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"Is there no balm in Gilead? Is there no physician there?" Jeremiah 8:22
March 17, 2013 4:38 AM   Subscribe

Hepatitis C has possibly been cured, but... In April, 2012 a human study with a combination of Gillead Sciences' Sofosbuvir, and Bristol-Myers' Daclatasvir led to a 100 percent cure rate for hepatitis-C, the world's leading cause of liver disease. Unfortunately, Gillead, which paid billions for Pharmasset, the company that developed Sofosbuvir, refused to allow additional studies with Bristol-Myers, choosing instead to try developing a proprietary cure, possibly using highly toxic Ribavirin. They are also backing away from a similarly successful study completed this year, previously approved by Pharmasset. Since Gilliad's delay of additional human studies, approximately 300,000 people worldwide have died from liver disease related to Hepatitis-C and 40% of all available liver transplants have been diverted to a treatable disease, while up to 200 million additional infected people worldwide -- many of whom do not know they are infected until the end stages of the disease -- are still waiting for a cure. Meanwhile, Hepatitis-C activists are trying to petition the White House to find a way to resolve the impasse.

Hepatitis C is transmitted through blood and any activity that can lead to blood exposure. Many were potentially exposed to it through dialysis, blood transfusions, or organ transplants, which didn't screen the disease until the early '90s, and roughly one case in ten has no obvious cause, but could've been transmitted from things as benign as piercings and tattoos, acupuncture, or sharing nail clippers, razors, or tooth brushes.

It has infected approximately 1 in every 50 Baby Boomers, most of whom do not know of their infection until being tested for other potential liver problems. 3.2 million Americans are estimated to have it, and most cases remain undiagnosed until the disease has progressed towards its end stage. Those infected often do not develop symptoms for up to 20 years and can spread it to others without realizing.

Hepatitis-C now kills more Americans than HIV and known cases are emerging rapidly throughout even industrialized countries like the U.S.

Although often undiagnosed, it is estimated that Hepatitis C is responsible for approximately 40% of the 849,000 deaths worldwide from liver disease per year, or roughly 340,000 people. It also is responsible for about 40% of liver transplants, which could be used to save the lives of many thousands of others if if hepatitis-C is eradicated.
posted by markkraft (31 comments total) 27 users marked this as a favorite

 
(Dear admins: Oops! Failed to note the mistake on the next-to-last paragraph of additional info on Hep-C. It might be best to correct it to "Hepatitis-C now kills more Americans than HIV, and known cases are emerging rapidly throughout even industrialized countries like the U.S.)

In truth, the rate of infection has decreased since the '70s and '80s, but the emergence of known cases has been rapidly increasing, due to the fact that most people don't know they have it until it's serious damaged their liver for quite a long time.
posted by markkraft at 4:47 AM on March 17, 2013


I just completed the Interferon/Ribovirin combination therapy for Genotype 3a at Christmas.

Ask me anything.
posted by PeterMcDermott at 4:47 AM on March 17, 2013 [3 favorites]


Ok...

What was the experience like? How long did it take? Did it work? How are you doing now? Any lingering effects from the treatment?
posted by markkraft at 4:56 AM on March 17, 2013


I think leading with the headline that Hep. C has been cured is misleading.
posted by rosswald at 4:57 AM on March 17, 2013 [2 favorites]


"I think leading with the headline that Hep. C has been cured is misleading."

I can understand that, and the need to approach the issue cautiously, although two different tests on humans would suggest otherwise. That, and I was also trying to accurately represent the main link to hepc-cured.com, leaving it to others to read more and make their own determination.

Of course, Hep-C hasn't been cured at all, in any real sense, for a variety of reasons. It's been potentially cured, but unfortunately, they've been failed on many levels.

I've tried to express that as well. But I can absolutely understand the sheer frustration of those who are left waiting for what appears to be a dramatically better treatment regimen for their potentially fatal disease. I don't feel it's really my place to try to blunt their obvious anger or potential biases on the issue, so long as I lay out the basic facts.
posted by markkraft at 5:06 AM on March 17, 2013 [1 favorite]


What was the experience like?

Considering what I'd been told to expect, it was a breeze. The first month I was kinda tired, and I had some nausea a couple of days a week, but I don't think it was ever as bad as women with morning sickness have it.

That said, the nurses who supervised my treatment said that I was unusual in my lack of side effects -- most people don't have it as easy as I had it. But I help facilitate a local Hep C support group (something I was already doing before I had my diagnosis), so I already knew how much it varied.

