Real Harvoni and Generic Harvoni

I had an email today asking about the differences between Generic Harvoni and the “real” Harvoni and thought that I should share my answer in my blog:

Firstly you should understand that there is ‘real’ Harvoni that costs around $80,000 and generic Harvoni costs about US$1,100.

There are three types of generic Harvoni, licensed unlicensed and APIs.

“Real” Harvoni is a combination of Sofosbuvir 400 mg and Ledipasvir 90 mg in one tablet. There are probably some other ingredients included in the tablet that assist with absorption of the Ledipasvir, which is slightly insoluble. Licensed generic Harvoni includes exactly the same ingredients as “real” Harvoni.

1. The licensed generic Harvoni.

This is made in India by four licensed manufacturers who pay Gilead a royalty for everything they sell.

The four licensed manufacturers are Hetero Pharmaceuticals, Natco, Cipla and Mylan. However of these four only two actually manufacture the active ingredients (APIs). These two are Hetero and Natco. The other two licensed manufacturers buy the APIs (Active Pharmaceutical Ingredients) from Hetero and Natco and just make them into tablets.

However these four licensed manufacturers all pay a royalty to Gilead and in exchange for that royalty Gilead has provided them with all the intellectual property to make Harvoni exactly the same as the Gilead version. The reason Gilead did this is because India did not grant Gilead a patent so these big Indian pharmaceutical companies would made a generic Harvoni anyway. By providing a license and getting a royalty gilead has been able to make huge profits from the Indian generic Harvoni production.

So in the case of the licensed generic Harvoni the product is IDENTICAL to the ‘real’ Harvoni because part of the license agreement and the reason the royalty is paid, is that Gilead gave these four companies all the intellectual property and manufacturing technology. So the licensed generics are identical to Harvoni. The only difference is the price.

2. Unlicensed generics. There are several sources of unlicensed generic Harvoni, these include to companies in Bangladesh. Incepta is the most well known and makes Twinvir. Another Bangladeshi company called Beacon makes both generic Harvoni and also Darvoni. Darvoni is a combination of Sofosbuvir and Daclatasvir in one tablet and is not a generic Harvoni but is an effective and cheap treatment for all Hep C genotypes including G1.

They both make unlicensed versions of Harvoni using APIs imported from China. Whilst the chemical content of the active ingredient (sofosbuvir 400 mg and ledipasvir 90 mg) is the same we do not know that technology to improve the absorption of Ledipasvir is the same as in Harvoni (Ledipasvir is not very soluble)

Another source of unlicensed generic Harvoni is from Australia. Several Australian pharmacies use imported Chinese APIs purchased from an Australian government approved importer. These pharmacies are all well qualified and licensed and they provide the generic version of Harvoni in two separate capsules, one containing 400 mg of Sofosbuvir and the other containing 90 mg of Ledipasvir. These capsules are take at the same time.

Whilst recent tests results indicate that there is no significant difference in the cure rates between licensed generic Harvoni and unlicensed generic Harvoni I generally recommend that people use the licensed generics rather than the unlicensed generics. For even though the evidence indicates that cure rates are the same across the board… even if there is only one or two percent difference in the results it is important.

Of course there are other factors. The cost of unlicensed generic Harvoni is always going to be a little cheaper because no royalties are being paid. Perhaps the cost will by a couple of hundred dollars per treatment cheaper and this will be important for a lot of people.

Current Prices of Generic Hep C Medicines in India

When generic Harvoni was released in India in December 2015 the cost was around US$2,000 for a 12 week treatment however as production and competition increased the price has gradually dropped.

This week, in mid-July 2016 the cost of generic Harvoni in India dropped again and now generic Harvoni can be purchased in India for around US$1,000 or a little less. As with all products different brands and different suppliers have different prices but if you actually go to India yourself and purchase generic Harvoni, of any brand, you will not pay more than US$1,000 for a 12 week treatment of 84 tablets.

You may get it a fair bit cheaper too if you shop around however I would warn against buying “bargain” priced generic Harvoni. The two components of Harvoni, Sofosbuvir and Ledipasvir are “commodities” and they have a specific cost of manufacture and therefore a specific value, like petrol or computers. So if something is very cheap, if someone offers you a 12 weeks treatment of generic Harvoni for say US$450 then I would suggest extreme caution and suspicion. If it is too cheap there will be a reason.

Maybe fake, maybe past its expiry date.

It is not something that you want to buy from a suspect source. If you have gone to all the trouble of traveling to India buy from a reliable supplier not a back alley dude.

There is no point in saving a couple of hundred dollars and discovering that your meds have past their expiry date or something worse. Pay the right price and get the right meds.

