I wonder if we will ever know the true % of relapse for those taking Sovaldi?
We will here that's for sure, id have to say we are a pretty good sample of folks from all corners of at least the States where it's available.
Maybe we start a sticky thread for those that have relapsed just to keep track and limit the commentary to just the answer.
Not my board but it would be better than all us fogheads trying to remember who did.
Just an idea
Huey said
Aug 28, 2014
Groupergetter wrote:
I wonder if we will ever know the true % of relapse for those taking Sovaldi?
Got a majic 8 ball?
Groupergetter said
Aug 28, 2014
I wonder if we will ever know the true % of relapse for those taking Sovaldi?
Tig said
Aug 28, 2014
Isis,
Since you're able to find hard to locate government databases, how about you take a look into those lost IRS emails? Keep an eye on the driveway for any dark sedans and people wearing dark sunglasses with earwig radiosets... JK!
Tig
mallani said
Aug 27, 2014
Hey Isiscat,
LOVE that letter to Gilead. I'm also impressed you were able to find it. Thanks.
Isiscat2011 said
Aug 27, 2014
Thank you, Matt. What a nice thing to say. The information available to the public, or even to the FDA for that matter, is limited.
As with any billion dollar industry pharma keeps its cards close to the vest. If only it wasn't about profits and brilliant scientists could all work together for the common good. Imagine what we could accomplish. Maybe someday, huh?
Matt Chris said
Aug 27, 2014
Hey Isiscat
Great work on digging up that NDA correspondence between the FDA & Gilead.
Public records are there to be found if we just know where to look.
Its outstanding to have a bright lawyer to help us navigate the FDA
Thanks matt
Huey said
Aug 27, 2014
What I think will happen, is Gilead will sell Sovaldi right before the dirt comes out, That is why they are in shush a hurry to get there 11 B back.
There will be lawsuits just like bend over America BOA but the culprits will have sold the outfit to a small S corp and leave them, the new owners with all the liability. They will file chapter 13 and taxpayers flip the bill.
Isiscat2011 said
Aug 27, 2014
Gator Man wrote:
It seems to me that we are near a 100% SVR rate if the right DAA combos and Tx duration are tailored to the specific needs of the patients. On the other hand, some of us were/are not in a position to wait for better clinical data and have to treat with the information available.
This describes the situation in a nutshell. Aahhhh.......to be an F-1 and have the luxury of time.
Having said that, the FDA needs to sit on Gilead with a bit more conviction to get some answers. It lets these guys get away with practically anything.
And, alas, we are the test bunnies. :)
P.S. This assumes the new DAAs are capable of eliminating the RAVs problem. The other possibility is that there is no eliminating them in some people.... the super-strain emerges. An awful thought.
-- Edited by Isiscat2011 on Wednesday 27th of August 2014 03:31:31 PM
Isiscat2011 said
Aug 27, 2014
mallani wrote:
Now, we need to know whether Daclatasvir and/or Ledipasvir are active against the RAV's described. Actually, we need a complete list of RAV's with responses to different DAA's, including antiproteases like MK-5172. Also we need to know the expected lifespan of these RAV's- it wouldn't help to reuse Sovaldi if these are still present. That's the way to develop a 'superbug' strain of the virus. Ah, so much to learn.
The FDA sent a letter instructing Gilead to determine the phenotypic susceptibility of Sovaldi against the following NS5B substitutions:
This doesn't give us the answers but it indicates that the FDA is aware of the RAVs problem and wants to take a closer look. The FDA instructed Gilead to file its findings by August, 2014. Hopefully, Gilead will also disclose how effective Ledipasvir is at defeating these substitutions.
Gator Man said
Aug 27, 2014
Isiscat2011 wrote:
mallani wrote:
I wish Gilead would come clean and release all their data on Sovaldi relapses.
The polymorphisms described should be cleaned up by the extra drugs. Extending treatment time may help with cirrhotics, who need the extra perfusion/exposure to drugs.
...
There is clearly a need for additional studies on hard to treat groups: cirrhotics, relapsers and RAV's, and particularly patients that have more than one of these complications. We also have limited data on Riba's effectiveness with various DAA combos and whether the Sx are worth dealing with versus any benefit. You are absolutely correct Malcolm, we need to get away from the one size fits all approach to Tx. It seems to me that we are near a 100% SVR rate if the right DAA combos and Tx duration are tailored to the specific needs of the patients. On the other hand, some of us were/are not in a position to wait for better clinical data and have to treat with the information available. My Tx decision was based entirely on incomplete COSMOS data. Length of Tx and the inclusion of Riba were decisions based more on getting insurance approval than clinical trial results. Limited trial results were in part based on Gilead's lack of cooperation with using Olysio with Solvaldi for more studies, despite urging from the FDA.
mallani said
Aug 27, 2014
I'm assuming that the article in Hepatology was referring to treatment with Sovaldi with Riba/ +or - Interferon.
