Hep C Discussion Forum

Zlikster · Guru

RE: FDA Approves Gilead’s Sovaldi (Sofosbuvir)

Loopy Lisa · Guru

Thanks Karen, I was waiting to hear it had been approved in the US, I suspect january in Europe. I do believe the trail off drugs that follow in the next few years will eradicate Hep C. The real battle is people testing and having access to the drugs. Soon the toxic levels off drugs will be so short that they will have little effect in comparison to the warrier horse amount currently in use.

:D

Karen · Senior Member

Lengthy...but may be an interesting read for some.

Taking down Gilead seems to be beyond reach. The attempts have been repetitive but short of success. Gilead is a stallion. Unlike stallions, the horses whose muscular superiority over other horses is genetically derived, Gileads power is acquired through a unique culture that embraces the power of intuition, self-confidence, common sense and courage. Using an optimal amount of faith, the firm turned intuition into inspiration and using courage and wisdom, the Stallion carried out inspired tasks fated unattainable by others.

Thanks to the megastars contribution in the treatment of AIDS through its mega anti-retroviral pills, millions of desperate AIDS patients death sentences are being nullified. The use of multiple highly active antiretroviral therapy (HAART) turned the torturer and killer disease into a chronic disease, decreasing the patient's total HIV burden, preserving the immune systems function and avoiding the opportunistic infections that used to assume the killers role of AIDS victims before the HAART drugs.

Mentioning the firms intuition and insight in the beginning of this article was not meant as a crafted artistic text to just praise a firm, but a reality demonstrated in Gileads decisions in general. A well-illustrated inspired act, though, is Gileads decision to pay an obscene amount of money to buy Sovaldi (sofosbuvir) - the pill that the FDA granted approval a couple of days ago. Most Gileads fans, believed that the decision made no sense; especially that Gilead has its own drug discovery technology. As the drug was passing the tests of clinical trials and approaching approval, all those who disapproved of the firms decision realized how insightful was Gilead and how shortsighted they were.

Recalculating, we grasped the fact that millions of more hopeless HCV infected people who had declined to take previous treatments from fear of side effects will be willing to take the Sovaldi combination that would cure them in a 12-weeks. Assessing the cost of treatment while considering the cost of the untreated progressive HCV infection, the cost of the all-oral combination looked meager in comparison with the cost of the progressive disease, the complication of cirrhosis, including the hospitalization for hemorrhagic episodes, for liver transplant, the cost of transplant complications and of the possibility of HCV infection of the transplanted liver and of cancer. More important is avoiding the cost patients pay in their agony caused by intolerable symptoms, and caused by the expectation of cancer and death.

The Director of the Office of Antimicrobial Products in the FDAs drug evaluation center, seems to have stated, The approval of Sovaldi represents a significant shift in the treatment paradigm for some patients with chronic hepatitis C.

The sofosbuvir combo taken for 12 weeks cured 90 percent of patients with genotypes 1, 4, 5 and 6 who hadnt been treated before, Sovaldi is also approved for genotypes 2 and 3, which account for as many as 25 percent of infections, in combination with ribavirin.

The stallion has reached the finish line before the other horses. Lets not talk about other horses now. It is Gileads week. When the celebration ends, we will try to find another stallion among the other horses. We are sure we will find a few.

-- Edited by Karen on Monday 9th of December 2013 04:52:31 PM

Zlikster · Guru

cheers for explanation Malcolm :) seems Sofosbuvir is the magic bullet indeed...

just curious, what to you think might be best upcoming pangenomic DAA (inhibiting NS5A, NS3/4A) to go with Sofosbuvir (as NS5B blocker) as combo? Is it still Daclatasvir+Sofosbuvir best candidate?

tnx!

Tig · Admin

Malcolm, please tell me that you had that information written down and you copy/pasted it onto your post? If you wrote that from memory, let me be the first to say, "your memory is back, no more brain fog is apparent!" That explanation was way over my head, except for some of the small words, lol! It's a blessing to have members like yourself, Matt and the others that commit the time and energy to not only study, but learn and remember this complex data. Saying I'm impressed would be an understatement!

