Source: Gilead Sciences.
All of the market's chatter surrounding Gilead Sciences' (GILD +0.61%) and AbbVie's (ABBV 0.91%) hepatitis C drugs this past year may have you thinking that these companies have won the decades long battle against this tough-to-treat disease. However, a study released in September by the pharmacy benefit manager juggernaut CVS Health found that 8.1% of patients in drug plans it manages taking Gilead's Sovaldi quit taking their medication prior to completing the 12-week treatment schedule. That discontinuation rate was quadruple the rate observed during clinical trials and reinforces just how badly patients still need new hepatitis C treatment options.http://www.cvshealth.com/sites/default/files/hepatitisCutilization.pdf
Improving the improvements
There's absolutely no doubt in my mind that the FDA's December 2013 approval of Sovaldi was a game-changing advance in patient treatment.
A decade ago, patients were treated with a cocktail comprising side effect-laden peginterferon and ribavirin that offered coin-flip cure rates. The 48-week treatment course was so difficult to stick with that during clinical trials a whopping 27% of patients stopped taking their medicine prior to completing the regimen.
The FDA's 2011 approval of Vertex Pharmaceuticals' Incivek improved cure rates to 80% and cut treatment duration to 24 weeks; however, since peginterferon and ribavirin were still required alongside Incivek, nonadherence rates remained a big problem.
As a result, doctors and patients applauded the launch of Sovaldi, an oral drug that delivers 90%-plus cure rates over a 12-week treatment schedule. However, while Sovaldi casts aside the use of peginterferon for many patients, ribavirin remains necessary. According to CVS Health, 9% of patients taking that combination discontinued treatment before completing the 12-week treatment period.
Welcoming the next generation
This past October, the hepatitis C community welcomed Gilead Sciences' second-generation hepatitis C drug Harvoni.
Harvoni is a single tablet combination pill that includes Sovaldi and ledipasvir, a drug that targets the NS5A protein that plays an important role in hepatitis C's viral replication. In clinical trials, Harvoni's once-daily pill delivered cure rates in the mid-to-high 90% range over both an eight-week and a 12-week treatment period. Importantly, thanks to Harvoni not requiring treatment with peginterferon and ribavirin, the number of people who dropped out of its trials totaled less than 1%.
Source: AbbVie
In December, the FDA also approved AbbVie's competing hepatitis C drug, Viekira Pak. Viekira Pak is a cocktail of drugs delivered via up to four pills daily. In clinical trials, it delivered cure rates in the mid-90% range. However, the combination of a more onerous pill burden and the fact that Viekira Pak treatment still includes use of ribavirin in many patients, resulted in adherence rates below 90%.
Remaining work
Harvoni and Viekira Pak are only approved for use in genotype 1 patients, and, much like Sovaldi (and its predecessors), both remain far from perfect drugs.
With neither gaining FDA approval for use outside of genotype 1, and with AASLD treatment guidelines only recommending their use in genotype 1 and 4 patients, millions of patients globally must still rely on Sovaldi.
Additionally, while Harvoni posted far better adherence rates in clinical trials than did Viekira Pak, the real-world nonadherence rates for both drugs are likely to be higher than those achieved in these controlled settings.
Based on Sovaldi's real-world adherence rate, Harvoni's discontinuation rate could end up in the middle single-digits and Viekira Pak's nonadherence rate could also grow significantly above the numbers observed in trials. If so, that could mean the treatments still come up short for millions of people.
Looking ahead
Considerable advances still need to be made in hepatitis C treatment if we hope to effectively cure every one of the estimated 150 million people with the disease globally. Ultimately, the Holy Grail of hepatitis C treatment is delivering 100% functional cure rates across all genotypes in as little time as possible. We've made huge inroads toward achieving that lofty goal, but there is still a significant unmet need for new therapies. Investors, doctors, and patients should remain focused on hepatitis C research and development pipelines.
