Two different statistical models found that novel therapies for chronic HCV infection, particularly the combination of sofosbuvir and ledipasvir, are cost effective in most patients, according to separate reports published online March 17 in Annals of Internal Medicine.

However, both groups of researchers cautioned that if these expensive agents are made available to the millions of eligible patients across the country, it would have an immense impact on health care costs for both public and private payers.

The novel therapies, which typically contain sofosbuvir in combination with ledipasvir, simeprevir, or daclatasvir, substantially reduce the length of treatment, achieve much higher rates of sustained viral response (SVR), and offer interferon-free alternatives for patients who can’t tolerate or don’t respond to standard interferon-based treatments. But it is unclear whether these benefits justify their profound expense, compared with current care. Both statistical models were developed to examine this issue, but from different perspectives.

In one study, funded primarily by the National Institutes of Health, investigators constructed a model that simulated 120 possible clinical courses of HCV-infected adults based on different ages and sexes, treatment histories, HCV genotypes, fibrosis scores, and interferon tolerances. For each of these patient profiles, they ran simulations in which patients received either “the old standard of care” (peginterferon and ribavirin, either with or without boceprevir and telaprevir) or sofosbuvir plus ledipasvir.

The average per-patient cost of standard care ranged from $15,000 to $71,000, depending on the patient profile, while that of sofosbuvir-ledipasvir ranged from $66,000 to $154,000, said Jagpreet Chhatwal , Ph.D., of the University of Texas MD Anderson Cancer Center, Houston, and his associates.

Compared with standard care, treating 10,000 patients with sofosbuvir-ledipasvir was projected to prevent 600 cases of decompensated cirrhosis, 310 cases of hepatocellular carcinoma (HCC), 60 liver transplantations, and 550 liver-related deaths, which would result in substantial cost savings. Also, compared with standard care, the incremental cost-effectiveness ratio of sofosbuvir-ledipasvir was $55,400 per additional quality-of-life-year (QALY) gained, which falls well within the accepted range for therapies for other medical conditions. Thus, the new therapy proved to be cost-effective for most HCV patients (Ann. Intern. Med. 2015 March 17 [ doi:10.7326/M14-1336 ]). But there was an important caveat: Many more patients would be eligible for the novel therapies than for the standard care, because the novel therapies are much more easily tolerated. With the addition of so many eligible patients, the resources needed to treat them “could be immense and unsustainable.” Compared with standard care, giving these novel HCV therapies to all eligible patients “would cost an additional $65 billion in the next 5 years,” which would not be counterbalanced by the estimated $16 billion saved by preventing cirrhosis, HCC, and transplantations.

Therefore, “despite the cost-effectiveness of [novel] HCV treatments, our analysis shows that it is unaffordable at the current price,” Dr. Chhatwal and his associates said.

In the other study, funded primarily by CVS Health , researchers developed a discrete-event simulation model of the natural history and progression of liver disease in treatment-naive patients, categorized by whether they were infected with HCV genotype 1, 2, or 3. Several possible treatment regimens were considered for each genotype, and the SVR rates they were projected to attain were derived from those reported in clinical trials, said Mehdi Najafzadeh , Ph.D., of the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital and Harvard Medical School, Boston, and his associates.

“From a societal perspective, the newly approved PEG-free regimen of sofosbuvir-ledipasvir for 12 weeks could be very cost-effective relative to usual care (costing $12,825/QALY gained) for patients with HCV genotype 1.” This treatment proved to be the optimal strategy in the greatest number of simulations involving genotype 1.

Similarly, for genotype 3 the combination of sofosbuvir plus ledipasvir plus ribavirin for 12 weeks cost $73,000/QALY gained, compared with usual care. This also represents “relatively good value.” However, for genotype 2 the most cost-effective novel therapy, sofosbuvir-ribavirin, was $110,168/QALY gained, which is not considered cost-effective, Dr. Najafzadeh and his associates said (Ann. Intern. Med. 2015 March 17 [ doi:10.7326;M14-1152 ]). Again, an important caveat to these findings was that, at their current prices, the cost of these drugs were not outweighed by the savings that accrued from preventing the complications of HCV. And “regardless of the cost-effectiveness of novel HCV treatments, there is considerable concern that their very high prices could substantially increase short-term overall drug spending for many public and private payers,” the investigators noted.

However, the fact that these regimens don’t reduce health care costs “is an exceptionally high bar” to hold them to – one that “is generally not expected when evaluating whether a new strategy represents good value for the money,” they added.