Daclatatasvir & Sofosbuvir

Let's end the lack of cooperation between Gilead and Bistol Myers and get these two drugs on the maket to the people who need them.  The only way we can do that is through our White House Petition.  Pleas sign at www.hepc-cured.org we on have until 3/20/13 to get 100,000 signatures to have the white house intervene.  Please have your friends, relative, neighbors sign and add it to their face book and twitter... we need to end this deadly disease now. 4 million in US have this disease, 170 million world wide, hepc killmore people today than AIDS, a 1000 people a day die waiting for a cure.  Take action now---sign the petition.  Thank you

Return to Poll

16%

 (1) 

You signed the petition

83%

 (5) 

You signed the petition and are getting others to do so as well

6 Members voted

[Quest5245]

I am not sure how this site works but the drugs we need to cure hepatitis c is daclatasvir and sofosbuvir.

[hrsepwrguy]

http://www.medhelp.org/posts/Hepatitis-Social/Could-we-all-sign-this-petition-for-the-The-Whitehouse-to-get-Gilead-on-the-move/show/1908083

http://www.medhelp.org/posts/Hepatitis-Social/Sign-petition-to-put-pressure-on/show/1722631#post_8817062

http://www.medhelp.org/posts/Hepatitis-Social/Do-you-know-about-this/show/1904195

[can-do-man]

Maybe Medhelp can just start a forum for nothing but this, this is getting unreal folks.

[rivll]

I have always supported the petition but I am confused by a few things and I will not pass this new petition onto friends and family until these questions are answered.
Gilead is currently testing Sofosbuvir with their own GS5885. It looks promising. Bristol Myers also have some promising drugs in the works.
They are all working on this at a furious pace (yeah, maybe for profit, but so what? We still benefit).
It seems rather naive to expect that because Sofosbuvir and Daclatasvir are a cure for many, that we will expect Pharma to drop everything else and proceed with our drugs of choice even if a million people sign the petition.
If there was nothing else in the mix, I would be more supportive of this push, but Gilead and the others are working on it.
How do you suppose we could persuade them to switch gears, when 1. it may not be a cure for all and 2. They already may have a comparable drug
to Daclatasvir?

[Willy50]

I was an earlier supporter of the concept of promoting the continuation of the collaboration.  That made sense in March and April of 2012.

The goal in my mind was the most rapid passage of the most efficacious treatment.  My fear was that Gilead would not be able to rapidly move approval forward, and in the worst case scenario, the trials would have to be replicated or that the compound GS5885 would not be as powerful as Daclatasvir.

As it turned out, Gilead WAS able to fast rack the approval of a combination using 7997 & 5885.  Phase 3 trials with this combination started dosing in Oct or November 2012, and NDA approval is expected in 2014.  It wasn't a seamless transition, but I don't think one could argue there was much more than a 6 month delay.

In terms of efficacy, I have not seen any data which supports that one compound or the other, either GS 5885 or Daclatasvir works better with 7997 (sofosbuvir) better or worse; they seem to be equivalent.  I am unaware of any proof (yet presented) stating that Daclatasvir would be superior to 5885.

At present, there is probably more evidence which now exists that supports the safety and effectiveness of the two Gilead drugs in combination, than 7997 in combination with Daclatasvir.  If this is true, the finish line is closer with the 2 Gilead drugs in combination than with a Gilead/Bristol collaboration.
(please correct me if I am wrong)

I greatly admire the earnest attempts to move this forward, but each month that 7997 & 5885 moves closer to approval and each month that 7997 & Daclatasvir does, the compelling need for the collaboration diminishes. (IMHO)

It is another question entirely whether ......no matter how many signatures are collected...... whether you can force a collaboration between corporations, any more that you can enact legislation to force people to marry, no matter how good the intentions are or how good the outcome might be.

best,
willy

[Quest5245]

Gilead's sofosbuvir & 5885 are only achieving sucess with the use of ribavirin.  Ribavirin is just as toxic as interferon.  I don't know about you, but I do not want to take toxic drugs that and still do not cure the hep c and lead to "other" life long health problems because of using a toxic drug.  The only 24 week trial that attained 100% SVR without toxic drugs is when daclatasvir and sofosbuvir were combined.

I do not want to wait while a cure exists now.  Nor do I or want anyone else to continue to be used as laboratory animals while a drug company wants to put profits before patients.

Gilead refuses to cooperate with Bistol Myer so they can get the entire Hep c market, Gilead 5885 is having, at best, poor results  unless the RVB is added to the mix.

[Quest5245]

Willy,

Gilead is only having any sucess with sofosbuvir and 5885 if they combine it with ribavirin.  A toxic drug.  Nothing has attatined the 24 week, 100%, non toxic cure except daclatasvir when combined with sofosbuvir.  Gilead is trying real hard to bury that results.  If a trial only results in 60% to 80% SVR..........it isn't a cure!  Especially when they can only get that results if they use ribavirin in the mix, a toxic drug that has horrible side effects and leads to other life long health problems from its use.  

