How do we put pressure on Gilead/Bristol??

[UKgirl55]

That's my question because this just makes me sick!

http://hepatitiscresearchandnewsupdates.blogspot.com/2012/04/gilead-bristol-put-profits-ahead-of.html

[stef2011]

we are in similar situation with hbv cures but....russia has just put money and human trials finished in months for myracludex hbv cure so gilead came out with gs9620 (hbv and hcv) all of a sudden

so how to force them on market:
get funds from patients to move a small company to make the drugs where US patents have no meaning, you ll get the drugs on market in months.....

[kris235]

I am in the medical community.  This drug should be available late 2013. DDO we really believe all we read on the IN?

[Willy50]

As the natap link showed there was a difference in il-28 genetic marker response.  This is not definitive, but as I understand it there were two more presentations at EASL which suggested that the markers do in fact effect response, even w/ DDA combinations. (I believe from BI and from BMS)

In listening to a Gilead presentation, they really are not commenting on their plans w/ partnering w/ BMS.  Some of it is contingent upon a current obgoing trial, but Gilead repeatedly makes their case that GS-5885 is interchangeable to BMS Daclatasvir.  

They were very forthcoming in explaining that they were trying to speed and advance combining 7977 with 2 separate drugs they own.  They can't comment on what their talks would yield with the FDA in plans to advance the all Gilead combinations used to advanced all oral trials.

It looks like they are going to try a very small trial in nulls with 7977 + Riba+ GS5885.  If you recall they had a very small nulls trial w/ 7977 +RBV that cleared everybody, but all but about 10% relapsed.  In adding GS-5885 it is expected that the relapses will turn into SVR's, and possibly in 12 weeks.

I think that if people are being critical of Gilead, it is that the price that they paid for Pharmasett ends up determining their actions; they are forced to recoup their investment or face the rath of investors.  

It looks as though they are going to try to court the FDA and see if there is a way to bring the combination of 7977 w/ 5885 to a speedier path to approval, but one is mindful that it simply is unlikely that it would come as soon as with the partnership with BMS.  

In their investor presentation they suggested that the work done with the BMS compound daclatasvir is essentially transferable to GS5885, and they are hoping this will mean a more streamlines approval of the teaming; they dubbed the trial a phase 2/3, meaning kind of 2 phases rolled into one.  That seems like a kind of daring leap of faith, but the emphasis is on any method of streamlining approval.

There is still a question for me; what is all this going to cost?  If you knew what it would cost in 3 years maybe you would treat today.  : )  

Not all people need the best in class treatments to come to be cured.  It begins to look as though staging, genotype sub types and il-28 genetic markers could lead one to seek treatment sooner than awaiting for the best in class treatments to arrive.  

At least riba is generic; one thing is getting cheaper.  : )

willy

[SusieS2010]

Thanks so much for doing that reading. You have confirmed my thoughts. There are so many things to consider when looking at trial results. My doc always said you have to look at the intent to treat and not the results of clinical trials. I'm not ready to complain about Gilead just yet.

[nowhine]

A bit off topic on this thread although IL28B polymorphism testing is becoming an irrelevant  factor with regards to all oral DAA tx. This testing is a response predictor for INF/Riba tx. It is still a relevant factor for triple tx. It seems to me, since treatment naive patients have not treated yet, they will eventually fall into one of the catagories of cured, partial responder, null, or relapser when treating with INF/riba and/or triple. The fact that 100% of these folks achieved SVR4 with the Gilead/BMS is very encouraging for those in waiting.

[FaithforHealing]

If this were actually a rather benign story I would think Gilead would speak up and address the allegations that are being made that it's all about their greed. (Maybe that is no longer the terrible insult it once was and they don't feel the need to defend their reputation?)
They are not doing themselves any favors by not revealing their valid reason(s) for not moving forward with Bristol on Phase 3 (if it's not the money). Keeping silent is the red flag for me.

[Willy50]

The EASL results have not been in long.  I am not that up on things myself.  And so I did a little reading tonight.