I think the worst thing is when you have poor mood, but antidepressants work quite well for that.

How long did it take?

It depends on the genotype. I was fortunate and had 3a which just needs 24 weeks. People with genotype 1 tend to need 48 weeks and the success rate is much smaller.

Did it work?

Probably. There was no trace of the virus a month into treatment, none at three months, and none a month after completing. But they like to wait until six months after treatment before giving you the all clear.

How are you doing now?

Here's a weird thing. I actually felt better during the treatment than I had before. And I wasn't really ill. No liver damage that they could detect, apart from a bit of fattiness which is consistent with someone of my age and lifestyle.

But I'd been eating and sleeping poorly for years, growing forgetful, tired, etc. All things that I'd just associated with old age.

I'd been tested for Hep C. back in 1993 and was sure I hadn't put myself at risk since then, but my doctor had been harrassing me to do middle aged man health tests, and when I conceded, she also said, 'shall I do BBV's as well', so I was like, OK, go ahead -- why not?

Not thinking for a moment I'd test positive.

When your doctor calls you personally during the Christmas holidays, you know it isn't good.

So I had some apprehension about it, but I just thought 'if it's as appalling as people claim, I can always just stop the treatment'. But it was really manageable. I missed a couple of days work, but had it been critical, I could have always made it in.

I did flood Bootle Town Hall with my vomit on a few occasions though. And forgot to mention it to the cleaning staff.

And in the first month, driving back from the hospital, I fell asleep at traffic lights and my automatic car drove into the car in front.

Any lingering effects from the treatment

No, I was still nauseous for about a month after I stopped taking the meds, and the nursing team who supervised it said I still had some minor anemia, but I feel much better than I did before I did the treatment.
posted by PeterMcDermott at 5:18 AM on March 17, 2013 [18 favorites]


While this is indeed a narrative editorial staff have wet dreams about, the truth is as usual a lot more messy and uncertain. This is a drug combination that appeared to have significant efficacy in a trail designed to asses safety making it a very promising candidate for standard treatment, but the Phase III trail with the statistical significance to meaningfully say whether or not it can cure Hep C, as well as how well, has not been done. This is what people are pissed is not being done. It is not entirely clear what Gillead has up its sleeve that makes it so confident that it can beat out Bristol-Myers-Squibb and the other players they will likely now partner with, but there is good reason to suspect that the paths they're panning on taking towards a functional cure for Hep C are not significantly slower or worse than this now outdated partnership's.

Sitting on the edge of scientific discovery is a really weird and mind warping kind of experience that leads to all kinds of non-intuitive ways of thinking when you see where you are clearly. Even if this were to turn out to be a functional cure for Hep C that is not what it currently is, at the moment it is just a potentially promising path that is being abandoned for what will now be a field of competing promising paths - which in a lot of ways is a lot better for people who will be wanting to address their Hep C in the next few years even if it takes a little bit longer to get there.
posted by Blasdelb at 5:21 AM on March 17, 2013 [1 favorite]


"I feel much better than I did before I did the treatment."
Wow. Thank you so much for that.

I think part of the reason that more hasn't been done is that there's a bit of a stigma that many attach to hep-C. I think a lot of people hear hepatitis-C and think "drugs"... but they don't think transfusions, or monogamous gay males, or piercings, or tattoos, or acupuncture, or nurses who get exposed in the course of their work, or sex, or all kinds of potential ways to have blood-to-blood exposure.

Finally, I have a good excuse to tell my girlfriend to stop running off with my nail clippers.
posted by markkraft at 5:22 AM on March 17, 2013


From what I've been able to determine, both Sofosbuvir and Daclatasvir are currently undergoing Phase III trials. It seems possible that both will obtain FDA approval, either individually or in combination with other drugs, if not together.

If Sofosbuvir and Daclatasvir together are a very effective treatment for Hepatitis C, once Sofosbuvir and Daclatasvir are FDA approved, won't doctors be able to prescribe them off-label in combination to treat Hepatitis C? For that matter, once FDA approved, any third-party with sufficient resources could persue FDA approval for a treatment combining Sofosbuvir and Daclatasvir, irrespective of Gilead's intransigence, right?
posted by RichardP at 5:26 AM on March 17, 2013 [1 favorite]


To be fair, it was really hard to get treatment here in the UK prior to about 2008 when NICE issued guidance on the matter. Because it was expensive and liver units didn't have a specific budget for it, they set up all manner of arbitrary hoops that you'd have to jump though to qualify.