Loopy Lisa · Guru

I look forward to accessing this drug, it does make a world of difference side effects, and for most of us treatment niave a welcome escape from the hardcore SX that a lot on here has had to endure.

mallani · Guru

Hi Matt,

Don't believe 'only Sofosbuvir delivers active drug to the liver'. All DAA's are delivered to the liver by the portal vein and hepatic artery circulation. In fact Sofosbuvir is absorbed and presented to the liver as a phosohorylated nucleoside analogue, and inside the hepatocyte, it is converted into the active nucleoside triphosphate. As we've discussed, blood supply to the hepatocytes is compromised in cirrhosis.

Some basic Virology: If you think of viral replication, the NS3-4A protease is an enzyme that cleaves the viral polyprotein into 10 mature proteins. Next, these proteins are assembled into progeny RNA by the NS5B polymerase, under the guidance of NS5A.

Blocking the NS5B polymerase is an efficient way of blocking replication. However, NS5B is a very complex polyprotein. It is shaped like a closed R hand, and has sites named thumb, palm and finger. The active, highly conserved part is in the palm, and this is where Sofosbuvir binds. Being a nucleoside inhibitor, this very stable , and resistant to mutations. It is also common to all Genotypes, so nucleoside antipolymerases are pan-genomic.

Non-nucleoside antipolymerases do not block the active site, but attach to allosteric sites on NS5B, interfering with , but not actually blocking the polymerase. Examples are ABT-333, which are thought to be less effective and mutation prone.

It is interesting to note that normally, we do not have any RNA-dependant RNA polymerases in our bodies. Therefore blocking this site does not affect any tissues, so is free of side effects. This is very different to blocking a protease- we have many proteases in many tissues, which is why the antiproteases have an impressive list of side effects. Cheers.

Zlikster · Guru

Hey Matt, same here, tho i am getting obsessed with money game in big pharma...

Looking at Gilead history and their acquisitions. They bought Pharmasset for 10.4bil $, all other companies (11 of them) they have acquired cost em roughly 6.5bil $. Seems they really smelled out big money on Sofosbuvir. Projected sales of Sofosbuvir in first year up to 2bil $. That means in 5-6 years their ROI, after that they have cca 10 years more before patent expires to profit fully. Considering they could have bought Pharmasset for 3-4bil $, this just looks like insane lust for money from their side.

Hey Tazkat, i hope you get yourself in some nice clinical trial and get your liver back (in case your insurance won't cover Sofosbuvir) :)

TazKat · Senior Member

thank u mallani!!

TazKat · Senior Member

thanks guys.. maybe there will be hope. i go back to my hepatologist in march. in my last scan they saw a very small cyst on my pancreas. scared me!!! did a biopsy but was so small only got enough fluid to do one test. it was call pre maligment.. yea right? i was like what?? they said it could sit there & do absolutely nothing but will watch. i will have another ct scan in march too i think.. i am so tired of carrying this stuff around. i have been ok & then very depressed.. i have been juicing & was feeling better,then stopped but getting more kale , fruit & broccoli etc to start up jucing again.. but thank u again for answers & advice.. Merry Christmas!!

Matt Chris · Guru

Hey all

Was reading over Gilead's presentation to the FDA, seems it does have some interesting advantages over some of the other DAA's , check out this excerpt

Sofosbuvir: Clinical Pharmacology Profile

Sofosbuvir is an orally bioavailable nucleotide prodrug
Sofosbuvir is rapidly taken up by the liver
Long half-life (~18 h) for active triphosphate

Sofosbuvir (5%), GS-331007 (>90%) of systemic exposure
Only sofosbuvir delivers active drug to hepatocytes

My virology is very rudiment but it seems to me that if this statement that "only Sofosbuvir delivers the active drug to the hepatocytes" is true it has a great advantage over some of the other DAA's because the replication process of HCV takes place in the liver. Understanding the concept of how these DAA's inhibit viral replication is one thing, but the perceiving the significant difference between nukes and non-nukes and where and how the virus life cycled is ended by the different treatment approaches is beyond my limited knowledge. I guess having to wait for treatment again has me wanting to learn about the science and biology as part of the protocol to keep my obsession with understanding everything HCV

matt

Zlikster · Guru

c'mon China and India, do something (deny patents!) :) Sofosbuvir production ain't that complex. I don't wanna wait 15 years (cca 2029 i think?) when Gilead's patent on Sofosbuvir expires. My insurance would never cover that amount (24w of Sovaldi=168k $!!!). Heck they have only started to cover SoC Peg+Riba 3-4 years ago over here. They still can't afford Incivek (soon to be available they say, meh).