=========================
http://hepatitiscresearchandnewsupdates.blogspot.co.uk/2012/04/easl-2012-all-oral-combination-of.html

I believe i also read that this group was comprised of a 44% il-28b CC genetic marker;  But 3 different arms with 3 different regimens, but each arm achieved a 100% SVR-4  I believe that 1/2 of the 88 participants were G-1 for a total of 44 total, and so the sub-sets of groups will be pretty small and subjective.  I'm not sure that you had enough cirrhotics/ null responders, etc, to draw much in conclusions.  No discontinuations due to sides it appears.
--------------------------------------------------

http://www.natap.org/2012/EASL/EASL_45.htm

"Why the disparity between the strong Electron results and weaker Quantum results using the same treatment regimen? Electron enrolled easier to treat patients -- 44% had the IL28B "CC" genetic variant of the hepatitis C virus which is known to respond better to treatment. By comparison, only 16% of the patients in the Quantum study carried the "CC" genetic variant."

This may mean that the results while 100% were in a statistically too small group, and that the il-28 predisposed it to success.
I think that it was exciting seeing the 100% SVR rate, but the outcome may not be quite so robust in larger trials.
----------------------------------------------------

I believe there is currently a trial collaboration between Gilead and BMS with null responders that is at approaching a month in., and so they may have a handle on a percentage of RVR's in nulls, or soon should.  I am not sure that given the size of the Electron study that one could conclude a lot about other factors which affect response and SVR rates.

It is a good start and given that some of the DDA's I have seen have been so-so, the collaboration seems to have great potential.

Anyway..... here is a little information. I'm not totally positive it is correct.  I had to shop for it; perhaps I made an error in transcribing or understanding;
Loooong day. : )

willy

[mdudley]

Excellent post...and frightening at the same time!  I hope people will not underestimate the power of the internet when it comes to signing the petition, posting it on facebook, twitter, etc..  Remember the Arab Spring?

http://www.thenational.ae/news/uae-news/facebook-and-twitter-key-to-arab-spring-uprisings-report

Facebook and Twitter key to Arab Spring uprisings: report
the "Arab Spring"

Social media – its rise and its new activist uses – have “played a critical role in mobilisation, empowerment, shaping opinions and influencing change,” the report said.

Perhaps this could be the start of the "Hepper Spring"!  Petition link below:

http://www.change.org/petitions/gilead-sciences-a-phase-iii-collaboration-for-the-treatment-of-hepatitis-c

Heppers Unite!

[SusieS2010]

Your above post was excellent. Your point about the people with late stage disease is well taken. But I have a question. The BMS drug + 7977 has a phenomenal SVR rate. But who was in that study? Were there Stage 4 patients involved? I don't honestly know. That makes a huge difference for those of us in the hardest to treat segment of the population. And what about previous null responders? Am I wrong or was the BMS/Gilead study just for treatment naive patients? Often drugs look much better in trial than they do in "real" life, especially when they are only given to patients with a really good profile.

I still don't think a petition is the best way to go abouth this. Letters to the pharma company work much better. On-line petitions are not very well thought of by any group whether it is government or the private sector. At change.org they often have a note saying that signers should follow up with a letter to their legislators or to the people they want to reach.

If you know my answer to who was enrolled in that study, I'd appreciate it. I was horrifically disappointed when 7977 + ribavirn that I was waiting for was canned due to such a dismal rate of failure in us cirrhotic patients while it did so well with treatment naive.

[UKgirl55]

Now that was the most well written post I've ever read. It has literally moved me to tears.

[FaithforHealing]

Just posting the link to the petition again to keep it at the forefront so everyone has a chance to see it and sign it.

Regardless of Gilead's real motives, good or bad, we need to keep the chatter alive....silence is deadly.

http://www.change.org/petitions/gilead-sciences-a-phase-iii-collaboration-for-the-treatment-of-hepatitis-c

[Willy50]

Thank you for the compliment. : )

I often read that 8-10,000 die annually from HCV.  
As this group of people die, other decompensating patients move to take their places.  
And so each year there is not a decent cure, a large number of people die.  The numbers aren't in quite yet, but this 10,000 per year mortality rate is a large percentage of the number who have treated this year since triple therapy has been approved.

I mentioned that it is still too early to know what Gilead will do, but in the race for getting drugs or drug combinations approved, it does not seem that Gilead is in any hurry to partner with Bristol Myers.  You have to wonder about the numbers of people who will be affected by this lack of cooperation.

