June 11th, 2013

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

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.

I’m an optimist.

20 Responses to “Both Simeprevir and Sofosbuvir Likely Approved by 2014 — Clinical/Ethical/Pharmacoeconomic Dilemmas Loom”

  1. Abhijeet Guha says:


    It would be heartening to know that something good is coming out for this disease (Hep C) , but is there any preliminary estimation on the cost of Sofosbuvir when it is out in 2014, and also if it will come in the early 2014 in the market. Please do let us know.

    Thanks for this great info and all the efforts that you have put into.

    Warm Regards,
    Abhijeet Guha

  2. Ron A. says:

    After seeing a liver specialist in Miami it appears that I will be the perfect candidate for taking both drugs simultaneously without ribavirin or interferon. His major concern is how am I going to get the insurance companies to pay for this. it is the only viable solution that I have because of the side effects with the other drugs and current therapy.

  3. awani srivastava says:

    If the cost of the new anti HCV drugs are going to be >$50,000/ per course, the patients from poor countries will be deprived of it. Insurance companies may not pay the inflated bills and many patients may not be able to get the benefit of the research molecule. Pricing is one of the important aspects of therapy in poor countries. Largest number of patients who may require this drug is in the developing and poor countries. This must be considered while putting the price tag by the manufacturers

  4. Anonymous says:

    Finding I had HCV the end of 1999, I was told I was a perfect candidate for ribavirin interferon treatment. It seemed to be helping, leaving me with chronic anemia and fatigue with flu like symptoms for over a year. In 2005 I tried the rivavirin pegalated interferon with the same results. HCV has chronically effected my liver along with other vital organs like the kidneys, heart and pancreas. I am now on disability. A transplant is hardly an option when you have a high viral load since anti rejection medication causes a weakened immune system. I am so thankful there may be another treatment that will be available for us less fortunate and have such little time. I thank all of you who are helping make this new treatment available giving this person hope there will be a future.

  5. Anonymous says:

    It would be extremely helpful if you could advise readers as to how to lobby the FDA for release of both medications as a tandem treatment option. I just turned 60, have genotype 1 and need something like the combo treatment. How do we speed this along? Thanks!

  6. Stephenie Drew says:

    My daughter n law was just diagnosed with acute Hep C we think she contact this from the fertility clinic in South Jersey, from not sterilizing properly. She has a heart condition has had it since she was born surgery at Deborah Hospital when she was 3. They want to put her on interferon but the side affects are so bad and could damage her heart more. I read about the drug Sofosbuvir, we are interested in this drug for the less side affects we have a three year old grandson who needs his Mom. She lost her mother due to lung cancer. If this medication has passed all trials I hope that can get it to the general public. Stephenie Drew

  7. Liz says:

    My hubs has HCV and is a transplant patient, did 84 weeks of Interferon/Ribavirin and relapsed within weeks. He is an excellent candidate for the Sofosbuvir, with Interferon/Ribavirin…we already know what that will cost us—holy cow, another $50K for the sofosbuvir? Well, that’s life. Already out over $150K for the TP and tx post TP. Getting tired of this! But looking fwd to some hope with the sofosbuvir, if he can get it.

  8. Ron Schmitz says:

    I wonder if meficare with a supplement will covrr the drug costs.

  9. nadia says:

    Happy for my mother. Thank you tjank you

  10. Frank says:

    I live in Thailand. I’ve been told that it could take 3-5 years for Sofosbuvir to be approved for use here. I was wondering if you had any information on what other countries other then the US the drug will be available in and the possibility of purchasing Sofosbuvir yourself direct from Gilead and arranging for the treatment to performed in your home country in combination with peg-interferon+RBV.

  11. nax says:

    It makes no difference if the new medicaments cure gut or are available, the most of people can not pay such terrible Prices and they continue to die every day. They DIE and DIE and DIE, millions die. But no one cares! I hate this world where only Money is important! Gilead and Janssen destroy our hopes! They are so avaricious, how can they good sleep and go to church and look in the eyes of people? They want to have 70000-90000$ for only one drug for 3 months!!! There is no metter for such prises only avaricious!

  12. Edwin says:

    I understand that companies put time, money and effort into developing these drugs and it makes sense for them to want to make their money back. The question is, who sets these prices for research and development ? Because whomever sets those prices is the real crook here. It’s like when you go get a $8 dollar cane at the hospital and they charge insurance the maximum allowed, which is $38. These prices that are set so high for r/d are the culprits in this disgusting game with peoples lives over money.

  13. Rileyann says:

    My consult today, 2/25/2014 with my hepatologist in the center where I have followed and tested for 13 months, discussed my options and will prescribe the combination of sofosbuvir and simeprevir. It’s been an 18 year battle and the better part of my working life diminished. I hope and pray for all those who know what suffering there is from delay to delay, just keep fighting, exercise, eat right and pray (if you believe that way).

  14. TIM MULLEN says:

    i have hcv 1a & 1b. i could not handle the interferon/ribavarin regimen 8 years ago. i do have some cirhossis. i wonder if the new 2 pill only combo will work for me. i will not do interferon/ribavarin again. i believe that is why my friend went downhill and died so quickly. that stuff is nasty. i was on it for 7 weeks and could just sense that it was affecting me in negative ways. i believe it is the culprit behind my balance and leg weakness issues that i didn’t have before using that tx. realistically, when will these new treatment be available to the common man that isn’t rich?

  15. kim toberer says:

    Dont have the cash to continue .100,000 wow takes me 3years to make that much . Let alone food rent etc. leaves my family .0 to live on But I have to have insurance…… to bad its no approved for this treatment , guess I will just have to die. Just doesnt make sense to me.

  16. M A EBRAHIM says:

    Relax very soon we will have generics from Asia
    We will never allow them to fleece the poor countries

  17. john Weaver says:

    I have been treated twice with interferon, ribavirin, the second protocol included Victrelis, a protease inhibitor. no detectable virus in just 2 weeks through the 12th week. In week 13 I was struck by a car and spent 2 months in ICU and Rehab. Virus came back. I live in the USA.
    Now my liver is cirrhotic and its just getting worse, my hematologist says to wait until next year 2015 for “the best bang for my buck”. I totally disagree. My insurance says they will pay for it and I’ll have just a $30.00 co-pay. OK by me for sure.
    Who can I contact to obtain Simeprevir and sofosbuvir so my U.S. primary physician can prescribe them “off label”?

  18. Kristen says:

    I started taking the sofosbuvir and simeprevir in combination almost two months ago. the hep c is unditaectable in my blood but i am not responding to the simeprevir. can anyone tell what that means?

    • john says:

      Kristen, let me be clear on your statements. You are currently or were taking the new antivirals. Does your treatment include Interferon? I am waiting for the sofobuvir and ledipasvir combination one a day pill boasting 100% cure rates for hep C1a . Including patients failed previous therapies w/ Interferon.
      Gilead filed New Drug Appl. 2/10/2014 and expects decision from FDA by 10/10/2014 – target action date . I am holding my breath for this regime. So does your therapy require interferon, if not who is supplying it?

  19. M.Sivakumar says:

    i am sivakumar i had C virus and i under gone liver transplant before 2 years. but still C viurs with in my Blood. good news for me and all c virus affected patients. Who are research they are all our ” God “. Pl advice when it will come to india and cost . once again thanks to all.

    Regards / Sivakumar.M

HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

Contributing Editor

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Infectious Diseases

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