Mabthera/rituximab from India/Israel

[Fred1234567]

Has anyone bought this drug from a "cheap source"???? If so would you mind sharing the how/where and the cost. Thanks.

 

[redo]

RTX is something which is given under supervision, often with monitors to your heart rate and more, and it's normal that you have to sleep over at the hospital just for precautions. It's very rare that something goes a rye, but if it does, one should be at a hospital.

RTX is available in India, and I guess one should have no problem convincing a doctor to dispense it. Although if I was to get it off label again, I'd probably go to Spain and get it off label there.

They have something called Reditux in India, although I have doubts that it's similar to RTX http://www.drreddys.com/products/popups/reditux.htm also written about it here: http://en.wikipedia.org/wiki/Reditux

 

[Sherlock]

RTX is something which is given under supervision, often with monitors to your heart rate and more, and it's normal that you have to sleep over at the hospital just for precautions. It's very rare that something goes a rye, but if it does, one should be at a hospital.

RTX is available in India, and I guess one should have no problem convincing a doctor to dispense it. Although if I was to get it off label again, I'd probably go to Spain and get it off label there.

They have something called Reditux in India, although I have doubts that it's similar to RTX http://www.drreddys.com/products/popups/reditux.htm also written about it here: http://en.wikipedia.org/wiki/Reditux

Thanks, I hadn't known about Indian RTX. Any relevant dissimilarity would likely be in it's Fab region - and therefore the epitope on CD20 that it binds to. IIRC, that also applies to the Humax fully-human anti-CD20 mab, and any other mab like the linear one under development somewhere.

It's said that MABs are very hard to produce, unlike ordinary pharmaceuticals. Yet OTOH you can buy MABs that are made for almost anything these days for laboratory testing, such as immuno-labeling. I'm thinking that the huge expense is really in the trials to prove them safe and effective for treatment in humans - so maybe they really can produce a safe and effective type of RTX in India. I wonder if they have government supervised post marketing adverse event reporting system there?

Why would you choose Spain?

Btw, I'd expect that getting a bad infusion reaction (aside from cases where the patient is not allergic to mice) would be more likely in cancer patients, simply because there are more B cells to kill and spill their contents. E.g. there is such a thing as tumor lysis syndrome, that wouldn't apply to CFS. But then again, longer term reactions in the immune-dysfunctioned don't apply to cancer patients as they might in CF - even in cancer Pts with secondary auto-immunity.

I did see a Canadian discount pharmacy selling the Reditux - I suspect that comes with free shipping

 

[Jacque]

All I know is personally I wouldn't put anything in my body from India...after watching a very special friend spend about 100K goin to India for Stem Cell Miracle treatment for Lyme and CFS... she Is NO better..and WORSE infact bc she picked up something in the Stem Cells... Been a while and I can't remember the details... So I will stick with what Dr. Kogelnik recommends (while it is free) ... and I agree i think the cost is bc of testing and trials they are doing...yet ... where I am confused is WTF can afford to pay it??? Mine would cost over 70k!!!!

 

[Snow Leopard]

The yearly cost of the drug in Australia is about $20k (two doses every six months, not including hospital stay), I agree that this is still unaffordable for most people (myself included).

 

[alex3619]

Hospital monitoring, or equivalent trained medical monitoring, is mandatory for this drug. An occasional patient has extreme reactions - in a hospital its easy to deal with, if you are far from quality care it could be life threatening.

I am hoping they can massively increase the rate of full recovery with this drug (no continuing treatment required). If so it will be easy to sell the idea to governments (and maybe insurance companies) that it should be subsidized. If not this will be a hard drug to convince anyone to subsidize.

Bye, Alex

 

[Jacque]

Wonder why they require a hosp stay there an not here in US? Is that 20K US? All of this illness, and the controversial motive$ behind it are all a mystery to me....:thumbdown:

 

[redo]

Thanks, I hadn't known about Indian RTX. Any relevant dissimilarity would likely be in it's Fab region - and therefore the epitope on CD20 that it binds to. IIRC, that also applies to the Humax fully-human anti-CD20 mab, and any other mab like the linear one under development somewhere.