[dointime]

Both the Gilead 7977 and the BMS daclatasvir look good enough to get approval in other combos eventually.  So won't doctors then be able to cherry pick them and write their own off-label combo?  That is unless 7977 is only issued in the form of a combination pill.  

dointime

[Willy50]

First off, to dointime.  Since sofosbuvir has been in trials for treating geno 2's and 3's with ribavirin it will seek approval for the same and will likely be approved as such.  This means that the pill.....7977/sofosbuvir should be available by itself.  Once approved......daclatasvir should also be available in separate pill form.

It is another question whether a doctor would prescribe either off label, or whether insurance would pay.  I'm all for the safest, strongest treatment coming out sooner.  I'm just not aware of how companies can be "made" to collaborate and pay for trials against their corporate will.  The mechanics looks possible until prescribing and paying comes into the equation.

Next.... Quest......  Thank you for your reply.  There exists an issue; we don't have all the data. I believe that the data exists, but I do not believe either of us has a large enough number of responses (successes, failures, response rates when compared to staging,  genotype, geno subspecies and il-28 genetic marker to make broad claims. You *could* be right, but what trials, what numbers are you basing your claims on?

You are extrapolating success, but with very few numbers. (I think)

Back in Oct/Nov 2012 Vertex started ION-1 for naives. 200 people, 50 per cohort, 7977 & 5885 with and without Riba for 12 weeks, and the same with and without riba for 24 weeks.
The second part of that trial is about to commence.  Now that the 2 -12 week arms are done, and will very soon have their 4 week EOT PCR's we will have the results of a 12 week trial of 7977 & 5885, both with and without riba.  Presumably a SVR-4 will be highly predictive of success.
600 more trial particuipants will start in cohorts designed around the success of the first cohort design.  
In a matter of a few weeks we will see what Gilead is betting on.  If you are correct, you may see trial design of 12 weeks of 7977 + 5885 + Riba. (or if it is a real failure it may be 24 week duration) If you see them drop riba and go with 12 weeks of treatment we may infer that you are incorrect; that they CAN treat people for 12 weeks without riba.

You can also note that Gilead is doing a trial (lonestar)....has added a trial..... a small one in which small groups will treat w/ 7977 & 5885 for 8 weeks.  I think it will be about 25 per arm, in this case about 25 people on 7977/5885/RBV and the same size group w/ the 2 compounds but NO RBV.  I infer from this that they have indeed had success treating without the combination of the two drugs without riba.  I mean.....if they had failure w. the 2 drugs without riba in 24 and 12 week......why would they try a trial for 8 weeks?  I do not claim to know or possess the facts.  Which trials are you suggesting prove that they need RBV to treat successfully?
I am inferring they have had success.

I have an open mind about this, but I admit being cynical that someone can force the drug companies to collaborate.

On that note...... have you noticed that Vertex has a new shared compound als2200?  It's pretty similar to 7977.  7 day monotherapy, 4.5 log drop mean in 5 days and 4/8 were below level of quantification.  This would be an excellent possible collaboration w/ Bristol..... Vertex had the shared rights to it and have shopped it around, but for whatever reason it appeared that Bristol is not collaborating. I believe they have worked out an agreement w/ 1 or 2 other companies, but not Bristol.

Check this out;
http://www.natap.org/2012/EASL/EASL_24.htm

I don't claim to know the answers, but until I am shown more data I am of a mind that I cannot influence these companies and I am not certain that what they are pursuing is inherently worse that the 7977 and Daclatasvir collaboration.

And yes..... in a better & more perfect world they might have continued the collaboration.  When they paid 11 billion for the compound (7997) it almost made a collaboration impossible.  : (

willy

[Willy50]

5th paragraph starts out;
"
Back in Oct/Nov 2012 Vertex started ION-1 for naives."

should read Gilead instead of Vertex
==========
also
http://www.gilead.com/pr_1771657

[can-do-man]

Looks like you are right dointime.

In addition, he said, both daclatasvir and sofosbuvir are likely to be approved soon, with an indication for therapy in combination with the standard HCV drugs, pegylated interferon and ribavirin.

There would then be nothing to stop doctors from using them together off-label, while avoiding the other two, which are associated with a host of adverse effects.

http://hepatitiscnewdrugs.blogspot.ca/2012/11/daclatasvir-and-sofosbuvir-promising.html

[Quest5245]

Once Gilead combines it sofosbuvir with its 5885 the doctors can not, as you mention, using them (sofosbuvir and daclatasvir) together off-label.  You will not have that right.  You will have to use Gilead's combo and doctors will not be allowed to give you Gilead's combo and daclatasiv.  They only reached the non toxic successful cure rate with only two drugs....sofosbuvir and daclatasvir.  As to date Gilead has not attented the success it did when these two drugs were combined.  We keep repeatig the same thing over and over..

[hrsepwrguy]

"In addition, he said, both daclatasvir and sofosbuvir are likely to be approved soon, with an indication for therapy in combination with the standard HCV drugs, pegylated interferon and ribavirin"

Meaning the compounds in question will be available in stand alone form
----------------------------------------------------------------------------------------

"There would then be nothing to stop doctors from using them together off-label, while avoiding the other two"

Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration.[1] In the United States, the Food and Drug Administration Center for Drug Evaluation and Research (CDER) reviews a company's New Drug Application (NDA) for data from clinical trials to see if the results support the drug for a specific use or indication.[2] If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route of administration, and other information to be included on the drug's label. More detail is included in the drug's package insert.