Now what I have just written applies to generic Harvoni. The cost of a 12 week treatment of generic Sofosbuvir is basically the same as a treatment of generic Harvoni.

If you travel to India and buy from a reliable supplier then you should expect to pay around US$1,000 for a 12 weeks supply of licensed generic Sofosbuvir and Daclatasvir. These will come in separate tablets so you will get 84 tablets of Sofosbuvir and 84 tablets of Daclatasvir.

Lastly please remember that these prices are if you go to India and purchase in India and carry your medicines home with you. If you want to have generic Harvoni or Sofosbuvir + Daclatasvir sent to you by mail or by courier then you will obviously have to pay more.

The most you should pay to have a 12 week treatment of generic Harvoni sent to you by door to door courier is US$1,200. The same will apply to Sofosbuvir and Daclatasvir.

If you have any questions about what option is better for you, or how things work in your country please feel free to email me. I supply complete support and advice completely free of charge

The Hepatitis C Virus is treated with equal effect by generic or non-generic Harvoni

28th July 2016: The ‘R’ Word: The Sad Reality of Relapse

The issue of relapse after treatment with the new Hep C drugs like Harvoni is not much discussed, I guess because we like to focus on the positive, the incredible cure rates, the happy news of another person reaching SVR 12 or SVR 24.

Yet whilst the new Hepatitis C treatment using Direct Acting Antiviral drugs (DAAs) has given incredible cure results for vast numbers of people with Hepatitis C the sad reality is that about one person in every 33 people who start treating their Hep C with the new DAAs will relapse after their treatment ends.

It does not matter if the treatment was with generic Hep C meds like Safino-L or Ledifos or Darvoni or the brand versions like Harvoni or Sovaldi the relapse rate is the same. The success rate for all genotypes except genotype 3 is about 96%. Hepatitis C genotype 3 has a slightly lower success rate of about 90%.

So the big question is: “”Why does one person relapse when the other 33 did not?””

This is literally the billion dollar question.

It is a big question for me, having completed successful treatment, having gone through the waiting period of wondering if I had cleared. The anxiety after the blood test to see if I had cleared the virus and waiting to hear the results. The 4 week blood test, the blood test at the end of treatment and the blood test 12 weeks after the end of treatment.

With every test was the anxiety. Particularly waiting for the results of 12 weeks after end of treatment blood tests. This is the SVR 12 test. If a person has no detectable virus in their blood 12 weeks after the end of treatment they are officially cured.

Its a big thing, and a big relief if you get the good news.. If you are clear 12 weeks after the end of treatment then you are cured, but if the virus has come back then you are shattered.

That is what I want to talk about in this post. I want to talk about relapses because for every 30 or so people who send me a joyful, exuberant email telling me they are clear I get one email telling me the sender has relapsed.

And it breaks my heart.

The reality is that there are a number of possible reasons for a person with Hep C to relapse but no-one knows exactly why some people relapse and others don’t, all we know is that there are a number of factors that could cause a person to relapse.

So what is relapse? What does it mean?

Well basically to relapse means that the treatment did not kill every Hep C virus in your body. That hidden somewhere in your body, usually in scar tissue in the liver, one or two or three virus remained alive, the medicines did not reach them where they hid.

When treatment ends and the DAAs leave your system these few remaining virus start to reproduce again and very quickly their numbers will rebuild. In the 12 weeks between end of treatment and the SVR 12 test virus numbers can go from undetectable to 3 million virus in a unit of blood. That is billions and billions of virus once more living in your blood.

So a person can have undetectable levels of virus from as early as week four of treatment but if just one hidden pocket of virus remains when treatment stops then a relapse will almost always result. (not always be usually).

What are the causes of relapse?

As mentioned this is the big question. Certainly people with severe cirrhosis seem more likely to relapse. For this reason it has become a common practice by specialist doctors to extend the length of treatment time for people with severe cirrhosis. Usually people with cirrhosis require 24 weeks treatment not the normal 12 weeks.

Because cirrhosis involves scar tissue in the liver the virus can live in the scar tissue where the DAAs have difficulty reaching because there is very little blood circulation in scar tissue.

The Hep C medicines are carried in your blood, where there is not much blood flow then the drugs do not saturate the tissue easily.

So if you have cirrhosis you should discuss with your doctor whether you might need a slightly longer treatment.

This is certainly the case for genotype 3, which has proven the hardest Hep C genotype to remove.

But there may be other causes for relapse as well.

One of these is UNDERDOSING, the opposite of overdosing.