It will be interesting when others in next 2-3 years (Merck, Abbvie, BMS,etc) join the FDA approved drugs market...but until then Gilead will already "collect" *hitload of money (insert evil laugh here).

remindes me on South Park episode (w. Magic Johnson) where they discover a cure for AIDS. Ton of money, injected straight to body ;)

@Malcolm, i doubt any insurance co will let docs prescribe 24w for GT3s, which seems will be standard prescription for GT3. 168k $ is really insane amount for drug in form of a pill (sounds more like a decent amount for complex operation!).

mallani · Guru

Hi TazKat,

Sovaldi will be available for those who relapsed after previous Victrelis or Incivek Rx. One of our Members (JIme), did a successful Trial using Sovaldi after relapsing after Incivek, so RAV's are not a problem.

Suziq is also on a trial using Merck-5172 which is also effective against all known Incivek and Victrelis RAV's.

You have options now, so ask your doctor to get you started on Rx again- cirrhosis is no fun. Cheers.

suziq · Senior Member

Hi Tazkat

I think the Merck combo(C-Worthy) that I am doing as a clinical trial will go around any resistance built up by from previous treatment. I am really not sure about it, but think Mallani could give you a clear answer. He has medical knowledge, which I don't. I know that Merck has Breakthrough Status on this combo. Right now, I am near the end of the second part of the trial that is testing cirrhosis and null responders. EOT for this trial is Jan 3rd 2014.

SuziQ

-- Edited by suziq on Sunday 8th of December 2013 11:40:31 PM

Tig · Admin

Sorry to hear that you relapsed. That sucks... But you should be a candidate with the new medications. There has been a lot of discussion here recently about this sort of thing. Use the search function at the top of each page. You'll find references to it there. We have several others that will also comment on your question I'm sure. The studies with these new drugs has provided a lot of hope for all genotypes and levels of fibrosis. I would research ongoing clinical trials and see if there is one that you might qualify for. Ask your Hepatologist or GE if they have some info available. They often do. Keep in touch, good to see you again!

TazKat · Senior Member

i did the incivek & relapsed.. 2012.. already starting to cirrohis. (sp) u would think i would know to spell that by now lol can ppl like me to able to do this if i can? confuse

skewedButNotBroken · Senior Member

I'm sure I'm not the first one to think of this, but if India does start producing cheap generics I'll bet that tens of thousands of Americans will get a passport and go to India and pickup a 12 week supply for less than two hundred dollars. I won't comment on anything beyond this point, but I'm sure you get the picture.

Cheers,

JIme · Guru

I don't think these other companies are any different than Gilead. Although none of them, as far as I know, paid 11 billion for their drug.

Still it doesn't justify charging that much money.

lauralou57 · Senior Member

Yes, this is price is outrageous!

Gilead does have a good drug combination of sofosbuvir/ledipasvir with/without ribaviran for treament-experienced 1a's but the Bristol-Myers Squibb and AbbVie combination are giving SVR for over 90 percent also. There may be some other companies I have missed. I also believe both Bristol-Myers Squibb and Abbvie received breakthrough therapy designation from the FDA as Gilead did. If other companies besides Gilead are also going to have drugs FDA approved could this not affect the price?

Tig · Admin

Even if they do honor their assistance program, what percentage of people needing that kind of assistance will get enough help to complete a treatment program? I'm thankful for any attempts to help the less fortunate but I think the actual number of people helped will be woefully small. These BigPharma outfits only do this kind of thing as a way of gaining acceptance for their initial pricing structure. Somehow they think that this sort of community service program, that is easily covered by their gross profit levels anyway, shows their genuine concern for the unfortunate, when it's simply more smoke and mirrors...

suziq · Senior Member

Just curious, if Gilead has an assistance program, will it supply all the drugs for treatment or just their drug? Still a few clinical trials still out there--especially for genotype 1.