Now though, they've figured out it's going to be a damn sight cheaper to treat it now than it will be to treat all that liver disease down the line.

One last thing: when I started working with the organisation I currently work for -- about six or seven years ago, I had a colleague who had a Hep C diagnosis. When I asked him what he was doing about it, he said 'complementary therapy' (Chinese herbs, milk thistle and large lashings of strong marijuana was my suspicion.)

Anyway, when I started my treatment and he heard how manageable it was for me, he went back to see a specialist to do something about his condition. At which point he was told that it was too late for treatment and they expected him to need a liver transplant in six months or so.
posted by PeterMcDermott at 5:31 AM on March 17, 2013 [4 favorites]


"If Sofosbuvir and Daclatasvir together are a very effective treatment for Hepatitis C, once Sofosbuvir and Daclatasvir are FDA approved, won't doctors be able to prescribe them off-label in combination to treat Hepatitis C?"

If you notice, the Sofosbuvir trial is with the toxic Ribavirin. Gilliad is also pursuing trials with other drugs they have in the pipeline.

Basically, they could come up with a trial that gives them excellent results, and then bundle them together in a proprietary drug combination, effectively making it useless to prescribe them with anything else that would work just as well.
posted by markkraft at 5:32 AM on March 17, 2013 [1 favorite]


I wonder how much this treatment would cost in the US. Not infected & just curious about its accessibility.
posted by crapmatic at 5:37 AM on March 17, 2013


Thanks Mark, I hadn't considered the possibility that if the time comes that Sofosbuvir is made available by Gilliad that the only formulation available from Gilliad might be a formulation that combines it with another drug.
posted by RichardP at 5:39 AM on March 17, 2013


If you notice, the Sofosbuvir trial is with the toxic Ribavirin. Gilliad is also pursuing trials with other drugs they have in the pipeline.

There are two Phase III trials with Sofosbuvir going on currently, one is with Sofosbuvir alone and the other is with Ribavirin along with a variety of other Phase II trials with other compounds. If Gilead (with one l for those looking for more information) were to only market Sofosbuvir with Ribavirin even if it were shown to be effective alone or with other drugs that really would be a scandal, however that has not happened and is unlikely to ever happen.
posted by Blasdelb at 5:44 AM on March 17, 2013


[A couple of edits as per OP, to fix up the intro to "possible" cure, and replace the original link to a petition site. Thanks, markkraft.]
posted by taz at 5:47 AM on March 17, 2013


Clinicaltrials.gov is an awesome and convenient resource for fact checking by the way. Most everything tested on humans and related to the United States is required to be registered there.
posted by Blasdelb at 5:48 AM on March 17, 2013 [4 favorites]


I wonder how much this treatment would cost in the US.

I can tell you about the cost of the drugs in the UK. 24 weeks of combination therapy costs the NHS about £7,000. But that's just for the drugs. You'd need to add on the cost of the extensive monthly bloodwork, fibroscan testing, liver biopsy (if necessary) and the medical staff.

I'd bet you'd be hard pressed to do for less than $25,000.
posted by PeterMcDermott at 5:49 AM on March 17, 2013 [1 favorite]


Multiply that by 4 is my guess.
posted by unSane at 5:56 AM on March 17, 2013


*shivers* Things like Hep-C are one of the few things that make me glad I have to have so many regular blood tests for liver and other organ functions. I've had both the Hep-A and Hep-B jabs and boosters over the years, because several of my medications place me in a position where I can't risk it in the long term. But there are still really frightening things out there, like this, and to hear this sort of bullshit between pharma companies makes me ANGRY.

Surely some bright cookie somewhere should be contemplating taking these companies to trial in the EU Human Rights courts? Surely?
posted by strixus at 5:58 AM on March 17, 2013 [1 favorite]


" If Gilead . . . were to only market Sofosbuvir with Ribavirin even if it were shown to be effective alone or with other drugs that really would be a scandal, however that has not happened and is unlikely to ever happen."

What if they delay trials by over a year, in order to try making a proprietary combination drug of their own using a spanking new proprietary drug similar to Bristol-Myers' Daclatasvir and Johnson & Johnson's Simeprevir?

