Both Simeprevir and Sofosbuvir Likely Approved by 2014 —Clinical/Ethical/Pharmacoeconomic Dilemmas Loom

Paul Sax • June 11th, 2013

As expected, simeprevir, and now also sofosbuvir, are being given “priority review” by the FDA.

With the 6-month rule under the Prescription Drug User Fee Act — usually just said as “pah-DOOF-ah” — that means there’s a good chance we’ll have both of these anti-HCV drugs some time in late 2013.

Which also means HCV treaters will soon face a major dilemma regarding management of HCV genotype 1.

For those not following this field closely, here’s the deal:

• If approved, both simeprevir and sofosbuvir will be indicated for treatment of HCV genotype 1, but only in combination with pegylated interferon/ribavirin. (Sofosbuvir approval is also expected for genotype 2/3, just with ribavirin.)
• Both will be one pill once daily. Simple!
• Both will cost a lot. Reminder, a course of telaprevir is $50,000, and these two new drugs are better.
• The interim results of the COSMOS study, presented at CROI this year, showed a >90% cure rate in 80 prior null responders (no cirrhosis) who received simeprevir and sofosbuvir together for 12 or 24 weeks, with and without ribavirin. There was no interferon in this study.  (The full slide set of the presentation is on NATAP.)

So if these two drugs are both approved as expected, one could easily make the case that the best treatment for HCV genotype 1 — in terms of efficacy, safety, tolerability, pretty much everything except drug-drug interactions and cost — will be the COSMOS regimen of simeprevir and sofosbuvir, with or without ribavirin. And emphatically without interferon.

And that, my dear friends, is off-label use.

So let’s get inside the head of the various players in this potential drama to imagine what they’ll be thinking.

It’s January, 2014, and a patient previously treated with interferon/ribavirin for 48 weeks who relapsed is coming in to review his new treatment options. Here are some potential thought balloons:

Patient: I just want what works best. Sure would be nice to avoid all those nasty interferon side effects I had the last time I was treated.
Provider: I’d like to prescribe simeprevir plus sofosbuvir to avoid all those nasty interferon side effects the last time he was treated. I have some uncertainty about whether to include ribavirin, and whether to treat for 12 or 24 weeks.
Provider’s RN/PA/NP/PharmD who manages all HCV treatment:  Sure will be nice to avoid all those nasty interferon side effects that happened the last time he was treated.
Patient’s insurance company: Both simeprevir and sofosbuvir?  Two DAAs? You gotta be kidding me — we’re not paying since the regimen is not FDA-approved. Here’s a toll-free number for you to call and argue the case, but the estimated hold time is longer (by a factor of 10) than trying to call an airline to get a flight changed during a blizzard.
Phamaceutical company: We invested a gazillion dollars to bring these drugs to market. Plus, if you consider the net societal savings by curing HCV and avoiding cirrhosis, liver failure, hepatocellular carcinoma, liver transplants, secondary transmission etc, the price is justified.
Activists:  The best treatment should be available for all!
Academic MD expert who has been asked to comment, but isn’t actually seeing this patient (or any patient) today because he/she is writing grants and papers, or traveling:  The sample size of the COSMOS study is too small to influence clinical practice.

Of course, this will all settle out once there are multiple non-interferon HCV treatment options out there.

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