It's said that MABs are very hard to produce, unlike ordinary pharmaceuticals. Yet OTOH you can buy MABs that are made for almost anything these days for laboratory testing, such as immuno-labeling. I'm thinking that the huge expense is really in the trials to prove them safe and effective for treatment in humans - so maybe they really can produce a safe and effective type of RTX in India. I wonder if they have government supervised post marketing adverse event reporting system there?

Why would you choose Spain?

Btw, I'd expect that getting a bad infusion reaction (aside from cases where the patient is not allergic to mice) would be more likely in cancer patients, simply because there are more B cells to kill and spill their contents. E.g. there is such a thing as tumor lysis syndrome, that wouldn't apply to CFS. But then again, longer term reactions in the immune-dysfunctioned don't apply to cancer patients as they might in CF - even in cancer Pts with secondary auto-immunity.

I did see a Canadian discount pharmacy selling the Reditux - I suspect that comes with free shipping

After the first Mella/Fluge study was released I searched around some on the net, and one thing I looked up was "custom monoclonal antibodies", and I was amazed to see how many there are out there. Just like you I noticed that although for research purposes, it seems like it's pretty straightforward to develop, and doesn't require some totally new approach to produce antibodies for any antigen out there.

Speaking of which, one of my hopes for the future are tied to other MABs. You might have heard of the work of Perron et al? They argue that endogenous retroviruses might be at the core of diseases so different as MS and schizophrenia, and they've got solid virology studies to back the claims up (prevalent in both syndromes). Lab mice even get sick when injected with the MS endogenous retrovirus, and they cope fine when they are given the MAB designed to target the retrovirus. Right now they have started human trials (phase II).

I think there are some clear indications that if a RV is behind ME it would also be endogenous - so, my thoughts are that if the Perron study bear fruits, chances are it would implications for ME as well.

I had to dig up the info about India and post marketing studies - and judging from this it looks like it's not common at all to such studies there. Why Spain if I'd do it again? They have good health system and it's used off-label at a clinic there. What made me feel that RTX would be relatively safe compared with other treatments, is that it's used widely on people with RA, and many of which do also have ME. So since it was safe for them, it was safe enough (as a long shot) for me.

 

[redo]

Hospital monitoring, or equivalent trained medical monitoring, is mandatory for this drug. An occasional patient has extreme reactions - in a hospital its easy to deal with, if you are far from quality care it could be life threatening.

I am hoping they can massively increase the rate of full recovery with this drug (no continuing treatment required). If so it will be easy to sell the idea to governments (and maybe insurance companies) that it should be subsidized. If not this will be a hard drug to convince anyone to subsidize.

Bye, Alex

The government in most countries with universal health care pays for RTX when given for RA - and the treatment has varying results when it comes to that condition too, so I guess chances are it could be offered for free for PWME as well, even if the phase III studies turn out like the previous study. My impression is that RTX treatment responses might be like with RA; some get better, others not, but if one thing doesn't help, other immune modulating/suppressing agents might work... I guess that's much of the reason Mella/Fluge are trying the other RA drug Enbrel on PWME right now.

 

[Sherlock]

What made me feel that RTX would be relatively safe compared with other treatments, is that it's used widely on people with RA, and many of which do also have ME. So since it was safe for them, it was safe enough (as a long shot) for me.

Thanks for all the welcome info, and for the cites - I will wend my way through them. To me, the RTX experiences are interesting because of the clues they provide. I'm thinking that CFS is like a Rube Goldberg machine - in some people, knocking out the B Cells brings it to a halt but that doesn't mean that's the only or best measure to take.

Btw, your downhill slide didn't result from the RTX, right?