Because according to this news report, that's exactly what they're trying to do. If they're hedging their bets by also testing their cocktail with the highly toxic Ribavirin, it's because they don't know whether their new antiviral actually works yet. It hasn't been tested to the degree that either of the two other drugs have.
posted by markkraft at 6:33 AM on March 17, 2013 [1 favorite]


markkraft, Clinical trials get pretty confusing.

Drug testing in people most standardly gets done in three phases, though with various permutations of mixing and splitting them possible for various reasons. A Phase I trail involves giving the drug to a small number of people, usually healthy, and monitoring them very closely to make sure that it doesn't hurt them. Phase II trials involve giving the drug to a larger number of people and then monitoring them very closely in much the same way but with a more statistically significant population that could detect more rare side effects. Phase III trials usually involve an even larger number of people who are also monitored for side-effects but in a study primarily designed to assess efficacy, which require more people, to make sure the damn thing actually works.

You are right to say that they don't know that their new drug actually works yet, no one does, it hasn't yet been tested in such a way as to meaningfully demonstrate that it does work. The same goes for the other two front runner drugs and the various other ones trying to catch up. New drugs aren't being delayed here at all just perhaps Bristol-Mayers-Squibb (BMS)'s return on investment, the Phase III trials that are happening now will take a fuck of a long time because that is what Pase III trials do - 2014 is a reasonable target, the Phase III trials that aren't happening would similarly have taken a fuck of a long time because that is what Phase III do, and should for that matter. What Gilead is doing here is giving up on what would likely be a monopoly on the market (huge pot of money) that it would have to negotiate with BMS to split in exchange for a more open market that it thinks it can win in. They are currently testing Sofosbuvir alone in a Phase III trial, which is ideal for patients as it means that it will either be demonstrated to have efficacy or not. It is similarly a good thing they are hedging their bets with a second set of Phase III trials to see if Sofosbuvir can improve the efficacy of Ribavirin in case the effects it has are only subtle. To be clear this is not testing any cocktail's effect on the efficacy of Ribavirin but just Sofosbuvir alone.

If Sofosbuvir is indeed effective there will really be nothing stopping doctors from using it combination with BMS's drug if BMS can demonstrate their drugs efficacy. Assuming all of the efficacy is real, which hey has not yet been demonstrated, the biggest effect this refusal to work with BMS would have would be on BMS's ability to sell their drug to shareholders and market it in a monopolistic fashion. Gilead also have a Phase III trial planned but not yet registered to asses the efficacy of a cocktail of Sofosbuvir with ledipasvir, an apparently promising drug that they have in their pipeline that will undoubtedly take longer than 2014 to complete. That would then be competing with the market that will exist then with each of the various frontrunners then either in use or not in whatever kinds of combinations doctors then fancy based on evidence then available.

There is a decent case to be made that, we're we to live in a star trek utopia, the combined trial that is not happing in favor of separate trials would be better in a few subtle ways - but really I'm mostly just curious about how much BMS money is behind all of this outrage.
posted by Blasdelb at 7:33 AM on March 17, 2013 [3 favorites]


To be clear, just because these drugs aren't being tested together does not mean that doctors could not use them together if both drugs do indeed work.
posted by Blasdelb at 7:35 AM on March 17, 2013


the highly toxic Ribavirin
posted by markkraft


Everything you say about Ribavirin is correct, but also: Google search ribavirin gold standard
posted by rosswald at 8:00 AM on March 17, 2013


"If Sofosbuvir is indeed effective there will really be nothing stopping doctors from using it combination with BMS's drug if BMS can demonstrate their drugs efficacy."

...unless, as Gilliad have themselves said, they intend to combine it into a single pill with another drug, in a combination which is comparatively effective. This could not only serve to keep Sofosbuvir off the market for longer, it also would prevent doctors from being able to justify offering it as a part of a drug cocktail with drugs from other manufacturers that have been shown to work with it.

"You are right to say that they don't know that their new drug actually works yet, no one does, it hasn't yet been tested in such a way as to meaningfully demonstrate that it does work. The same goes for the other two front runner drugs"

You fail to point out the obvious differences here.

Sofosbuvir has been shown to work exceptionally well with Daclatasvir, for example, and Daclatasvir has also been shown to significantly improve performance of the current leading standard of treatment.

Similarly, Sofosbuvir has also been shown to work exceptionally well with Simeprevir, and to boost performance of the leading standard of treatment.

Really, that's a lot more testing and a lot more direct evidence than the new proprietary anti-viral that Gilliad is testing with.

