April 17, 2013

Simeprevir and Sofosbuvir Submitted to FDA — Clock Ticking on Boceprevir, Telaprevir, Even Interferon

Journal Watch Blogs

Paul E. Sax, MD is the Editor-in-Chief, Journal Watch HIV/AIDS Clinical Care, Clinical Director of the Division of Infectious Diseases at Brigham and Women's Hospital, and Professor of Medicine at Harvard Medical School.

Paul Sax • April 10th, 2013

Two weeks, two companies, two press releases, two future HCV drugs that begin with “S”:

  1. March 28, 2013: Janssen Research & Development announced that it has submitted a New Drug Application to the FDA seeking approval for simeprevir (TMC435), an investigational NS3/4A protease inhibitor, administered as a 150 mg capsule once daily with pegylated interferon and ribavirin for the treatment of genotype 1 chronic HCV in adult patients.
  2. April 8, 2013: Gilead Sciences announced that it has submitted a New Drug Application to the FDA for approval of sofosbuvir, a once-daily oral nucleotide analogue for the treatment of chronic HCV infection. The data submitted in this NDA support the use of sofosbuvir and ribavirin as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with ribavirin and pegylated interferon for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

For several years now, all clinicians who see patients with hepatitis C have been promising them better treatments “soon”, with admittedly little precision about exactly what this “soon” actually means.

But with these filings, we have a pretty good idea. It will be less than a year — maybe much less. Why is that?

  • The FDA has roughly 10 months to review these applications. (The exact timing is somewhere on the FDA web site, see if you can find it.)
  • These two drugs have looked pretty great in clinical studies to date.
  • The bar to leap over to be substantially better than current standard -of-care treatment for HCV isn’t exactly high — a fact that could get at least one drug, if not both, priority review and even more rapid approval.
  • One of my patients has joked that I’ve been saying “in a few years” for availability of better HCV treatment options for at least “a few years” now — so my time is up.

Of course, stuff could happen that holds up the approvals. A toxicity could arise that hasn’t been reported previously, or a tricky drug-drug interaction could crop up. Or the sun could explode.

But if these things don’t happen, then for patients with HCV genotypes 2 and 3, a non-interferon option looks like it’s right around the corner — sofosbuvir and ribavirin. For those with genotypes 1 and 4, a shortened, more effective, and all-round improved interferon-based regimen will arrive at the same time — pegylated interferon/ribavirin plus either simeprevir or sofosbuvir.

And even better, how about an off-label combination of these two new drugs as in this clinical study – in which case the interferon can be dropped entirely, right?

Let the choir sing out when that happens, and enjoy a hearty celebratory brunch at the famous Cambridge deli pictured above in honor of the new regimen.


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