Hepatitis C Drug Pricing Continues to Evolve

Recent research revealed a positive relationship between the proportion of hepatitis C virus (HCV) patients who achieve sustained viral response (SVR) and the pricing of the HCV drug regimen.

For a study published in PLOS ONE, researchers classified the different treatment regimens into 5 steps: interferon-α (IFN-α) monotherapy; interferon-α associated with ribavirin (RBV); pegylated Interferon-α (pegIFN-α) associated with ribavirin; first direct-acting antivirals (DAA) associated with pegylated Interferon-α and ribavirin; and second wave DAAs, such as nucleotidic and non-nucleosidic polymerase inhibitors, NS5A inhibitors, more serine protease inhibitors that are or are not associated with pegylated Interferon-α and ribavirin.

All phase 3 randomized clinical trials (RCT) that enrolled previously treated chronic HCV genotype 1 patients and tested drugs that were approved and marketed in Switzerland from January 1, 1997, to July 31, 2015, were selected for the study.

The SVR rate reported in the studies at the time of the Swissmedic marketing authorization request was used. The drug dosage, price, and duration were based on the recommended Swissmedic guidelines for HCV genotype 1 treatment-naïve patients during the study period.

For older drug regimens not listed in the database, researchers used data from the FDA. Since IFN-α data was not in either of the databases, researchers contacted pharmaceutical companies to find which published studies contributed to drug marketing.

In the study, SVR was defined as undetectable HCV RNA in the serum 12 weeks after the end of treatment for DAA-based regimens and 24 weeks for IFN-α based regimens. Since market prices for IFN-α, pegIFN-α and RBV have changed throughout the past 25 years, researchers controlled for inflammation using the market price of IFN-α for step 1 in 1997, and adjusted it by the inflation rate for both US and Swiss pricing.

In steps 2 and 3, researchers used January 2003 prices for IFN-α, pegIFN-α and RBV, which were adjusted by the inflation rate. For the first and second waves of DAAs in step 4 and 5, the launching market price and current price of pegIFN-α and RBV were used without adjusting for inflation.

Typically, RBV administration is weight-adapted; however, researchers arbitrarily considered a standard daily dose of 1000 mg for all recipients. In order to assess the HCV therapy pricing model, researchers used 2 methods.

First, they plotted the costs per treatment of the 22 regimens against the rate of SVR in the United States and Switzerland. The scatter diagram ended up indicating a linear relationship, so researchers tested the linear correlation between the 2 variables by the standard Pearson correlation coefficient and R² of a bivariate linear regression.

In the second method, researchers measured the mean and standard deviation of the costs, and costs per SVR for the 5 HCV treatment steps. The Eviews 8 software (QMS) was used for the statistical analysis and 22 RCTs were included in the study that comprised a total of 5900 patients.

Two clinical trials were included for the IFN-α monotherapy step, consisting of 476 patients. For the association between IFN-α and RBV, the trials consisted of 613 patients. Step 3 included 6 studies for the association between pegIFN-α and RBV, including 1316 patients.

For the first DAAs, there were 6 studies with 1992 patients and 6 for newer DAAs that included 1503 patients.

The results of the study showed a steady cost increase paralleling the increase in the SVR rate for each treatment step. Furthermore, from step 4 and on, the treatment durations were shortened to 24 weeks or 12 weeks, and pegIFN-α could be omitted from most of the regimens.

Additionally, the findings suggest there is a positive linear association between SVR and the cost of HCV treatment regimens. For the incremental costs per additional percentage point of SVR, it was estimated as $597.14 USD in Switzerland and $1063.81 in the United States.

The results of the study confirmed a close association between the mean SVR rate and the mean costs per treatment step. The findings suggest a relatively stable ratio of costs per cured patient over time, and results in a strong positive correlation between the HCV cure rate and costs per treatment.

This indicates the pharmaceutical companies use a value-based pricing model for HCV treatments.

The study concluded that the significant budget impact of these new agents remain a struggle for health care systems, caused by the high efficacy of the DAAs and the willingness of insurers to provide coverage.