Looking at your cite, "Safety Study of GNbAC1 in Multiple Sclerosis Patients", it seems as if that MAB binds right to a virus protein. Correct? Since ABs don't get through the BB Barrier, I'd wonder about that approach in M.E. - if there's indeed a virus in the brain or basal root ganglia or wherever. I know there are some rare MABs that get into the brain, but they are engineered to be endocytosed and then shuttled across the blood vessel cell, then exocytosed. Like so: http://www.nature.com/news/2011/110525/full/news.2011.319.html Very clever stuff.

 

[Sherlock]

Hospital monitoring, or equivalent trained medical monitoring, is mandatory for this drug. An occasional patient has extreme reactions - in a hospital its easy to deal with, if you are far from quality care it could be life threatening.

From my vantage point of seeing RTX used with lymphoma Pts (not me personally), the only ones who got RTX in-hospital were the ones who were already in there for other reasons.

If I were getting RTX, I think I'd rub my arm with a mouse well beforehand to see if I reacted.

A person can develop antibodies to the RTX. They would be classified as HACA - Human Anti Chymera Atibodies. That should result in lessened half life for the drug.

E.g.: http://rheumatology.oxfordjournals.org/content/44/11/1462.full
"Extremely high titer of anti-human chimeric antibody following re-treatment with rituximab in a patient with active systemic lupus erythematosus"

You'd think that might be a determining factor in response, but not necessarily: http://ard.bmj.com/content/69/2/409.abstract
"Clinical response, pharmacokinetics, development of human anti-chimaeric antibodies, and synovial tissue response to rituximab treatment in patients with rheumatoid arthritis"

 

[redo]

Thanks for all the welcome info, and for the cites - I will wend my way through them. To me, the RTX experiences are interesting because of the clues they provide. I'm thinking that CFS is like a Rube Goldberg machine - in some people, knocking out the B Cells brings it to a halt but that doesn't mean that's the only or best measure to take.

Btw, your downhill slide didn't result from the RTX, right?

Looking at your cite, "Safety Study of GNbAC1 in Multiple Sclerosis Patients", it seems as if that MAB binds right to a virus protein. Correct? Since ABs don't get through the BB Barrier, I'd wonder about that approach in M.E. - if there's indeed a virus in the brain or basal root ganglia or wherever. I know there are some rare MABs that get into the brain, but they are engineered to be endocytosed and then shuttled across the blood vessel cell, then exocytosed. Like so:http://www.nature.com/news/2011/110525/full/news.2011.319.html Very clever stuff.

Thank you too, for the info you bring to the table. I really appreciate it. I agree the clues for the pathogenesis of ME are highly valuable when it comes to RTX experiences. Also, if Enbrel (or another immunomodulating therapy) turns out to also have an effect, the search for common denominators can shed even more light on the cause of the syndrome. There are so many autoimmune conditions which responds to immune modulating drugs, but have an unknown cause, so my chips are on ME - in some years - being labeled as one of those.

My downhilld slide began after a ARV trial. The reactions following the ARV trial is another thing which leads me to believe a RNA virus is involved. Me and the other poster here at PR didn't use the same ARVs, but got the same aggravation of pretty much the same symptoms. And the symptoms which popped out aren't described in the side effects leaflet from either of the drugs.

It's been a while since I read the text. Yes, it's a protein suspected to cause havoc the MAB binds to, which is interrelated with the virus. Being healthy I used to be able to remember a page verbatim after I read it, and now the fog blurs out everything. It's sad.

The length of the stay when getting RTX varies slightly. Some require the patient to stay for a little longer, but mostly it's given polyclinically with a overnight stay at the hospital for the first infusion, and on the next many physicians let the patient go later the same day, so as your point is; the hospital stay isn't what costs.

Thanks for both the nature and bmj link. The risk of ARA and thereby resistance was actually one of things I thought about before going ahead, and it's nice to see that it seems to be safe with regards to that.

 

[Snow Leopard]

Is there any publically available safety data on the various biosimilar drugs? Reditux for example?