The FDA approves a drug for prescription use, and continues to regulate the pharmaceutical industry's promotional practices for that drug through the work of the Office of Prescription Drug Promotion (OPDP, formerly the Division for Drug Marketing, Advertisement and Communication (DDMAC).[3] The FDA does not have the legal authority to regulate the practice of the medicine, and the physician may prescribe a drug off-label. Contrary to popular notion, it is legal in the United States and in many other countries to use drugs off-label, including controlled substances such as opiates. Actiq, for example, is commonly prescribed off-label even though it is a Schedule II controlled substance. While it would be legal for a physician to independently decide to prescribe a drug such as Actiq off-label, it is illegal for the company to promote off-label uses to prescribers. In fact, Cephalon, the maker of Actiq, was fined for illegal promotion of the drug in September 2008.[4] Under the Food, Drug, and Cosmetic Act (FDAC) at U.S.C. 21 §§301-97, manufacturers are prohibited from directly marketing a drug for a use other than the FDA approved indication. The Food and Drug Administration Modernization Act of 1997 created an exception to the prohibition of off-label marketing. Manufacturers are now able to provide medical practitioners with publications on off-label uses of a drug, in response to an unsolicited request.[5] In 2004, the federal government and whistleblower David Franklin reached a $430 million settlement in Franklin v. Parke-Davis to resolve claims that Warner-Lambert engaged in off-label promotion of Neurontin in violation of the Federal Food, Drug, and Cosmetic Act (FDCA) and the False Claims Act. At the time, the settlement was one of the largest recoveries against a pharmaceutical company in U.S. history, and the first off-label promotion settlement in U.S. history.[6]

http://en.wikipedia.org/wiki/Off-label_use

[can-do-man]

Quest you come here, slam members and mislead, I left the link that was in so please read. BTW that came from a well known Doctor not myself saying it. Unlike what you just posted to me.... Please take the time and research

[dointime]

"It is another question whether a doctor would prescribe either off label, or whether insurance would pay."

Willy50 - Yes, valid points.  I think we shall have to wait and see how the Gilead combo pill matches up to the combo with BMS.  If Gilead falls short then I think many doctors would be willing to get creative with their prescriptions.  Insurance companies might be stickier but just imagine the outcry if people were dying while the cure was already sitting on the shelves.  If the Gilead combo is that much worse then Gilead may even have to eat humble pie and go back to BMS with cap in hand.  Many outcomes are still possible, unfortunately taking even more time which many of us don't have.

I agree that we haven't got enough results yet to really know whether and in what circumstances ribavirin will be required with the Gilead combo pill.    

Hiya can-do-man and thanks for the link.  I am pleased to find out that there are others out there formulating a Plan B if Gilead drops the ball.  

dointime        

[Willy50]

I do not think that it is a shoo in that all doctors would simply write scripts off label.  I have seen some people who wanted low dose naltrexone, an approved drug, but they wanted it formulated so that they were taking something like 1/10th of a dose; no dice.

Here is a drug (naltrexone) that has been approved for many years, is safe and has no danger for abuse, but people still can't get doctors to write a script.

The summer that Incivek got approved many people got turned down by insurance companies..... for an approved drug.  There were a number of threads on this and people were just advised to insist, to put it in writing, to have the doctors call the companies, etc.  Insurance companies did not want to spend the extra $$$.  I think you can infer what many would say about coughing up and paying for not 1, but 2 premium priced drugs that are not FDA approved together.  
They will say; "NO".

So....to make it work, most of us need both; a willing doctor and a willing insurance company.  If you are lacking one you are probably out of luck.

I might venture a guess that the drug pricing could be such that the 7997 & 5885 combo might be "X price, and the single price of 7977 could be 5/8 or 3/4 price.  This would mean that if you had to order ala carte off of the menu buying 7997 and daclatasvir could end up costing you more money than the 7997&5885 combo; yet one more disincentive.

If you think that a company that spent over 11 billion for the drug before they spent a dime on trials is going to make it easy for Joe 6 pack to outwit them you may be in for a rude awakening when you try to outfox them.  

The trials at far from finished.  I hardly think it is safe to assert that 7997 and Daclatasvir are proven, or safe..... not in the numbers of results we have seen.  Nor is it safe to assume that 5885 and 7997 are any of the above; safe, efficacious or are guaranteed for approval.  Either drug combo could fail in some unforeseen way 5 foot before the finish line.  I don't expect it but  look at Incivek and Victrellis; they both have black box warnings now they didn't have when they were approved.  Look what happened to Bristol's 7997 replacement drug from Inhibitex;

http://www.pharmalot.com/2013/01/bristol-myers-tries-to-settle-hep-c-patient-claims/

I know that some of the info in these threads isn't super accurate, but the intentions are good and in a sense all they are asking for is some sort of consideration for using the 2 "best in class" drugs in combo.  If for some reason the drugs currently in trials were to fail I would imagine that any of us would welcome a back up plan.  I don't see how it could would work, but what if it was some sort of approval to use them off label, which as it sits now..... I find hard to envision it happening.