The polymorphisms described should be cleaned up by the extra drugs. Extending treatment time may help with cirrhotics, who need the extra perfusion/exposure to drugs.
With an extra DAA added to Sovaldi, it would be hoped the extra DAA could handle these polymorphisms. Now, we need to know whether Daclatasvir and/or Ledipasvir are active against the RAV's described. Actually, we need a complete list of RAV's with responses to different DAA's, including antiproteases like MK-5172. Also we need to know the expected lifespan of these RAV's- it wouldn't help to reuse Sovaldi if these are still present. That's the way to develop a 'superbug' strain of the virus. Ah, so much to learn.
Matt Chris said
Aug 27, 2014
Thanks Wayne
I read this also, but we all should understand that beating HCV has never had its successes in a mono mode, beating HCV requires multiple tier attack with a minimum of two or more agents to box in and control the polymorphisms.
Isiscat one reason that Gilead extended treatment was a early trialist that had developed Rav's at the end of a 12 week treatment. Gilead next put him back on extended treatment and he cleared after the treatment. Seems like Gilead is not really sure or willing to reveal what they know or should I say what they don't know. If the percent of possible relapse is 2%-4% they are likely still in a good place, but time will tell.
matt
-- Edited by Matt Chris on Wednesday 27th of August 2014 06:02:50 AM
-- Edited by Matt Chris on Wednesday 27th of August 2014 06:03:50 AM
Isiscat2011 said
Aug 27, 2014
mallani wrote:
I wish Gilead would come clean and release all their data on Sovaldi relapses.
YES. Can I get an AMEN?
So, extending tx wouldn't help once the Sovaldi created RAVs show up?
-- Edited by Isiscat2011 on Wednesday 27th of August 2014 05:19:35 AM
mallani said
Aug 27, 2014
Hi Wayne,
Thanks for posting this. It confirms my comments from Feb 16th. in my '' Understanding Sovaldi' post.
I wish Gilead would come clean and release all their data on Sovaldi relapses.
Thanks for posting this, Wayne. Do you know if the resistance problem can be mitigated (or eradicated) by increasing the tx duration or would that not make any difference?
OldenSlow said
Aug 26, 2014
"SOF has a high barrier to resistance; however, low frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic HCV infection."
We will here that's for sure, id have to say we are a pretty good sample of folks from all corners of at least the States where it's available.
Maybe we start a sticky thread for those that have relapsed just to keep track and limit the commentary to just the answer.
Not my board but it would be better than all us fogheads trying to remember who did.
Just an idea
Got a majic 8 ball?
I wonder if we will ever know the true % of relapse for those taking Sovaldi?
Isis,
Since you're able to find hard to locate government databases, how about you take a look into those lost IRS emails? Keep an eye on the driveway for any dark sedans and people wearing dark sunglasses with earwig radiosets... JK!
Tig
Hey Isiscat,
LOVE that letter to Gilead. I'm also impressed you were able to find it. Thanks.
Thank you, Matt. What a nice thing to say. The information available to the public, or even to the FDA for that matter, is limited.
As with any billion dollar industry pharma keeps its cards close to the vest. If only it wasn't about profits and brilliant scientists could all work together for the common good. Imagine what we could accomplish. Maybe someday, huh?
Hey Isiscat
Great work on digging up that NDA correspondence between the FDA & Gilead.
Public records are there to be found if we just know where to look.
Its outstanding to have a bright lawyer to help us navigate the FDA
Thanks matt
What I think will happen, is Gilead will sell Sovaldi right before the dirt comes out, That is why they are in shush a hurry to get there 11 B back.
There will be lawsuits just like bend over America BOA but the culprits will have sold the outfit to a small S corp and leave them, the new owners with all the liability. They will file chapter 13 and taxpayers flip the bill.
This describes the situation in a nutshell. Aahhhh.......to be an F-1 and have the luxury of time.
Having said that, the FDA needs to sit on Gilead with a bit more conviction to get some answers. It lets these guys get away with practically anything.