Harvoni and Magnesium

Sofosbuvir and Ledipasvir (Harvoni) and Daclatasvir are both absorbed primarily in the stomach.

Sofosbuvir is quite soluble, it dissolves easily in the stomach, same for Daclatasvir. However Ledipasvir does not dissolve easily. It does dissolve but not easily. For this reason Gilead advises against taking antacid within 4 hours before or after taking Harvoni. So an 8 hour period where no antacid should be taken.

Below is the exact warning from Gilead:

“Avoid taking an antacid within 4 hours before or 4 hours after you take Harvoni. This especially includes antacids that contain aluminum or magnesium (Acid Gone, Aldroxicon, Alternagel, Di-Gel, Gaviscon, Gelusil, Genaton, Maalox, Maldroxal, Milk of Magnesia, Mintox, Mylagen, Mylanta, Pepcid Complete, Rolaids, Rulox, and others”

It seems likely that that stomach acid assists in making the Ledipasvir soluble and that anything that neutralises the stomach acid might reduce the amount of Ledipasvir that the body absorbs, possibly resulting in an underdose of Ledipasvir.

You will notice a heavy emphasis on not consuming magnesium, interestingly the world famous Mayo Clinic also suggests avoiding magnesium during treatment with Harvoni.

In the past couple of months I have begun the habit of asking people who have written to me telling me that they have relapsed if they are taking any dietary supplements. Several of them have responded that they have been taking magnesium supplements.

Now whether this is a factor in their relapse of not I do not know but it is worth considering.

Taurine, Caffeine and Daclatasvir

In my post on 21st February 2016 I discussed the discovery of Dr James Freeman that taurine, a common ingredient in energy and body building drinks, affects the absorption of Daclatasvir, because Taurine modulates induction of an enzyme called cytochrome P450 3A4 mRNA by rifampicin in the HepG2 cell line.

In plain English this article tells us that Taurine increases the levels of the enzyme CYP3A4. This is the enzyme that removes Daclatasvir from your system – in other words if you are consuming Taurine the effect is like you’re taking a 1/2 dose, or maybe even a 1/4 dose of Daclatasvir because taurine will reduce the affect of Daclatasvir significantly!

This in turn will mean that your chances of clearing the virus are reduced significantly.

Now taurine may not be the only thing that causes the body to remove Daclatasvir at increased rates, each and every “… extract” will contain dozens of chemicals, all of which might induce or inhibit CYP3A4.

For example the body uses the enzyme cytochrome to break down caffeine so it might be that high levels of coffee consumption causes elevated cytochrome levels that in turn will effect the amount of Daclatasvir the body can use.

One of the things that ties in with relapse is the slow responder.

I was contacted by a lady today who is a slow responder using generic Harvoni and had not reached undetected by 8 weeks. I asked her if she was taking any supplements or other medication and the only medication she is taking is a sleeping tablet, Zopiclone.

Interestingly when I googled Zopiclone + Harvoni I found a paper immediately that mentioned the CYP enzymes again. (Remember CYP3A4 which is the villain for Daclatasvir)

Zopiclone is also metabolized predominantly by CYP3A4 and to a lesser degree by CYP2C8 and CYP2C9. Zopiclone concentrations may theoretically be increased by DAAs and require close monitoring. Most other benzodiazepines should be used cautiously in patients on DAAs. Clinicians may consider starting with a decreased benzodiazepine dose and monitoring for benzodiazepine-related toxicity, or selecting an alternate agent such as lorazepam, oxazepam or temazepam. Dose reductions are also recommended in patients with severe liver impairment as per product monographs

I posted this information in the Facebook group Hepatitis C Treatment w/o Borders and almost immediately got a comment from another person who was a slow responder and had relapsed. The only other medication she was taking during treatment was also Zopiclone!

Perhaps a coincidence? Perhaps not?

But here are those same enzymes again and it seems that maybe we need to be much more aware of drug interactions when using DAAs… particularly if there are issues with side effects and slow responding.

Conclusion

So what does all this mean. Basically avoid food supplements and “energy drinks” during treatment. Avoid magnesium and antacids. Closely consult with your doctor about possible drug interactions that might occur while you are treating your Hep C.

Avoid taurine and excess caffeine. (I am not saying stop drinking coffee but keep it to a minimum during treatment just in case.)

We only get one clear hit at Hep C treatment and we want to optimize our chances of clearing this virus so it is better to be safe than sorry.

If a person relapses there are still treatment options but lets see if we can avoid relapse and having to go through all that again!!!

29th July 2016

How Things Change… More Good News From Britain

Here is more proof that Things Change if we keep working on it and things in the UK have changed a lot and are changing fast in the best possible way.