However........I remain dubious that the owners of the drugs will be swayed, or that government will intercede.

willy

[Willy50]

My above post was only partially directed to DT, but really it was mostly directed to "all" in the forum.

[rivll]

Really good posts Willy and doin time/

[Quest5245]

Murphy: Hepatitis and the pharmacology of greed
Posted: February 25, 2013 - 10:35pm  |  Updated: February 26, 2013 - 12:06am

  Advertisement

By Mark E. Murphy
Murphy: Hepatitis and the pharmacology of greed
Savannah Now
Mark E. Murphy
February 26, 2013 12:06 AM EST
Copyright 2013 Savannah Now. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
I was eight years old, making rounds at the hospital with my father, when I first met the Yellow Man.

His eyes were an astonishing saffron color. His skin was also striking — an iridescent bilious hue.

My father sat poring over the Yellow Man’s voluminous chart in the nurses’ station, reading glasses perched on the end of his nose, while I tried my best to stay quiet.

Ultimately, I couldn’t.

“Why is he that color?” I asked my dad in a whisper.

“He has hepatitis,” my father said matter-of-factly, never looking up.

I nodded. I was fascinated. I even talked to my third-grade class about the Yellow Man later that week in Show and Tell. But I had no clue what my father was talking about when he told me that the Yellow Man had “hepatitis.”

Today, I do.

You see, I am a gastroenterologist. In my medical specialty, we deal with Yellow Men (and Yellow Women) just about every day. And many of them have various forms of hepatitis, or inflammation of the liver.

Some get it from alcohol; some, from medication. But an emerging variable in the growing liver disease population is hepatitis C — a viral illness that is now the leading cause for liver transplants in this country.

Over 170 million people worldwide have hepatitis C. More than 4 million of those people are in the United States. A lot of those folks acquired hepatitis C through blood transfusions (there was no blood test for the virus before 1989); some got it through IV drug use, or through tattoos and body piercings. A shocking 30 percent have no risk factors for it, and have no idea how they became infected.

So why is hepatitis C a problem?

Because it is a stealth epidemic.

You see, most people with this disease are not “yellow.” In fact, most of them have no symptoms at all. None, that is, until they develop cirrhosis and liver failure — or worse still, liver cancer. Hepatitis C is now the leading cause of liver cancer in the United States, and is the most rapidly increasing cause of cancer death in this country.

Hepatitis C kills more people every year than AIDS.

Let that sink in for a moment.

Traditionally, hepatitis C has been treated with a combination of an injectable drug called interferon and another orally-administered medicine called ribavirin. It’s a grueling regimen, resulting in nausea, malaise, weight loss, skin and hair changes, anemia, thyroid problems and depression in many patients.

Moreover, the cure rate (technically called “sustained virologic response,” or SVR) for this regimen is less than 40 percent after 48 weeks of treatment. Many people cannot complete the full course of therapy because of the horrendous side effects.

Now, to the punchline.

At a recent national medical meeting of liver specialists, Dr. Mark Sulkowski of Johns Hopkins University Medical Center described a Phase II research protocol using a combination of two new oral medications, daclatasvir and sofosbuvir. This medication combination has almost no side effects.

The gist of Dr. Sulkowski’s presentation is this: After a mere 12 weeks of treatment with this new regimen, the “cure” (SVR) rate for hepatitis C was an astonishing 93 percent.

When I read this, I literally stood up and whooped.

Hepatitis C patients have been waiting for a treatment regimen like daclatasvir and sofosbuvir for decades. It’s a true rarity in medicine — an honest-to-goodness game-changer, a phenomenally effective regimen for a serious, life-threatening disease that is also safe and well-tolerated.

The only problem? The two drugs are owned by different companies — daclatasvir is a Bristol-Myers-Squibb drug, while sofosbuvir is made by Gilead Sciences.

For reasons that are almost certainly financial in nature, Gilead has refused to do further work on this drug combination with Bristol-Myers Squibb, so there will be no further study of the regimen. With no Phase III trials, that means that the daclatasvir/sofosbuvir combination regimen will likely not be approved for use by the FDA.

Gilead has issued no formal commentary about why it does not wish to pursue further development of the new regimen, although there is speculation that it is altering its focus to produce single-tablet combination regimens — a product line that has been highly successful for the company in the treatment of HIV.

In fact, Gilead is doing quite well financially. It is a company with over $4 billion in annual revenues and over 4,000 employees. Its average margin of profitability over the last five years has been a whopping 34 percent.

Moreover, the total return to its shareholders on Gilead’s stock has been nearly 95 percent over the past year.

Still, the salient question is this: Should Gilead Sciences’ profitability trump doing what is right?

Since Dr. Sulkowski’s data presentation at the AASLD meeting in Boston this past November, over 200,000 hepatitis C patients worldwide have died of complications of their disease. Meanwhile, Gilead, a tremendously profitable corporation, refuses to consider the development of a drug regimen that could have cured most of those individuals in the pursuit of even greater profits.