SuziQ

HR · Senior Member

I believe Malcom hits it square on the head. What are the insurance companies going to do?

They will be the deciding factor. It doesn't matter if the treatment is $40,000 or $84,000 most of us couldn't afford that either way. If you are lucky enough to have insurance we pray the insurance companies will let the patient use this drug. If no insurance we hope Gilead will honor their assistance program.

just my two cents

Tig · Admin

Thanks Jim, that's good information. Truth is if Gilead would simply cut their initial offering price in half or more, they would be able to provide the medication at no cost to untold numbers of patients and still be able to stuff hundreds of billions into their coffers. Greed has no limits however. But it's nice to see that someone there has given some consideration to the less fortunate.

JIme · Guru

This is from Vicky. Hopefully some people could qualify for this program.

Subject: Sofosbuvir Gilead Patient Assistance Program

U.S. Patient Assistance Program 
Gilead is committed to ensuring that people with hepatitis C can access
Sovaldi and has launched Support Path(tm) (www.MySupportPath.com) to provide
assistance to patients who are uninsured, underinsured or who need financial
assistance to pay for the medicine. The program consists of an integrated
offering of support services for patients and providers, including: 

*	Access to dedicated case managers to help patients and their
providers with insurance-related needs, including identifying alternative
coverage options such as federally-insured programs (e.g., Medicaid,
Medicare) and health exchanges.
*	Education and support, including a 24/7 nursing support service line
and the ability to schedule an onsite visit from a clinical educator.
*	The Sovaldi Co-pay Coupon Program, which provides co-pay assistance
for eligible patients with private insurance who need assistance paying for
out-of-pocket medication costs. Most patients will pay no more than $5 per
co-pay.  Co-pay assistance can also be applied toward deductibles and
co-insurance obligations.
*	Gilead will provide support to the Patient Access Network (PAN)
Foundation, an independent non-profit organization that provides assistance
for eligible federally-insured and privately-insured patients who need help
covering out-of-pocket medication costs.

*	The Support Path Patient Assistance Program will provide Sovaldi at
no charge for eligible patients with no other insurance options.

Information about how to apply for any of these forms of assistance can be
found at www.MySupportPath.com or by calling 1-855-7MyPath (1-855-769-7284)
between 9 a.m. - 8 p.m. EST.

Tig · Admin

Malcolm, considering the current level of turmoil throughout the healthcare system in the USA right now and the attempt to convert our system over to a single payer model, I know what will happen. The planned financial backbone of the new system being put into place hasn't developed at all. They counted on the funding from the healthy to care for the less healthy and indigent but it's not happening, at all. With the lack of available funds, you can see the writing on the wall in my opinion. They most certainly will go with the least expensive treatment plan, not because they want to, but because they have to.

mallani · Guru

Imagine the discussions in the USA Insurance Companies. 'Hmm, here we have a Geno 1 Rx -naive 45 yo with a low VL and no liver damage. Should we approve 24 weeks of Victrelis for $37,000 with a SVR chance of ~80%, or should we approve 12 weeks of Sovaldi for $84,000 with a SVR rate of ~90%?' .

mallani · Guru

Hi Jill,

Naturally I agree with all the comments, but there are no surprises here. I can't seem to find the Prescribing Information for Sovaldi. I wonder what the stopping rules are, and at what point do you need to be Undet. to continue. I also wonder about the 12 week duration for Geno 1 cirrhotics- this is a grey area, and it may be left up to the individual Hepatologist to decide if 12 weeks is enough.

The stated Phase 3 SVR rates are between 76 and 92%. I am confused by the statement 'no viral resistance to the drug was detected among patients who relapsed....'. Does this mean there are RAV's they can't identify, or is the drug not as effective as we are led to believe? RAV's are found in all Victrelis/ Incivek relapsers. I guess we need to wait for the magic ~100% SVR combo.

Gilead will now be able to add Ledipasvir to make a single Sovaldi/Ledip. pill, and they will price this at ~$1,300 per pill. This should stop any mix and matching with other DAA's (like Daclatasvir). Yep, Gilead want it all.

