a ‘price range of $34,000-$42,000 for new regimens would be required to allow treatment of all individuals with known infections while keeping per-member-per-month (PMPM) cost increases to 0.5%-1%,” he said. “Which is the maximum increase many insurers consider manageable without special measures.”

Potential Solutions

One solution that may already be occurring is the decrease in price due to increased competition. Dr Chahal noted that since their cost-effectiveness study was published in 2015, newer HCV drugs have been approved with substantially reduced price tags and shorter duration of treatment for some patients. For example, Mavyret (glecaprevir/pibrentasvir; Abbvie), approved in August 2017, carries a price tag of $26,400 for an 8-week course and $39,600 for 12-week course. Compared to Harvoni, which carries a price tag of $63,000 for an 8-week course and $94,500 for a 12-week course, this price difference is substantial.

“The cost of new treatments is decreasing with increasing competition,” said Dr Chahal. However, he emphasized that the budget impact may remain too high for some payers to treat millions of HCV patients.

“Further cost reductions of once-daily oral, pan-genotypic drugs are needed and should be actively pursued through discount negotiations,” he said, emphasizing that the high costs of the current drugs and the number of patients requiring treatment continue to limit who can get HCV therapy and at what stage of liver damage – “even with the confidential discounts given to different payers by the manufacturers.”

Another solution proposed is triaging patients based on disease severity. The Fox and McCombs report suggested a treatment strategy that prioritizes treatment of patients with any evidence of significant disease progression and to treat all of these patients over a 3 to 5 year period. Priority should be given to patients who are the most severely ill. They propose an index based on common blood tests (FIB4) that can be used to monitor disease progression, and propose using FIB4+ as the critical value at which to begin therapy. After all patients with significant disease progression are treated, they then propose screening all existing and newly diagnosed patients with HCV and begin treatment in patients when they exceed the FIB4 value.

“Treat everyone who needs treatment, as soon as they need treatment, but not before they need it,” they concluded

Another strategy being used by payers is to treat patients once they progress to liver fibrosis (e.g., fibrosis stage 2 or 3). James G Kahn, MD,  of the Institute for Health Policy Studies and Global Health Economics Consortium at the University of California, San Francisco, a coauthor of the cost-effectiveness study with Dr Chahal, agreed with this approach.

“If done carefully, this approach allows focusing limited resources on those individuals who most need treatment, with little clinical downside,” he said.

However, he emphasized that it is essential to track how individuals are doing, and to treat early.

“Even with the 2015 costs, we found a substantial portion of treatment costs offset by averted healthcare costs,” he said. “With lower drug prices, more and earlier treatment makes sense.”

Finally, Dr Schulman, who just published an editorial on the challenges posed by high drug costs, suggests that perhaps “draconian restrictions” to access of high cost drugs is “the only way medicine can send a strong signal to innovators that their future rewards are tied not just to scientific advancement but also to affordability.”

“Clinicians originally implemented a concept of avoiding therapy for clinical toxicity while they waited for more efficacious and less toxic therapies,” he said. “I don’t think it’s an issue at all if we adopt the same approach to financial toxicities in therapy. It’s a shame that the price of these therapies leads to this consideration, but setting the price was a deliberate decision on the part of the manufacturer.”