I find that unconscionable. In fact, I find it patently offensive.

In short, it’s just plain wrong.


Mark Murphy, M.D., is a Savannah physician and writer. ***@****




Comment

[Quest5245]

You stop misleading the people here.  I am not like you that have nothing else to do in their life except write lengthy, meaningless, nonsense.   Gilead combines sofosbuvir with 5885 and that is what they plan to do,.Gilead has no intention of just manuf. sofosbuvir by itself.  (where did you ever come up with that one) Gilead intends to make a combo pill of sofosbuvir and 5885 and  use ribavirn (a highly toxic durg) to treat Hep C people.  Bristol Myers will have no choice but to combine its daclatasvir with another drug and hopefully the will not require ribavirin to get any success Gilead must use ribavirin with there combo to get success..  Doctors will not be able to say ok, I will prescrib you sofosbuvir and daclatasvir because they will not be separate drugs(where ever did you get that from)....they will be combo pills.  Get it yet?  When sofosbuvir and daclatasvir were combined in the 24 weeks patients had SVR and no relapses to date in Hep C 1a.  We have many doctors backing us including Dr Mark Murphy. Who article I published before this post.  If it did not post then I would be glad to send it to your email for your review if you dare provide it.  The only two drugs together that cure without the use of toxic drugs is sofosburvir and daclatasvir.  If you still don't have it, the White House Petition   www.hepc-cured.org   Gilead is strickly putting profits before patients!

[rivll]

You make it sound like those 200,000 HCV patients worldwide would have been saved...when you know well had GS and BM cooperated and developed the drugs together those patients still wouldn't have had access.

The petition is fine, I signed it, but you need to be realistic. We are all disappointed that they will not work together but this is just beating one's head against the wall. There are other combinations in the works and even so, daclatasvir and sofosbuvir may end up available separately.
I do not disagree with you but I disagree with the frantic spin of your manner of persuasion.

[rivll]

I just read your 2nd post...unbelievable.
You just shot yourself in the foot.

[Quest5245]

Rivll,  Unless we get the cure here the rest of world doesn't stand a chance.  Yes there maybe "other things in pipeline" but why should be continue to used as laboratory animals when we have found a cure.  I have to say,  that when people decide to pick on a word  or two that may sound rash or out of sorts  to them or not acceptable to them......that is not the point here!.  We are dying from Hepatitis C, we are being given toxic drugs over and over again with horrible side effects, , people are dying every day waiting for a cure..  It would be nice if we all could see past our "hen picking"!  

[Willy50]

In answer to your question; how do you suppose that Gilead is going to treat genotype 2 and 3 patients when (as you maintain) they will only provide co-formulated 7977/5885 compounds in a single pill?

Answer; they are treating, currently in fda trial approval to treat g-2 and 3 with 7997/sofosbuvir and riba.  If you knew your subject you would know that.  They will not co-formulate it (w/5885) to treat genotypes 2 and 3.

Good luck with the endeavor.  

Willy

[can-do-man]

Well I have to say I found Willy's explanation in the post you attacked as one of the better posts I have read about this. I noticed once again you use the term "we" and "us" and it has become quite clear who "we" are. To be brought here just to mislead and attack is not helping the cause. There is more knowledge about Hep C on this forum then both of you have combined...... Go play elsewhere as there are forums out there that you can get by with your nonsense.

[dointime]

Looks like we got ourselves another wise ***.  Ho hum.  Just when I was managing to forget the last one, somethinglady, wasn't it?  Is there a factory somewhere churning these guys out?  

dointime

  

[purplecat]

Do you have hepatitis C or just lobbying for petition?

[dointime]

"all they are asking for is some sort of consideration for using the 2 "best in class" drugs in combo."

As I remember, Willing was calling for this years ago and was equally dubious that it would ever happen.  Her take on it seems prescient now.  

As you say, there's many a slip twixt cup and lip.  It's surprising really that anybody ever gets their ducks all lined up in a row.  Good luck with yours.  Mine have still to hatch apparently, never mind line up.

dointime

[Willy50]

Speaking of collaboration......Gilead is still in a few. This one cured everyone they treated  This one is Sofosbuvir and Simeprevir (TMC435, a PI, very similar to Incivek or Victrelis, but a cleaner side effect profile)

http://www.bloomberg.com/news/2013-03-04/gilead-medivir-hepatitis-c-drug-clears-virus-in-patients.html?cmpid=yhoo
========
also a more technical write up is on Natap but you have to go there to find the article.  There is a chart, but the bottom line is that in every category which they treated they cured.  To be fair, I believe they were all null responders, but with minimal staging damage F-0 to F-2
========
From another natap article;

" Simeprevir is being investigated in combination with PegIFN/RBV in phase III trials and is also being evaluated with Direct-acting Antiviral (DAA) agents in four other phase II interferon-free combinations both with and without ribavirin (RBV)."

===========================
one of the Simeprevir trials is with Vertex's VX-135, a compound very similar to Gilead's sofosbuvir.

http://www.news-medical.net/news/20121102/Janssen-Vertex-to-evaluate-TMC435-and-VX-135-in-Phase-2-HCV-study.aspx

=============================
My point is that there are many many drug treatments being developed which will work.   There are actually more drugs in development.  This is one reason why the stockholders were so critical of Gilead's high priced buy of 7997 for 11 billion, and it is part of the reason they may have felt they could not afford to share in the profits with Bristol.