I've discovered that although all of these drugs target the same glycosylated phosphoprotein, when the drug is produced with a different method, it will necessarily be different in structure/phosphorylation and so this is why new safety trials have to be done to prove that the biosimilar drug is safe.

 

[Sherlock]

My impression is that RTX treatment responses might be like with RA; some get better, others not, but if one thing doesn't help, other immune modulating/suppressing agents might work... I guess that's much of the reason Mella/Fluge are trying the other RA drug Enbrel on PWME right now.

Now that is very interesting, Redo - etanercept is generating reports of fast responses in a wide variety of conditions, which is always interesting if you can reasonably believe that the fast effect is not just from the power of suggestion.

Thinking out loud:

One example of many video testimonials, this one in the setting of post stroke:
"Rapid improvement in chronic stroke deficits following perispinal etanercept"
www.youtube.com/watch?v=5uDOudjOshY @1:45
"...within ten minutes following the treatment..."

There's a Dr. Tobinick who seems to be the pioneer in using etanercept off label in novel applications. I suppose all of the testimonials are Pts of his practice - has also seems to have patented a spinal injection procedure.

A published Tobinick case study:
"Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration"
http://www.jneuroinflammation.com/content/5/1/2
(seems like a high impact factor article, FFT)

Yet here is a complaint that Amgen does not support research in novel uses, only independent researchers are doing so:
"Keynote: Repurposing of Enbrel® for Alzheimer"
www.youtube.com/watch?v=VvL9j9GRfds @3:36

It looks as if TNF blockers just maybe can have the potential to knock RTX out of the box for use in management of CFS one day. I see that etanercept is also being used for sciatica pain, so maybe it'd even work for M.E. pain, in some undefined population subset.

An India made version: http://www.tajdrug.com/Etanercept.htm

It's home injected subQ in many uses, btw. [edit: I wonder if some daring and/or desperate soul has ordered up a few prefilled syringes and took a shot at it.]

That's enough typing for now. I think I'm going to get some beakers and a hamster and mix some up. If I don't post again, then that probably means it didn't go so well

 

[Sherlock]

the manufacturer's doc from 2007, "Dr. Reddy’s launches Reditux™ – Monoclonal Antibody Treatment for Non-Hodgkin’s Lymphoma":

Reditux™ is approximately priced at half the originator’s price.

http://www.drreddys.com/products/popups/reditux.htm

the company stock is listed on the NYSE, so they're certainly far from little: Dr. Reddy's Laboratories (NYSE: RDY)

they also claim:

Dr Reddy’s also launched its social initiative called “Sparsh” - an Assistance Program for cancer patients undergoing treatment - at the Reditux™ launch. Patients identified by the doctors through Sparsh would be provided Reditux™ free of cost.

 

[Jacque]

Now that is very interesting, Redo - etanercept is generating reports of fast responses in a wide variety of conditions, which is always interesting if you can reasonably believe that the fast effect is not just from the power of suggestion.

Thinking out loud:

One example of many video testimonials, this one in the setting of post stroke:
"Rapid improvement in chronic stroke deficits following perispinal etanercept"
www.youtube.com/watch?v=5uDOudjOshY @1:45
"...within ten minutes following the treatment..."

There's a Dr. Tobinick who seems to be the pioneer in using etanercept off label in novel applications. I suppose all of the testimonials are Pts of his practice - has also seems to have patented a spinal injection procedure.

A published Tobinick case study:
"Rapid cognitive improvement in Alzheimer's disease following perispinal etanercept administration"
http://www.jneuroinflammation.com/content/5/1/2
(seems like a high impact factor article, FFT)

Yet here is a complaint that Amgen does not support research in novel uses, only independent researchers are doing so:
"Keynote: Repurposing of Enbrel® for Alzheimer"
www.youtube.com/watch?v=VvL9j9GRfds @3:36

It looks as if TNF blockers just maybe can have the potential to knock RTX out of the box for use in management of CFS one day. I see that etanercept is also being used for sciatica pain, so maybe it'd even work for M.E. pain, in some undefined population subset.

