The following is a guest post by Allan Joseph, a medical student at the Warren Alpert Medical School of Brown University and TIE research assistant. You can follow Allan on Twitter: @allanmjoseph. Links to Allan’s previous posts on hepatitis C can be found here, a post that also contains a glossary of terms.
In the months since my summer 2014 series on hepatitis C (HCV) and the drug sofosbuvir (better known by its trade name, Sovaldi), researchers have continued to pump out studies examining HCV treatment. Since much of that research has implications for policy and public health, I thought I’d do a roundup of some of it, organized by the themes that have come out. Let’s jump right in:
Patients co-infected with HIV and HCV
HIV and HCV co-infection is a really big problem. Five million people worldwide have both infections, while 1 in every 3 HIV-positive patients in America has a chronic HCV infection. Moreover, co-infected patients are much more likely to progress to liver failure than patients monoinfected with HIV — in part because their treatment regimens are more complicated than monoinfected patients. All that is to say that sofosbuvir and its companions in the new wave of HCV drugs could make a big difference in the lives of co-infected patients — but until recently, we haven’t had any data on whether these drugs would work as well in co-infected patients as in the monoinfected.
The Lancet published a medium-sized trial of sofosbuvir and ribavirin in about 275 co-infected patients across Europe and Australia, reporting SVR rates of about 85-90% depending on the genotype. That’s just about as good as the trials of sofosbuvir in monoinfected patients that led to sofosbuvir’s approval. Around the same time, JAMA published two smaller trials (50 and 63 patients) of other treatment regimens in the coinfected — a ledipasvir-sofosbuvir combination marketed under the brand name Harvoni, and a multi-drug regimen consisting of ribavirin and the ombitasvir/paritaprevir/ritonavir/dasabuvir combination marketed under the brand name Viekira Pak. Both JAMA studies reported very high SVR rates — well over 90%, though both were small and did not contain a control group. (As a refresher, “SVR” stands for Sustained Virological Response, which is the absence of HCV genes in a patient’s blood 24 weeks after stopping treatment. It’s the proxy measurement for “cure,” but they’re not quite the same thing.)
The real importance here is that none of these regimens use peginterferon, the drug that made previous treatment so difficult to adhere to. Peginterferon was previously a mainstay of treatment, but it was less efficacious in the coinfected. Taken together, these studies suggest that the gap in efficacy is now a thing of the past. In fact, the accompanying editorial in JAMA points out that the most recent guidelines for treating HCV state explicitly that HIV-positive patients should be treated the same as monoinfected patients. That’s a big deal from a public-health perspective
Costs have always been the most controversial part of the new treatments for HCV, as I discussed at length in my summer 2014 series. Recently, Charles Ornstein shed light on how these costs have started to take shape — in the first year these new drugs have been on the market (not even a full year!), they accounted for $4.5 billion in Medicare Part D spending, most of which is from the federal government and, in turn, taxpayers.
On the academic side, the Annals of Internal Medicine published three new papers that attempt to estimate the cost-effectiveness of these new treatments. These papers rely on various simulation models that I’m far from an expert in, so I’ll let someone more qualified dissect their methods and assumptions. Taken together, the three papers suggest that these new drugs will increase healthcare spending by a significant amount, but that in most cases, the drugs are also so much better that they’re worth the extra spending. To put it in terms often used on TIE, the studies argue that the drugs are generally cost-effective, but not cost-saving. That’s essentially the conclusion I had arrived at last summer, with some strong caveats.
Interestingly, one of the Annals studies estimated that sofosbuvir might in fact be cost-saving from a societal perspective if it cost about 25% less than it currently does. There are, in fact, two forces that could make that happen. First, and more well-known, is the fact that various pharmacy-benefit managers are cutting deals with Gilead (maker of Harvoni and Sovaldi) and AbbVie (maker of Viekira Pak) exchanging first-line status for what are likely some significant discounts. Second, and perhaps lesser-known, is the idea that the drugs might be so effective that doctors could prescribe far shorter treatment plans, cutting prices down. The Lancet recently published a small proof-of-concept study suggesting that a three-drug regimen could result in 6-week courses of treatment rather than 12 (though the addition of a third drug would reduce cost-savings), and we’ve already known that the ledipasvir-sofosbuvir combination can be used for 8 weeks instead of 12. These aren’t perfect substitutions (they likely have higher relapse rates), but if further research confirms these findings, they might reduce costs nonetheless.
I could have put the last two studies I wanted to highlight under either of the categories above, so instead I decided to give them their own. The Lancet published the results of two Phase 2 clinical trials of a combination of two new drugs named grazoprevir and elbasvir, found here and here. If the studies’ results hold up in phase 3 trials (far from a given) that are scheduled to end in about 18 months, there will be another, about-equally-effective treatment option on the market within a few years. That has two implications — first, these drugs appear to also be effective in the co-infected, which has public-health implications as I outlined above. And second, these drugs are made by Merck, which might mean a third company will join Gilead and AbbVie in competing for market share in the HCV market. Though some time away, that too will have implications for costs in the long run.
Hepatitis C is a special case when it comes to pharmaceutical competition — and that’s a post to be written another time — but in this case, it appears that the competition won’t be slowing down anytime in the near future.