simprevir sofosbuvir cohort 2 svr4 results

[johnny679]

Hope these results cannot be  ignored if same svr in 8 weeks  . if of course they remain the same a further 8 weeks the same  in first cohort svr4 and svr8 were the same , look great , if people with advanced fibrosis are being cured with this combination and they will be most probably be available in  2 or 3 months why the hell should people be made to wait another year for gilead and abbvie to release there combos .
Close to a 100 % svr

STOCKHOLM, Aug 28, 2013 (BUSINESS WIRE) -- ---- Once-daily simeprevir and sofosbuvir with or without ribavirin was generally safe and well tolerated

Regulatory news:

Medivir AB (omx:MVIR) (sto:MVIR-B) today announced interim results from the second Cohort in the ongoing COSMOS study evaluating a once daily combination of simeprevir and sofosbuvir in hard to cure hepatitis C (HCV) patients.

SVR4 results from the 12 week arms of Cohort 2, including treatment naive or previous null responder HCV patients all with METAVIR score F3-F4 were reported. Treatment for 12 weeks with simeprevir and sofosbuvir, with or without ribavirin, led to SVR4 rates of 96% and 100%, respectively.

Interim results from Cohort 1 of the COSMOS study, which include only prior null responder HCV patients (METAVIR F0-F2) have been reported earlier and demonstrated SVR8 rates of 96% and 93% after 12 weeks treatment simeprevir and sofosbuvir with and without ribavirin, respectively.

"The high SVR rates seen in genotype 1 prior null responders and treatment-naive patients with advanced liver disease, in the COSMOS study and the safety profile of the combination are highly encouraging. We look forward to the final results of this study in difficult to cure patients." says Charlotte Edenius, EVP Development, Medivir AB.

COSMOS - Study Design

COSMOS is a randomized, open label, phase IIa clinical trial evaluating a once-daily combination of the HCV protease inhibitor simeprevir and the nucleotide sofosbuvir with and without ribavirin (RBV) for 12 and 24 weeks. Cohort 1 (n=80) evaluates prior null responder genotype 1 hepatitis C (HCV) patients with METAVIR scores F0-F2 and Cohort 2 (n=87) evaluates prior null responder and treatment-naive genotype 1 hepatitis C patients with METAVIR scores F3-F4. The METAVIR score is used to quantify the degree of inflammation and fibrosis of the liver. Liver fibrosis is scored on a four-point scale.

At the time of the interim analysis, SVR4 results were available for all patients (n=41) in the 12 week arms of Cohort 2. In this Cohort, 78.2% of patients had GT1a subtype with 40% of those having a Q80K baseline polymorphism, 79.3% had IL28B CT or TT genotype, 47.1% had Metavir score F4 (cirrhosis) and 54.0% were prior null responders.

In the previously reported Cohort 1, 77.5% of the patients had GT1a subtype with 50% of those having a Q80K baseline polymorphism, 93.7%, had IL28B CT or TT genotype and 58.8% had METAVIR score F2.

COSMOS - Summary Interim Results: Efficacy

Efficacy results with 150 mg simeprevir (SMV) and 400 mg sofosbuvir (SOF) once daily for 12 weeks with or without ribavirin (RBV). Intent-to-treat (ITT) population.

[candyce1953]

Me too, I really want to see those results ( fingers crossed)

[ms maddie]

Almost done, Lynn.  Got five days of pills to go.  Then the real test begins.  Really anxious to see those SVR12 results from Cohort II of COSMOS though.  
Hope you are doing well on the tx.  Maddie

[flyinlynn]

Fantastic! Thanks for the updated info.

I am very interested in the final results of the Cosmos cohort 2 study as I am sure are many others.

How is your treatment going? for me 2 weeks down 10 to go.

Best wishes to all
Lynn

[ms maddie]

We will soon find out the final results of Cohort II of the Cosmos study.  
Tx naive/F-3-F4 and prior null-responders.

Final cohort 2 results (SVR12) of Cosmos study have been accepted for presentation at the European Association for the Study of the Liver (EASL) International Liver Congress 2014 on April 12.

There is going to be another study involving both drugs to take place in the US and Canada.

Study design
OPTIMIST-1
The first trial, called OPTIMIST-1 or TMC435HPC3017, is a phase III, open-label, randomized study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.
The combination will be administered once daily for 8 or 12 weeks in chronic HCV genotype 1 infected patients without cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 300 patients in the U.S. and Canada.

OPTIMIST-2
The second trial, called OPTIMIST-2 or TMC435HPC3018, is a phase III, open-label, single-arm study investigating the efficacy and safety of simeprevir 150 mg in combination with sofosbuvir 400 mg.

The combination will be administered once daily for 12 weeks in HCV genotype 1 infected patients with cirrhosis who are HCV treatment naïve or treatment experienced. This study will enroll approximately 100 patients in the U.S. and Canada.

Ribavirin will not be administered in the OPTIMIST trials. The primary efficacy endpoint in each study is the proportion of patients achieving sustained virologic response 12 weeks after the end of treatment (SVR12).

http://hepatitiscnewdrugs.blogspot.co.uk/2014/04/phase-3-trials-evaluating-simeprevir.html

[Pamelajean1]

Good advice Lynn! Right now I've got them on speed dial and we are all on first name basis. ;)
I'm in charge of MY health and have taken charge of this appeal....if denied it won't be for lack of trying.
My biggest challenge is that I haven't treated before so don't have that to 'prove intolerance'....still it's my preferred tx because it has the highest success rate and with the least amount of sx. If denied, it will make me elligable to apply direct to Gilead and I have folks on stand by with that. It's my mission and I don't give up easy.
Any way it goes, I will be an advocate to not let those of us fall between the cracks on this and be ignored....it just isn't right.
I'll get off my soapbox now lol! Thanks for your support!