Many of the people who will be affected are too liver compromised to be able to treat with SOC.  The odds of success for normal HCV infected patients are *better* with triple therapy, but that sad fact remains that the most cirrhotic are the least likely to be able to survive an even tougher and longer treatment.  Cirrhotics have increased mortality risk, a lower success rate and many of them are past treatment failures; non or null responders.

The dual acting antivirals, such as the ones partnered with Gilead and Bristol Myers Squib have a 100% SVR rate and a lower side effects profile.  This is a drug that seems to have the greatest chance of curing this group of 11th hour patients.  These people are not only in the 11th hour, but in the last 15 minutes of the hour.

I think that one can infer that if Gilead does not partner with BMS on the next step in getting the combination through FDA approval that for a certain number of these people the clock will run out.

If Gilead recruits from within with their own drug to partner with 7977, then I would guess that they would need to start with Phase 2a trials again, as they would with any new partnering.  I won't attempt to guess at the amount of delay that would involve, but a safe estimate would be a greater than 1 year delay.

When the drug company uses a "wait and see" answer about the potential partnership, I wonder if this is indeed a race.  
When they mention waiting to see results, I wonder if they don't already have the needed results.  In this age of SVR4's one knows a lot in just weeks after EOT, and I would wager that companies understand the viral kinetics of a compound or treatment in short weeks after commencing.  

I would venture that a trial could be started tomorrow, one with a 12, 16 and 24 week arm or if they had intended to partner; it would have been already set up, or some other trial configuration.  
I don't see plans, haven't read about any plans however...... other than waiting.  

As another sage member wrote; they have 11 billion reasons.....
This is not the type of response one would have expected from the leading HIV drug company.

This is just one guy's viewpoint.  I don't have all the facts, there isn't a lot of data, we don't know what Gilead will do, or Bristol, but to me it looks a lot like the mythical 100 MPG+ carburetor that have the rights bought up and was removed from the market.  
Here is a highly successful (don't come much better than 100%) drug partnership poised ready to enter further trials....phase 3?  Instead, the partnership sits on the side of the tracks like an empty railroad boxcar while people die.

I don't think Gilead would give much weight to my one signature on a petition, and so here I am today; venting and hoping that I am terribly wrong about all of this.

willy

[UKgirl55]

I was asked by this forum to respond and recognize which reply was the best answer to my original post. There are so many good answers and I want to thank everyone for responding. I continue to hope people will still post their views because we're not finished by a long shot!

I chose Willy50's comment posted on April 20th. In response to the possibility of Gilead not partnering with BMS for the cure;
His last sentence of, "How many lives lost, how many dollars earned?" said it all for me.

[rivll]

I hacked up this poor article to make it fit-please go to the original. Same link as the article by Adam Fuerstin.
The bottom line is that Gilead is still saying it has not refused to partner with BM-if that is true, a Facebook campaign may change it's mind. They will always be profit first, but their image means something to them. Maybe...

[rivll]

By Nathan Sadeghi-Nejad 04/23/12 - 06:00 AM EDT
Let me make one general observation about the future of hepatitis C treatment before I recap and grade each of the companies with a significant presence at the EASL meeting. Interferon -- the injectable immune system booster saddled with troublesome side effects -- is dead. The future of hepatitis C therapy belongs to interferon-free regimens. Physicians at the conference talked about interferon as if it were invented in medieval times.
An impressive 88% of treatment-naive patients in ELECTRON achieved sustained virologic response four weeks after stopping treatment (an early indication of "cure" known as SVR4) with 12 weeks of GS-7977 and ribavirin (RBV), a companion drug used in hepatitis C. Expectations leading into EASL were for an SVR4 of 70%.

Results from the ELECTRON AND QUANTUM studies of GS-7977 were important but not the star of EASL. What got everyone really excited were data from the mid-stage study combining GS-7977 with Bristol-Myer Squibb's(BMY_) NS5A replication complex inhibitor daclatasvir. Among the patients with genotype 1 hepatitis C, GS-7977 plus daclatasvir resulted in an SVR4 rate of 100%. Yes, the combination therapy cured all treated patients. These data literally elicited high fives from several of the generally reserved hedge fund analysts in attendance. It's hard to argue with an SVR4 of 100%, but longer-term follow-up data are needed to confirm these results. Physicians traditionally use SVR12 (12 weeks) or SVR24 (24 weeks) as a final indication of cure, although recent data show a strong correlation between SVR4 and later follow up assessments.
As if that weren't enough excitement, Gilead also generated some drama at the meeting -- and elicited a "patients-not-profits" rebuke from my colleague Adam Feuerstein -- when word got out that the company had refused an offer from Bristol-Myers to collaborate on further development of GS-7977 and daclatasvir.