An India made version: http://www.tajdrug.com/Etanercept.htm

It's home injected subQ in many uses, btw. [edit: I wonder if some daring and/or desperate soul has ordered up a few prefilled syringes and took a shot at it.]

That's enough typing for now. I think I'm going to get some beakers and a hamster and mix some up. If I don't post again, then that probably means it didn't go so well

 

[Jacque]

Wow...quite interesting info... esp the Alz part...my Daddy is and has been dying with Alz for 6 looong years now... They call it the LONG GOODBYE for a very SAD reason... They have GOT to figure this out... I cannot remb where I read this but here was the Stat... By 2025 - 50% of peep over 50 will have Alzheimers... now is that frightening or WHAT? I know if something doesn't change drastically...I will be in that group...already feel half way there a lot of the time already... SOMETHING is eating the brain...and they better FIGURE IT OUT... But oooh nooo they are spending our Govt $$ putting a rover on MARS...when our country is literally going down the tube "health" wise.

Have you ever heard of the book LAB 257? Pretty damn scarey when it comes to Lyme and Bioterrorism... What a better way to make millions sick than BUGS..? The #1 killer of humans on this planet!!

Gonna watch those U tube videos tomorrow... Thx

So Sherlock why do you think that many of the men with ME do not have PAIN like we women seem to have???? I find that interesting? hmmmmmm

 

[Sherlock]

So Sherlock why do you think that many of the men with ME do not have PAIN like we women seem to have???? I find that interesting? hmmmmmm

I didn't know that, thanks. I don't know much about ME muscle pain because I've never really had any. I have had:

• times when my muscles didn't work right
• times of getting DOMs too easily

Maybe that's the same process as ME pain but I'm underneath some threshold, I don't know. Yes, Jaq, it is something to think over... in another thread

Why men get less pain, and less CFS/ME anyway? The knee jerk answer of testosterone seems to be not true, else we would have heard of great improvement by men or women taking T or anabolic steroids. Maybe it's from having not more T but less estrogen or progesterone?

 

[barbc56]

By 2025 - 50% of peep over 50 will have Alzheimers... now is that frightening or WHAT? I know if something doesn't change drastically...I will be in that group

Where did you get this number. It seems awfully high. Do you have the gene for Alzheimers as some forms are genetic.

Thanks.
Barb C.

 

[Sherlock]

Just for fun:

I enquired for Reditux pricing: ~$700 Yankee dollars for 500mg. Using Mella and Fluge dosing of 500mg/meters-squared, and going to a body surface calculator: http://www.halls.md/body-surface-area/bsa.htm

So let's say very roughly that = two vials, which = $1500 including special shipping.

Let's look at dosing regimen:
http://www.rxlist.com/rituxan-drug/indications-dosage.htm
http://www.drugs.com/dosage/rituximab.html

Note that lymphoma dosing is only 375mg/m2 which is less drug, since there presumably is more risk. Selecting the rate for rheumatoid arthritis (which happens to be 1000mg total and apparently not varying by body surface), we see it is given at 50mg/hr for the first thirty minutes, then escalated by 50mg/hr every half hour up to 400mg/hr - in the absence of any infusion reactions.

It's theoretically possible that in the distant future, people might self inject small doses over days (as with etanercept) and minimize infusion reactions. DON'T TRY THIS AT HOME But one difference is that RTX lyses cells and spills their contents, while etanercept merely grabs and holds onto a TNF molecule.

(As I have been reading, etanercept is a bona fide receptor of TNF, as appears on human cells. Attached to it's back end, so to speak, is the Fc region of IgG - the bottom end of the Y shape that is an antibody. So cells like neutrophils presumably can grab onto the Fc region, then swallow up in total the etanercept and it's catch (the TNF molecule) - like an imaginary whale swallowing a fish with a crab in its mouth, thereby ensuring that the crab can't do any harm.)

Half-life is only 70–132 hours for etanercept, as opposed to months for RTX.