Over the past six months a small group of people including Dr Andrew Hill, David Crowley and other activists have been talking to doctors and people within the British Health Ministry about the importance and usefulness of generic Hep C treatment. They ah have shown the great advantage in the cost of using generic Harvoni and other generic treatments and also the effectiveness.

At the same time these same people have been bringing the issues surrounding Hep C treatment to the British news media and have succeeded in getting some serious news coverage on the issues.

All this effort has brought about great results.

Six months ago it was almost impossible to get monitored by a hospital in the UK if you we treating with generics now here is the list of SIX major London hospitals which will monitor people who are taking generic DAAs to treat their Hep C, and also one in Cambridge and one in Exeter.

St Mary’s Paddington

Chelsea and Westminster

Dean Street Clinic

Royal Free hospital

Barts

Royal London

St Thomas hospital, Westminster

Addenbrokes, Cambridge

Exeter Rd&E

So you see it only takes a few dedicated people to keep pushing, a couple of intelligent health professionals and a bit of media attention and things start changing.

Once public and political awareness increases changes will happen.

So if you are in a country that prohibits the importation of generic Hep C meds try doing a bit of agitating.

Don’t rely on your so-call Hep C Advocacy groups, they are mostly pretty useless and most are getting big pay cheques from Big Pharma. Sad but true.

So you need to get a few dedicated people and stir up the news media. Do that and things will certainly change.

Good luck and if you want to do this please be assured that I will give you any assistance and support that I can.

8th August 2016

Truth, Deception and Misinformation

The last couple of weeks have been rather busy for me. Because of the work load from my Hep C activities I decided to suspend my PhD studies entirely for 12 months as the combined workload was just too much. So I’ve been running around filling in forms and seeing people to organise the 12 months off.

Now that the PhD is on hold I am able to direct my energy back to Hep C issues, for whilst I love the topic of my PhD ” Strange News; where truth and myths collide. ” and enjoy the research and study I also know that the needs of people with Hep C and helping them access affordable treatment is more important than my own personal interests.

One of the big things that made up my mind about taking this path of re-focusing on my Hep C activities was news from a friend with Hep C telling me that she had just been diagnosed with a major tumor in her liver and has been given only a couple of months to live.

Of course this upset me a lot and it has taken me a while to get my head around how it must feel to get this news.

Whilst such news is hard to grasp I can relate to it by a degree because only 16 months ago my own doctor told me he suspected that I had liver cancer. So I do understand it in a small way.

Now I would like to talk about this friend, whose name is Lynne.

Lynne was diagnosed with Hep C genotype 3 earlier this year. It was about the time I was in the UK and had returned from the EASL conference in Barcelona.

Of course Lynne was shattered by the news she had Hep C because she was otherwise in very good health. So being a very pro-active person she looked at all the options and decided to go the route of generic Sofosbuvir and Daclatasvir. By far the best treatment option for Hep C Genotype 3.

When she discussed this decision to use generic Sofosbuvir and Daclatasvir with her Doctor in the National Health Service she was told in no uncertain terms that if she did the generics then they would not monitor her treatment.

(Such arrogance appalls me!)

So there was a lot of discussion about this decision ( a decision which I personally think is both unethical and probably illegal) and Lynne decided to go the generic route anyway.

When the doctors heard this they then offered her a monitored treatment with Interferon and Sofosbuvir.

So, whilst it was not Lynne’s preferred option, and certainly not the best option, she decided to go that way because she wanted her treatment to be monitored.

(It was however the CHEAPEST option for the NHS)

The first week of treatment was okay for Lynne but by the second week the side effects from the Interferon were getting bad, by the fourth week the side effects were a nightmare.

But Lynne pushed on because she was determined to get rid of the Hep C virus and get her life back.

She is made of stern stuff is Lynne!

But here is the thing… Interferon is a highly toxic treatment. It is a treatment from the Dark Ages of medicine. It is toxic to the liver. Yes Interferon causes significant damage to the liver and other organs.

Dr James Freeman once said to me that using Interferon to treat Hepatitis C in the 21st century is like amputating an arm to treat gangrene. Sure it will cure the problem but the damage associated with the cure could be worse than the disease and there are much better options.

So Lynne completed her treatment, was pronounced virus free and then told that she had a massive tumor (which, as far as anyone was aware, was not there before she started treatment).

And she was told she had a just a couple of months to live.

So she has endured 3 months of horrendous Interferon therapy and then told she is going to die.