The suggestion that they, by taking the time to come up with a single, proprietary pill, are somehow saving time just doesn't hold water, or have any evidence to support it.
posted by markkraft at 8:31 AM on March 17, 2013


[markkraft, at this point you need to stop threadsitting. This post is already borderline too axe-grindy as framed, and your repeated comments are not making it seem less so.]
posted by LobsterMitten at 8:40 AM on March 17, 2013


It's Gilead, with one L. My career is in this field. Don't blame a company for doing something that seems evil. Blame capitalism and the need to keep stock prices high. I can attest that Gilead spends the money to make things right. I suspect that the whole story is not available publicly.
posted by kamikazegopher at 9:26 AM on March 17, 2013


"This could not only serve to keep Sofosbuvir off the market for longer, it also would prevent doctors from being able to justify offering it as a part of a drug cocktail with drugs from other manufacturers that have been shown to work with it."

This is manifestly not the case. Assuming both drugs work individually, the Phase IIa safety conclusions and preliminary efficacy data supporting them in combination that already exist should be way more than enough to justify using them both in a cocktail as two pills - the only thing that is changed is that neither company would be able to market this specific cocktail which, assuming a cocktail still makes sense in light of future evidence, will not stop anybody. This is particularly among physicians who already have the parallels with treating HIV right in front of them. There is a lot of hoopla about this over the internet and all the pieces that make this absurd assumption and a few other distinctive mistakes seem to come back to here, which is a very media savvy and aggressive failure to comprehend the pharmaceutical industry, how it works, or what it is currently doing - sprinkled with vague woo language. Just read to the end of the New York Times link in the FPP if you won't believe me.

"The suggestion that they, by taking the time to come up with a single, proprietary pill, are somehow saving time just doesn't hold water, or have any evidence to support it."

For starters all of these pills are proprietary and all of the ones that work will make somebody rich - who is largely immaterial to patients, what is really important here. The timelines here are confusing even to people familiar with this kind of work but would be especially so if you are only going by investor boilerplate. There are currently right now two sets of Phase III clinical trials looking at the efficacy of Sofosbuvir alone and Sofosbuvir in combination with the current gold standard, what is being abandoned is a third set of trials that were never started looking at the efficacy of Sofosbuvir in combination Bristol-Myers Squibb's proprietary drug Daclatasvir that would have necessarily been completed some time later. Gilead is not going to withhold Sofosbuvir for a year or two once it gets approved, if it does, while it waits for its own other drug. They are going to put it on the market as soon as it becomes available and make tons of money.

"I suspect that the whole story is not available publicly."

With this kind of shit it rarely is.
posted by Blasdelb at 10:22 AM on March 17, 2013


Thanks to PeterMcDermott for contributing his knowledge and experience to this thread.
posted by Blazecock Pileon at 10:45 AM on March 17, 2013 [2 favorites]


There is a lot of hoopla about this over the internet and all the pieces that make this absurd assumption and a few other distinctive mistakes seem to come back to here.

Apparently, the woman behind it is Margaret Dudley and she's posted her story here.

Kinda curious, because she's got Genotype 3a as well -- the same strain I have/had. She was diagnosed in Sept. 2011, about three months before I was. It seems she was scheduled to take part in one of the trials, and is now pissed off because she can't get in -- though she's got an 80% chance of cure using the current treatment.

The lack of scepticism about drug company funded research is also kind of odd. I'd prescribe a large dose of Ben Goldacre's Bad Pharma for that condition.
posted by PeterMcDermott at 11:01 AM on March 17, 2013


It is not unheard of for governments to revoke pharmaceutical patents when companies abuse their market positions. It appears that India has already done this for another Hep. C medicine.
posted by Blazecock Pileon at 11:48 AM on March 17, 2013


I'm trying to figure out a "capitalism" reason for Gilead to be doing this and I'm kind of drawing a blank. Every day they spend noodling around on their mystery treatment is one day of Sofosbuvir's patent lifetime. That's real money they're not getting, and never going to get. Every day. Even if they come up with a combination treatment they can charge more for, a better weasely "capitalism" strategy would be to get your drug on the market, then come out with the combination drug and then steer everyone onto that so that by time the original goes off patent, everyone is one your patented combo pill and can't really substitute the generic.

I suspect someone thinks they have something magical in their pipeline. If I had a dollar for everyone who ever thought that before their drug went down in flames during clinical testing I'd use that money to start my own pharmaceutical company.
posted by Kid Charlemagne at 6:42 PM on March 17, 2013 [1 favorite]


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