And, alas, we are the test bunnies. :)
P.S. This assumes the new DAAs are capable of eliminating the RAVs problem. The other possibility is that there is no eliminating them in some people.... the super-strain emerges. An awful thought.
-- Edited by Isiscat2011 on Wednesday 27th of August 2014 03:31:31 PM
The FDA sent a letter instructing Gilead to determine the phenotypic susceptibility of Sovaldi against the following NS5B substitutions:
Genotype 1a:
L159F
L159F + L320F
LI59F + C316N
C316N, H, and F
L320F, S282R, and L320F + S282R
D61G
D61G + N62H, D and N
___________________________________
Genotype 1b
L159F
L159F+L320F
L159F+C316N
C316N, H, and F
E440G
____________________________________
Genotype 2b
L159F
L159F+L320F
L159F+C316N
______________________________________________
Genotype 3a
L159F
L159F+L320F
L159F+C316N
K211R
V321A
P540L
TS42A
http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2013/204671Orig1s000ltr.pdf __________________________________________________
This doesn't give us the answers but it indicates that the FDA is aware of the RAVs problem and wants to take a closer look. The FDA instructed Gilead to file its findings by August, 2014. Hopefully, Gilead will also disclose how effective Ledipasvir is at defeating these substitutions.
...
There is clearly a need for additional studies on hard to treat groups: cirrhotics, relapsers and RAV's, and particularly patients that have more than one of these complications. We also have limited data on Riba's effectiveness with various DAA combos and whether the Sx are worth dealing with versus any benefit. You are absolutely correct Malcolm, we need to get away from the one size fits all approach to Tx. It seems to me that we are near a 100% SVR rate if the right DAA combos and Tx duration are tailored to the specific needs of the patients. On the other hand, some of us were/are not in a position to wait for better clinical data and have to treat with the information available. My Tx decision was based entirely on incomplete COSMOS data. Length of Tx and the inclusion of Riba were decisions based more on getting insurance approval than clinical trial results. Limited trial results were in part based on Gilead's lack of cooperation with using Olysio with Solvaldi for more studies, despite urging from the FDA.
I'm assuming that the article in Hepatology was referring to treatment with Sovaldi with Riba/ +or - Interferon.
The polymorphisms described should be cleaned up by the extra drugs. Extending treatment time may help with cirrhotics, who need the extra perfusion/exposure to drugs.
With an extra DAA added to Sovaldi, it would be hoped the extra DAA could handle these polymorphisms. Now, we need to know whether Daclatasvir and/or Ledipasvir are active against the RAV's described. Actually, we need a complete list of RAV's with responses to different DAA's, including antiproteases like MK-5172. Also we need to know the expected lifespan of these RAV's- it wouldn't help to reuse Sovaldi if these are still present. That's the way to develop a 'superbug' strain of the virus. Ah, so much to learn.
Thanks Wayne
I read this also, but we all should understand that beating HCV has never had its successes in a mono mode, beating HCV requires multiple tier attack with a minimum of two or more agents to box in and control the polymorphisms.
Isiscat one reason that Gilead extended treatment was a early trialist that had developed Rav's at the end of a 12 week treatment. Gilead next put him back on extended treatment and he cleared after the treatment. Seems like Gilead is not really sure or willing to reveal what they know or should I say what they don't know. If the percent of possible relapse is 2%-4% they are likely still in a good place, but time will tell.
matt
-- Edited by Matt Chris on Wednesday 27th of August 2014 06:02:50 AM
-- Edited by Matt Chris on Wednesday 27th of August 2014 06:03:50 AM
YES. Can I get an AMEN?
So, extending tx wouldn't help once the Sovaldi created RAVs show up?
-- Edited by Isiscat2011 on Wednesday 27th of August 2014 05:19:35 AM
Hi Wayne,
Thanks for posting this. It confirms my comments from Feb 16th. in my '' Understanding Sovaldi' post.
I wish Gilead would come clean and release all their data on Sovaldi relapses.
http://hepcfriends.activeboard.com/t56748030/understanding-sovaldi/
Thanks for posting this, Wayne. Do you know if the resistance problem can be mitigated (or eradicated) by increasing the tx duration or would that not make any difference?
"SOF has a high barrier to resistance; however, low frequency NS5B substitutions associated with treatment failure were identified that may contribute to resistance of this important drug for chronic HCV infection."
http://hepatitiscnewdrugs.blogspot.com/2014/08/clinical-evidence-and-bioinformatics.html