Note that many most of these trial will also have trial arms both with and without riba.  When they cure everyone such as in the first trial I referenced you can kind of imagine that they probably don't need the riba.

I rather think they will find that adding a third DAA compound might be cleaner, quicker and higher efficacy than using riba.  

willy

[rivll]

Thanks for that, it is very encouraging.

[can-do-man]

You brought up willing, what a huge loss to this place when he left. By far one of the best this site ever had........ I sure hope in his last treatment he made it to SVR...

[Fmulder]

No one cares about Hepatitis C! It's still a drug addict disease as far as the public is concerned!, I'm tired of waiting, I'll take my chances!

[dointime]

Great info Willy, thanks.

As you suggest, TMC435 is an NS3 protease inhibitor similar to Incivek or Victrelis.  This brings up again the thorny question of resistance for people like me who have already failed tx with a protease inhibitor.  There may be an assortment of drugs in development but resistance is still the same old minefield.  Lately this topic seems to have been placed on the back burner because 7977 apparently has such a high barrier to resistance that it is not an issue with 7977 (the jury is still out in my opinion).  That is not so for any other drug currently in development, at least to my knowledge.

So for my next tx selection, ideally I will be trying to avoid a protease inhibitor.  Also, if I am having an NS5A inhibitor like the BMS drug then I'll want to see a planB that doesn't include one of those either.
  
Until the cure rate is 100%, nobody can afford to run out of options because they are resistant to all available tx.  That is the name of the game we've got here.  At least that's how I see it.

dointime    

[child24angel]

I haven't heard of these two drugs, not that I remember .

I too hope willing is SVR, the last time he was here he was
treating. Yes, he was a huge asset to this forum. I hope
he will pop in some time and let us know.

[Willy50]

Here is a new trial I have not seen before listed

http://www.clinicaltrials.gov/ct2/show/NCT01805882?term=NCT+01805882&rank=1
NCT01805882

You'll note there are just two cohorts

Arms Assigned Interventions
Experimental: GS-7977/GS-5885 in treatment naive patients
GS-7977/GS-5885 for 12 weeks
Drug: Fixed Dose GS-7977/GS-5885
---------------------------------------
Experimental: GS-7977 + GS-9669 in treatment naive patients
GS-7977 + GS-9669 for 12 weeks
Drug: GS-7977 + GS-9669
-----------------------------------------

You'll note that both trial arms are 12 weeks.  You'll note that there is no ribavirin in either arm.

I am inferring that ribavirin is possibly not needed to provide SVR's, as was asserted by Quest in this thread (the originating poster).  I am assuming that this is based upon the ION 1 trials which commenced in Oct/Nov
2012.

willy

[George1813]

"Speaking of collaboration......Gilead is still in a few. This one cured everyone they treated  This one is Sofosbuvir and Simeprevir "

Gilead will not collaborate - not enough profit for them.

This trial was started when Pharmasett still owned Sofosbuvir (then PSI-7977)

Don't hold your breath for any further development of Sofos+Simeprevir,
even though both drugs are very advanced in testing any the combination could have been approved very quickly, and the results are excellent.

Just like Daclatasvir+Sofos, it will never see the light of day.

And the approval delay before a decent treatment arrives could well mean the death and suffering of thousands of us, unfortunately.

Other drug companies often collaborate on drug treatments,
and BMS is willing to work with Gilead.

Gilead overwelming motive is profit, not patient welfare,
which is not acceptable for a large pharmaceutical.

Anyway I have a feeling that what goes around, comes around and Gilead will get their just deserts eventually.

[Willy50]

I well, I doubt they will collaborate as well..... unless there was something they determined to make it more attractive.  Or a hurdle pops up somewhere.  I think the trial I listed in my last post was just one more way of hedging their bets, spreading risk and I believe seeing what sort of compounds work with 7997.  It was first posted at CT march 5; brand new,

Part of it was just pointing out; if you are going to force a collaboration; which collaboration?
If it were purely based upon efficacy, shouldn't one be interested in the efficacy of 7997 & 5885?
If the driver is the earliest to approval..... then it would now appear that the 7997 & 5885 combo is closest to that finish line.

Quest is taking some liberties with facts.  The 7977 daclatasvir combo isn't the ONLY combo which can cure.  It isn't the ONLY one that can cure w/o Riba.  It just isn't the only hope, and it probably is no longer the shortest distance to a cure.

I am not going to take Gilead to task (well, I have already, but not now) over the motive to make a profit, since all the competitors are exactly the same.  If you read up on any of these companies that is very clear.  It doesn't mean they are heartless (cause I do not believe that), but they do exist to make profit and advance their company.  
There have been a number of threads on the very topic, particularly back around EASL 2012.