Cinnamon Girl · Guru

Yes, absolutely outrageous, Tig, and it`s hard to understand how Gilead think they can justify it. If it`s going to cost $84,000 for a 12 week course of one pill a day, that makes it $1,000 per pill!!! I was reading earlier that the AHF (AIDS Healthcare Foundation) have expressed `profound outrage` at Gilead over this proposed cost, and I wouldn`t be at all surprised if we see a lot more protests.

http://hcvadvocate.blogspot.ca/2013/12/ahf-gilead-outrage-on-hep-c-drug-price.html

Tig · Admin

Outrageous on the part of Gilead! I'm rooting for the powers that be in India and hope they stick to their guns and deny Gilead patent protection. They have shown proof that the $84000.00 12 week course price set by Gilead can be reproduced with a generic that costs less than $200.00!! I honestly don't know how the Gilead corporate board or it's legal department can look at themselves in the mirror. If their greed affected their families the way it has affected ours, they wouldn't be so ready to disregard price considerations for most affected by this disease. When 90% of those affected are lower income and in third world countries, these price attacks will have a profound effect on the chances of global HCV eradication. I would investigate whether there is some sort of criminal disregard charge that could be filed against Gilead for price gouging and fixing in general. Why would an intelligent person wake up one morning, with the power of life in their control and choose to deny it to millions, simply to stuff your corporate bank account? I guess beauty is only skin deep. Greed is an ugliness that goes to the bone...

Cinnamon Girl · Guru

Yes, I agree Jim, such a a shame Gilead pulled out of the collaboration with BMS that you were on, it seems like the $ rules all the way where BigPhama is concerned. It`s not all going well for Gilead though, they are being sued in the US by Idenex over patent infringement, and in India they are also facing a battle over getting patent protection. Here are the details...

http://hcvadvocate.blogspot.ca/2013/12/idenix-pharmaceuticals-files-patent.html

http://www.pharmatimes.com/Article/13-11-25/Gilead_responds_over_India_patent_pressure_on_HCV_drug.aspx

JIme · Guru

I don't know why it's not approved for G1. That was the trial we were on. 100% success.

84K will ceryainly keep many people from getting these drugs. It's a shame $ rules this world.

Cinnamon Girl · Guru

Hi Jim, genotypes 2 and 3 won`t need to take interferon, and this does open the way for future all-oral treatments for gen 1, for example using a sofosbuvir/ledipasvir combo. Ledispasvir could be approved by the end of next year, and there are also trials underway using sofosbuvir in combination with other treatment drugs, so this is definitely a significant step forward, although the cost is likely to be a major consideration.

Hi SusiQ, yes, I`m sure your trial coordinator is right about that. Note that people with gen 3 will have to do 24 weeks, which is what we expected following the improved results from the Valence trial.

JIme · Guru

What's the point if you still have to take interferon?

suziq · Senior Member

Gilead is right on schedule with their FDA approval. BUT, nothing yet approved without interferon for Genotype 1. However the shorter treatment times are a big improvement. And for Geno 2 and 3--it will be without interferon. My coordinator was saying Tuesday that the true efficacy of the new meds will be known when they begin to be used in general population. And that is now beginning for Gilead Sovaldi with the FDA approval. Let's hope this is just the first step of a new era for Hep C treatment and more meds will be approved during the coming year.

-- Edited by suziq on Saturday 7th of December 2013 02:49:00 PM

Cinnamon Girl · Guru

Dec. 6, 2013 - The US FDA has approved Sovaldi (sofosbuvir) 400 mg tablets, a once-daily oral nucleotide analog polymerase inhibitor for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen.

Sovaldi`s efficacy has been established in subjects with hepatitis C virus (HCV) genotypes 1, 2, 3 or 4 infection, including those with hepatocellular carcinoma meeting criteria (awaiting liver transplantation) and those with HCV/HIV-1 co-infection.

Gilead said Friday it would price the drug at $84,000 for one 12-week supply. Patients with a less common subtype of the disease may need to take the drug for 24 weeks, raising the cost to $168,000 for one course of treatment. Drugs already on the market run between $25,000 and $50,000 for a course of treatment.

Full details including recommended regimens and treatment duration...

http://hepatitiscnewdrugs.blogspot.co.uk/2013/12/hepatitis-c-gileads-sovaldi-sofosbuvir.html

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