[flyinlynn]

Hi Pamela
Good luck on your appeal I hope you have the same results I did. I did end up calling express scripts seemed they needed a new questionnaire done by my Dr. They faxed it to my doctors office and I called them to let them know to be on the look out for it. Next day in the later morning I called express scripts again to make sure they had the info. Fourtyfive mins on hold later I got a verbal approval and reference numbers to give to my Doctors office. Next day I had a message from my local speciality pharmacy wanting to set up delivery instructions. YAY!!!

So be the sqeeky wheel and get results!

Good luck
Lynn

[ms maddie]

I'm doing well...just hope UND continues forever once I'm done.  
I can't understand why you are being given such a hard time getting approval.  It's crazy!  Wish I could help.  You must be so frustrated.  Hopefully, you will hear something positive this week.
Maddie

[Pamelajean1]

Ms Lynn, I saw where you were finally approved...congrats!

Yep! I'm on my 2nd appeal. I can just about quote word for word the Cosmos study and the recommendations from AALSD. Great info!

Best of luck with tx....just think! You are on your way to being cured!!  

[Pamelajean1]

You're right and I haven't seen those either...the post prior to mine didn't include the results I posted though which is why I went ahead and posted. I keep looking for SVR 12 results....you'd think that would have been available what, by December 2013/January 2014?

Good 'seeing ya'...hope all is well. I'm still plugging along going thru appeals for the 'off label'.

[ms maddie]

Thx Pamelajean.  I know about the interim results of cohort II of the cosmos trial but I was wondering if the final results of cohort II were ever published anywhere (that is svr 12 not only svr 4 of cohort II).  So far, I haven't seen anything.

[flyinlynn]

There are a number of people here who are on this combo. I just picked up Sovaldi and Olysio yesterday and will be starting next Wednesday. Just 2 pills a day. The problem is it is difficult to get approval as the usage is off label so it takes some patience dealing with your insurance company. I qualify because I have GT 1a and have been a null responder to 3 rounds with initially intron Alpha 3 shots a week and then two tries with interferon with ribaviron. I also have cirrhosis and have had esophageal varicies grade 3 that required banding.

See the AASLD treatment guidelines for recommended treatment protocols

http://www.hcvguidelines.org/sites/default/files/full_report.pdf

Good luck
Lynn

[Pamelajean1]

Cosmos study.....

In cohort 2, 78 percent of patients had GT1a subtype with 40 percent of those having baseline Q80K polymorphism. Fifty-six percent had IL28B CT genotype, 23 percent had IL28B TT genotype, 47 percent had METAVIR score F4 (cirrhosis) and 54 percent were prior null responders.

COSMOS – Efficacy Summary
In cohort 1, the SVR12 rate was 93 percent in genotype 1 null-responder patients with METAVIR scores of F0-F2 treated with simeprevir and sofosbuvir for either 12 or 24 weeks.

In an interim analysis of cohort 2, the SVR4 rate was 100 percent in both genotype 1 treatment-naive patients and prior null-responder patients with METAVIR scores of F3-F4 treated with simeprevir and sofosbuvir for 12 weeks.

In a pooled analysis of the 12-week treatment arms in cohorts 1 and 2, SVR4 was achieved among patients treated with simeprevir and sofosbuvir with or without ribavirin, in 96 percent of patients with IL28B non-CC genotype, 91 and 100 percent of patients with a METAVIR score of F4, respectively, and 95 percent of prior null responders.

All patients who completed treatment were HCV RNA undetectable at end of treatment and there were no viral breakthroughs in either cohort 1 or 2. The COSMOS study interim results show no benefit from adding ribavirin to simeprevir and sofosbuvir in this difficult to treat groups of hepatitis C patients and that 12 week treatment may confer similar clinical benefit to 24 week treatment. - See more at: http://hepatitiscnewdrugresearch.com/sofosbuvirgs7977simeprevirtmc435.html#sthash.3RUNA2IA.dpuf

[ms maddie]

Has anyone seen any Cohort II info for the SVR 12 results?  I would think there should be some info by now.  This article was from last August.

[johnny679]

You are correct will be difficult to find a payer , and the 2 together would probably cost $ 150 000 small trial cohort 1 did well , cohort 2 seems to be a similar result . Its a shame though that something so close to being released could cure most of us will not be offered to people and most will need to wait for sofosbuvir/ledipasvir at best late next year .
One doctor told me that the sofosbuvir/ledipasvir combo will probably cost close to $ 70 000 to $ 90 000 usd , expensive tablets close to $ 1000 per tablet

[Willy50]

You'll notice this was not a large trial.

http://www.hepatitiscnewdrugresearch.com/sofosbuvirgs7977simeprevirtmc435.html

So it is a little hard to be certain, but generally the combo should be roughly equal to the drugs in trials right now. (from gilead or abbvie)

The issue will be;
Who is paying for the treatments? Will an insurance company reimburse the patient?  What will the ala carte costs be?

Will doctors prescribe the treatment even?  They may not be willing to order the drugs since they are not FDA approved together.

If you want/expect insurance to pay you may end up waiting for an approved TX
Please recall that when incivek and victrelis was approved many insurance companies initially balked at the extra cost for the TX.  Many patients were initially refused.

willy

[willbb]

Thanks for posting this.

Will