That doesn't not mean I supported this initially; I didn't.  The fastest path to approval *had* been 7997 & Daclatasvir.  
Things change.  : I

willy

[purplecat]

I'm in current trial with 7977/5885 or what I call 7985 because of what is stamped on the pill. I started with 19,700,000 VL Week 2 UND.  Week 4 UND ALT 19 and AST 19.  Side effects Headache and some GI problems.Seems the pill causes excess gas that causes stomach pain and nausea.  I'm trying to control that with diet and doing much better. Alot of my favorite foods l can't eat right now, but small price to pay. I think others will have this problem.  Will the Nausea be too great that they have to stop treatment?  Headache too much to continue? Now that a bigger number of people are in these current trials I think this will be the case for a small precentage.  Like all drugs they have some side effects.  Nothing like INF/RIBA , I ran 6 miles last Sunday, I could hardly carry my dog upstairs to bed during SOC treatment.  My numbers are pretty amazing  with this 7985 combo, we shall see Very soon.    

[rivll]

"If it were purely based upon efficacy, shouldn't one be interested in the efficacy of 7997 & 5885? "

"The 7977 daclatasvir combo isn't the ONLY combo which can cure.  It isn't the ONLY one that can cure w/o Riba.  It just isn't the only hope, and it probably is no longer the shortest distance to a cure."

Good point!

[George1813]

Hi Willy
I agree with what you say.
7977+Daclatasvir is probably no longer the shortest path to approval.
If only phase 3 testing was started immediately after EASL, they would be close to filing for approval now, because both were already so advanced in testing,
and it may have been the best treatment ever developed, able to cure almost everybody.
But we will never know now.
It certainly deserved further development.
They could have been trialing 7977+Daclat with seriously ill, like pre transplants, instead of 7977+Ribavirin, which I am certain is less efficacious and more sx.

Anyway I don't think it hurts to support Magaret Dudley and the petition though.
She is just trying to get the best deal for all of us, by sacrificing her time, effort and probably funds.
I am pro private enterprise and the free market and creating profit and serving share holders.
But there needs to be some rules and regulations,
for instance a company can't just dump pollution into a river, because it is the cheapest thing,
especially if someone takes the trouble to complain.
And the regulations guiding big pharma are quite strict, to protect patient welfare.
Not saying Gilead broke any laws.
It just seems to me so wrong, what they did in this particular instance.
Sure, if they actually developed GS 7977, then they can do what they like, in my opinion.
But they purchased after it has shown excellent results in combination.
(and Pharmasett began development of it at a tax payer funded university - go figure)
Then they lock it up with their own drug, 5885 which causes a approval delay of at least a year.
And to me 5885 is clearly inferior to Daclatasvir in some ways.
ie. it will not work in GT2&3.
Which is probably why Gilead are testing other combinations, like in the new trial you mentioned.
And Gilead have talked about the new drug GS5816 + 7977, which may be more pan genotypic combo., but will still take years before approval.
Having said that, I personally would be ecstatic to get on the 7977+5885 combination, but its just not available here.
And I will probably just have to take my chances with Boceprevir triple tx,
and hope I am one of the lucky ones that survive intact.

[Willy50]

I think we look at this from similar angles but we may not agree 100%.  

Initially, I went on and on about Gilead and their decision.  At a certain point you have to accept; *this is what's happening now*.  

I'm not sure that they have any heavy Karma issues to deal with.  If anything, they are responsible for many HIV positive people surviving for decades.  Even that though..... is not the result of having pure hearts...... they do it as a for profit business.  IMHO, you can have profit incentive and good intentions.

Fact is, they just ran a very small trial, probably cherry picked the applicants (as can happen in trials).  Whatever they did the outcome is just too small to use as proof; this was the ideal.  It may have been, it might not have been.  We didn't run 1000+ people through so we really don't know.  I occasionally mention my father who was an early vioxx patient.  There was a drug that went all the way through trials and was on the market for..... maybe 5 years and was responsible for.....maybe 1/2 a million deaths.  My father died about midpoint through before they recalled it.  So figure 5 years trials and 5 years of use= 10 years and the drug got recalled.  

Point is..... you need many trials, many groups, large numbers to be able to really make statements and be fairly sure you are correct. Even then, ya ain't.

I love the idea of combining best of class. So..... how does one do that?

I don't know how to reinvent our system. I agree it is flawed.  In spite of this the United states has a pretty large pool of companies working on curing HCV.  HCV is a virus that has had a cure for over a decade.  Most viruses we have not been able to cure, but the medical community had done a good job with our disease.

I have to wonder if you are correct about calling it a year delay.  The discussions about the end of the collaboration happened right at EASL; mid april, 2012.  Add 6 months to that, lets call that a delay; mid may is 1 month, june-2, july-3, august 4,september-5, mid October would be 6 months.  The first naive trials for 7997 & 5885 started in october, almost exactly 6 months.  If you check boards I think you'll find some may have even treated earlier, but I got my call in october 2012.  The naives trials were filled by about 1/3d week in October.  I know cause I missed out by one slot.

One might even argue that lives were saved because Gilead bought this compound and had the money and know how to push it through trials.

Look at Vertex and their second phase trials of quad therapy or their polymerase inhibitor. That second phase trial started several years ago, I think and has yet to start phase 3.  