Now I am not saying that the Interferon caused the tumor however these concluding comments by Emeratis Professor Ronald Koretz M.D. in his excellent article about Interferon treatment entitled: Hepatitis C treatment (with Interferon): no benefits and possible harm certainly highlight the problems.

Concluding comment

Given the natural history of chronic hepatitis C, as well as what we know therapy accomplishes, it is very difficult to justify a policy for routinely treating such patients to prevent decompensated liver disease. The surrogate outcomes were not valid in the one occasion when validation information was available. The treatment has not been proven to be efficacious with regard to preventing clinically important disease, it is expensive, and it causes substantial morbidity (including death). It is an inappropriate clinical decision to prescribe a toxic therapy (especially an expensive one) that has never been shown to provide clinical benefit in properly-done randomized trials.

So Lynne’s doctor prescribed a treatment that is known to be highly toxic when another, much less toxic, treatment was readily available…

Why?

The reason is simple. This doctor had either been misinformed about the effectiveness of generics by the representatives of Big Pharma or was simply in the pocket of Big Pharma.

It is a very sad and disturbing outcome and one that I sadly hear of too often.

Would the results have been different if Lynne had used Sofosbuvir + Daclatasvir? Of course we do not know however we do know that Lynne’s doctor forced to take a sub-optimal treatment when a much better and safer treatment was available.

But here is another story; the opposite story.

In this next story, which I received by email today, the doctors refused to monitor the patient, refused to even see the patient if he used generic Harvoni to treat his Hep C.

But being in a country where health care is not free the doctor also could not offer the patient any alternative treatment at all. Not even Interferon.

So the patient contacted me and I assisted him to get generic Harvoni.

Here is the email:

Dear Greg,

Glad to hear from you. Florin’s treatment is not completed yet; should be done by 1st of September – and then it will take another week or so until the labs results are back. As soon as I get the results will complete the attachment and email it back to you.

There is a interesting story behind this, you might want to hear it.

Greg, I’m not aware of your belief system (or lack of it) and hope you are not going to be offended by my many references to my Christian faith.

My cousin is about 10 years older than I and we grew up not particular close. In the early 80s I left Romania and rarely kept in touch. About three years ago he called me to extend his sympathy for my mom passing. After a few minutes of small polite talk I thanked him for the call and wish him good health and fortune. Them he proceeded to say that he had HepC for more than 10 years and for the majority of the time he feels quite ill – his only wish was that it was a cure for this ailment. Told him how sorry I was and that I will pray for him.

A year or so went by when I heard that FDA approved a cure for HepC. I called my cousin and give him the good news; he was aware of it and that it costs 100 times more than his annual salary. I told that I do not have that kind of money but I will keep praying for him and not to give up hope. Hung up the phone and prayed that God will find a way for him to get the medication he needed.

Months went by and I almost forgot about this issue when I came across a Bloomberg News article about India making generic Harvoni and how people are getting the medication at a fraction of its US cost. I ran a Google search and found an Australian ABC news segment about a guy (you) who was cured using the generic medication from India and who now is helping others. I quickly Googled your name, found your blog and emailed you. I pray God again that this is not a scam and you will help me help my cousin. The next morning I saw an email from you saying that you could help and explained the process. I called my cousin in Romania a told him that God just answer my prayers and how I was planning help him. I also told him not to get his hope too high as nothing is certain in life.

Few weeks went by and I never received the prescription or the copy of his ID you needed so I called to see what the delay was all about. He told me that his doctor, who offered him no hope of a treatment or cure advised him against such treatment as most likely this is a scam – when he told the doctor that these meds are being provided to him at no cost, the doctor suggested that these meds are probably fake at best, and poisonous at worst. I was really upset and did all I could to convince him that this is all legit and have nothing to fear. He finally agree to send me a prescription and ID in order to forward them to you.

Drama did not ended here – after he received the meds from India his doctor refused to monitor his health during the treatment and he needed to ask several doctors until he found one in a private practice who agreed to help for a fee.

He is taking the meds since June 1st and the only side effects were some mild headaches, insomnia and increased irritability.

He is being seen by the new doctor once a month and all his blood and liver counts are now normal. For some strange reason, the MD did not wanted him to do mid treatment virus load count Anyway, in a few weeks I will know if the treatment worked and will pass the info to you.

It is wonderful that you are helping people in need and I do not have words to express my gratitude for your selfless act!

Sorry for being so long-winded, but wanted to share this with you.

Sincerely,

##########

I would like to end this post with the words that Lynne said to me when I asked permission to write about her story

Yes greg you can write about my story and tell people don’t wait for the NHS or for some health insurance to treat you, it may be too late. Beg or borrow the money to buy the generics …. you can use my name if u want x