[Willy50]

Consider this quote;
http://investors.vrtx.com/releasedetail.cfm?ReleaseID=665491

""More than 30,000 patients have been treated with INCIVEK in the United States and Canada in less than a year, making it the most prescribed direct-acting antiviral for chronic hepatitis C," said Christopher Wright, M.D., Ph.D., Vertex's Senior Vice President..."
-----------------------------------------------------------------

But Gilead wants to sit and wait to see results?  They have no plans made at the moment, no agreement at the moment.  If they were in a hurry to earn they could be in an even better position than Vertex is now.  

======================
http://www.thestreet.com/story/11503957/1/grading-hep-c-stocks-exiting-easl-confab.html

"Results from the ELECTRON AND QUANTUM studies of GS-7977 were important but not the star of EASL. What got everyone really excited were data from the mid-stage study combining GS-7977 with Bristol-Myer Squibb's(BMY_) NS5A replication complex inhibitor daclatasvir. Among the patients with genotype 1 hepatitis C, GS-7977 plus daclatasvir resulted in an SVR4 rate of 100%.  Yes, the combination therapy cured all treated patients."
============================

They have a winner and they are going to hold their compound and develop from within.  That means a delay in approval I believe.  I also believe that it is not yet known how effective the new GS compound is, or how safe.  (it could be more or less that the BMS compound).  Several compounds have been found unsafe in the last 6 months and it could happen again with any drug or combination of drugs.

Since these things don't happen in a vacuum, a non-partnership could spawn other non-Gilead collaborations.  The first pairing of 2 or 3 DDA's may bring a lot of revenue upon approval

willy

[Bill200]

They said they wanted to wait a few more months to see if their own compounds worked as effectively as the combo with BMS compounds.  The article was kind of slanted.  Of course if they can come up with their own 100% cure rate why should they collaborate with BMS?  

I guarantee you I want a cure as much as anybody on this board but I'm not gonna begrudge them yet, if more time passes perhaps another story then.

If you want something to complain about how about how long it takes drugs to get to normal people not in trials?  I think it should be more up to the doctor and patient whether to prescribe early or not.  Especially critical cases where time is of the essence and after it reaches a certain phase (II or III) with results.  The FDA is the main problem in my opinion.

[mdudley]

I just signed it!!!!  Yay!  Let's let the world know that there is a CURE and we want it, and we want it NOW!!!

[sheepdoggie]

A petition was begun to encourage Gilead to do the right thing.  Please sign it:
http://www.change.org/petitions/gilead-sciences-a-phase-iii-collaboration-for-the-treatment-of-hepatitis-c

[UKgirl55]

Excellent Willy!

This forum sometimes comes up on Google. This is one thread I'd like to see out there!

[katla]

This thread was such an interesting read and gives much to think about. I'm grateful to have this forum and I appreciate all you clever people who contributed. :-)

[libzo2]

Just a comment:  Perhaps Wallstreet has tainted the process which has filtered down to many of our individual doctors for example when I went to my expert doctor and saw that he had a new certificate on his wall, it was not for a new medical avenue; it was for business science from Georgetown U.  I wondered if I had changed from a patient under the doctors oathe or an asset to his black line in some account book.  Maybe Pharms should be forced to swear the Hippocratic Oathe as well (as if that would make a difference).

I feel like the waters are full of sharks.

[gonnabhepcfree]

My doctor told me on one of my visits that he see's an all oral regime with in the next five years and now they just have to figure out which combinations work the best with the least side effects. He also said he believes there will come a time where you will go to your primary Dr and get a prescription and won't need a specialist to treat.  Dr Hassanein was involved in the trials for interferon before riba.  I will be happy to see him on my next visit having reached SVR12 with the 7977 and bms combo.  He is in Barcelona but  I will find out anything I can on my next visit regarding the future of my combo.

[willbb]

Greed certainly is not always good . however unfortunately in big business(and there is not much bigger than Pharma) it will always be the main factor .

Best..
Will