(answer; NCT01080222  Telaprevir, vx-222, IFN and rbv
First received: March 1, 2010)    3 years- has not started phase 3 yet.)

Vertex started w/ telaprevir long before boceprevir, but...... do you remember which got approved first? : )

My point is that Gilead has done a reasonable job at moving these trials through the approval process.  They have possibly done a superior job.

Do we need pan-genotypic cures or specific compounds that get approved sooner?  In the United States we most need a cures for genotype 1's and null responders and a treatment that cirrhotics can tolerate safely.  I believe that there will be several treatments for g-2s and 3's.

The issue w/sofosbuvir and riba for g-2's is that in not adding one more new compound the TX gets approved 1+ year earlier.  It was about getting it to market.

The drive to beat competitors is one thing that caused these treatments to come to market quickly.  : I  
I'm just saying.... it isn't all bad.

willy

[George1813]

Hi Willy, I agree with what you said
I have pretty much resolved to move on from the GS7977+Daclatasvir issue, for a while now.
Not much we can do about it.
Just like to have a bit of a whinge occasionally, and wonder what may have been, if one company owned both drugs.
I agree too that Gilead is a good company to move the approval process through relatively quickly.
Sorry you missed out on the 7977+5885 trial by one place.
How about the second group of 600 starting soon, did you get into that ?

George

[Willy50]

(George wrote;)
Sorry you missed out on the 7977+5885 trial by one place.
How about the second group of 600 starting soon, did you get into that ?
===================================
I think they are just winding up the first leg of it and assessing SVR-4 PCR's.
If that trial started Nov 1(maybe not every single person dosed by Nov 1), 12 weeks of TX would be Nov, Dec, Jan.  4 weeks of Feb for a PCR and the results should be in about NOW.  I believe you will be seeing second leg trial participants on the boards withing a week or two, but we will see.  They should have the results now and they have had the response rates/viral kinetics (not SVR-4 cure rates) for a long time now.

This is a good place to mention as I did earlier, that if the contention that 5885 is inferior to Daclatasvir, this will be one bit of evidence to support or disprove the contention (although, it is never 100% clear since the mix of trial participants can also skew results)
==============

I have wondered if there could be a sort of medical bill (such as there are for "orphan drugs") which could serve to create an incentive for companies to consider such collaborations.  I'm sorry, but they are in it for the money, so how could this help drive their decision making to increase considerations such as Margaret is proposing?

A few ideas I had might be some sort of government co-pay for trials if the two drugs meet "best in class" designation, It could afford some type of expedited approval by the FDA, some tax considerations, maybe even an extension of the period before the drug would roll over to generics.  

If you put together a package like this.....perhaps Gilead or BMS might have continued the collaboration.  Obviously, their competitors might say this could give incentive to bid up the price of first in class drugs, something which already happened here.  It could tend to get these best in class drugs to approval sooner and potentially deliver the best combination sooner instead of second or third best couplings.  (likewise, it could just be one more government programs which could be "gamed". )

Just a random idea.

willy

[George1813]

I'm guessing 5885+7977 will be entirely adequate for GT1.
And a huge improvement on IFN based tx.
I've been hearing from several people on the ION trials, and they all seem to be UD by week 2 or 3, with reasonably mild sx.
And we have the 100% results of the Electron trial arm.
For GT2&3 7977+Riba is not the greatest, but still a huge improvement, and at least it will be launched soon.

You have some good ideas on encouraging collaboration.
I think BMS were willing to work with Gilead.
But maybe that was because they thought the best NS5B nuc (7977) was more valuable than the best NS5a non nuc (Daclatasvir).
Gilead do seem to be more profit driven than some other pharmas.
And really it is a question of degree.
All drug companies are profit driven to some extent, and rightly so,
but maybe some possibly to the exclusion of too many other considerations.
The HIV community is protesting vocally about the exorbitant prices of some of their AIDS drugs, compared to other companies.
Don't really know much about that issue though.

Anyway I just wish we could encourage the FDA to speed up the approval process.
8 to 12 months seems such a long time, from initial filing and all the trial results being in.
I would have thought that a committee working full could review that data in a month or two, at most.
Especially if there are no major adverse events in the trials, and the SVR rate is high.
Its just that there is such a huge need for these new drugs.

[alico222]

Hi,
I'm in uk... Geno 3....
Anyone any idea when Europe may approve sofosbuvir and rbv for us??
Also Britain did named patients thing for telaprevir before it was properly out... Does this happen in usa and might it happen for sofosbuvir in uk?

Can we ever get direct info from gilead?? Would they communicate at all with us to let us know of trials a d named patient intentions etc.. Anyone know!
Cheers...
Read all above posts with interest.. We at every much in the hands of the drug companies!,,
Ali X

[rivll]

Hi,
This is the latest. :)

http://www.gilead.com/pr_1804362
Gilead plans to file for regulatory approval of sofosbuvir in other geographies, including the European Union, in the second quarter of 2013. The European Medicines Agency (EMA) has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Accelerated assessment could shorten the EMA’s review time of sofosbuvir by two months. Granting of accelerated assessment does not guarantee a positive opinion from the CHMP or approval by the European Commission.