Gilead Sciences (GILD -1.22%) was the first to submit its highly anticipated hepatitis C virus (HCV) combination therapy to the FDA. Recently, Bristol-Myers Squibb (BMY -0.13%) earned a Breakthrough Therapy designation for its dual regimen, likely to compete with Gilead's. AbbVie (ABBV -0.75%), and Merck (MRK 0.88%) are also developing combination HCV treatments of their own, both with breakthrough designations.
Gilead's combo carries an enormous price tag, but America's largest pharmacy benefit manager Express Scripts (ESRX) has voiced its intent to curtail the pharmaceutical industry's pricing power. Here's a look at the competing therapies, and the expedited regulatory pathway that could result in several of them reaching the market at roughly the same time.
About the Breakthrough Therapy designation
The FDA has implemented expedited pathways in the past, but I don't think any has been as well defined as the Breakthrough Therapy designation. Implemented in 2012, the designation is reserved for targeted therapies that hit significant efficacy marks in early or mid-stage clinical trials. The nature of the condition must also be serious enough that patients are clearly willing to trade safety for speed, like HCV.
Without an expedited pathway, HCV therapies would likely need to provide data on the percent of patients surviving for several years after dosing. With the designation the FDA will work with the drug makers to define acceptable, shorter-term endpoints that should warrant approval. Of course, early approvals remain contingent on longer safety trials also designed in partnership with the agency. In the meantime, patients with unmet needs gain access to lifesaving new treatments.
Clash of the combos
From Gilead's perspective, the designation can erode the lead its HCV therapy had on its competitors. Gilead's Sovaldi as a single agent may have beat competitors to the US market in December last year, and last month in the EU, but it's the combination therapies that seem to have doctors warehousing patients by the thousands.
Fellow Foolish author Brian Orelli raised an important point recently. As a single agent, Sovaldi pills must be taken with pegylated interferon injections to be effective for genotype 1 (GT1) patients. Interferon injections produce very uncomfortable side effects. Sovaldi's first year on the market flying solo may be one of the most successful launches ever, but there are potentially millions of HCV patients that can wait for interferon and ribavirin free combination therapies. And that's where the trouble lies for Gilead in the years ahead.
In order to see a return on the $11 billion spent acquiring Sovaldi, Gilead has priced the single-agent therapy at $84,000 for a 12 week regimen in the US. If Express Scripts, America's largest pharmacy benefit manager, has its way, the combo will be far less expensive. During an interview with Bloomberg late last year, Express Scripts' Chief Medical Officer Steven Miller said his company would, "identify which drugs can be pitted against each other and make some really tough formulary decisions." Others may compete with Gilead on price, and the HCV combo field is getting more crowded each month.
A Breakthrough Therapy breakdown
AbbVie, Merck, and Bristol-Myers all have Breakthrough Therapy designated, HCV combinations in development. In a recent post I highlighted some data that makes AbbVie's and Merck's cocktails seem just as effective as Gilead's combination pill.
Since then Gilead has filed a New Drug Application with the FDA for the once-daily fixed-dose combination of ledipasvir and sofosbuvir for the treatment of GT1 HCV. On February 24, the FDA granted a Breakthrough Therapy designation to Bristol-Myers' daclatasvir and asunaprevir combination therapy for genotype 1b HCV patients. This is the second Breakthrough designation granted to Bristol-Myers' HCV combos.
While AbbVie and Gilead are widely expected to compete in order to remain on the Express Scripts formulary, Bristol-Myers' two drug combo was designated for the GT1b indication. Generally GT1b is more prevalent in Europe, so Gilead and AbbVie might not be competing with Bristol-Myers for a place on the Express Scripts formulary. At least not for a majority of GT1 patients.
Merck's two-pill HCV combination received its breakthrough designation last October for GT1 HCV. The company has remained quiet about the combo since reporting interim data at the American Association for the Study of Liver Diseases Meeting last November. During the latest earnings call, Merck's management mentioned its HCV program only in passing. The company's R&D head, Roger Perlmutter responsed to a direct question regarding the regimen by stating that data so far was not yet ideal. I'll keep my eyes open for more from the company. For now it doesn't seem that Merck is willing to enter the ring with AbbVie, Gilead, and Bristol-Myers just yet.
There may be three other HCV combination therapies in development with breakthrough designations, but for now it seems Gilead needs to concern itself with just one, AbbVie's. We can nitpick over the data, but the opinion that matters is that of major payers, like Express Scripts.
The late stage data from AbbVie and Gilead are outstanding, and Merck doesn't seem like it's willing to compete with them. If Bristol-Myers' combo's designation will only support an early approval for GT1b patients specifically, that should leave the majority of the US market to Gilead, and AbbVie. So far, it seems the only clear winner from that fight will be the payers.