Invest in ME/Prof Jonathan Edwards statement on UK Rituximab trial, 30 July

[Roy S]

Bravo! excellent news and written in a way that is a pleasure to read.

Time for another Hanlon article?
(appropriate emoticon not available)

Actually, I think Sonia Poulton is overdue for another article.

 

[Dolphin]

The patent issue is interesting.
I'm not sure of the details in this case.
But if a drug company has a patent, it is in their interest for the drug to be used and so in their interests to spend the money on trials.
[Aside: In the case of Ampligen, unfortunately the drug company is not big, but that won't be the case in other situations].

Some people who haven't been ill/diagnosed too long may think they can avoid drugs to get better (and some people indeed do seem to get better fairly quickly after some infections like Epstein Barr Virus). For people who are ill longer, the best hope I think is with drug therapy, which will sometimes involve drug companies who have patents.

 

[Firestormm]

Yes I must admit MeSci and Dolphin I hadn't considered the patent and drug company issue - or even thought of it as an issue. I guess it is one. Most important is to establish that Rituximab is a drug capable of treating ME. For me I would have preferred establishing why - but replication is a necessary part of the process. That the drug company (or it's shareholders) will also be a beneficiary is a necessary 'evil' I am afraid. Not a lot we can do about that. There was some talk about Rituximab coming off patent and the company not being interested in Trials for ME because of this - but I am confused and can't really remember if that was conjecture or fact. Has anyone actually approached the drug company? If replication is achieved - through whatever means/number of independent trials - then what's the next step for approval in the UK for treatment of ME? What other hoops are there - does anyone know? Thanks

 

[MeSci]

Yes I must admit MeSci and Dolphin I hadn't considered the patent and drug company issue - or even thought of it as an issue. I guess it is one. Most important is to establish that Rituximab is a drug capable of treating ME. For me I would have preferred establishing why - but replication is a necessary part of the process. That the drug company (or it's shareholders) will also be a beneficiary is a necessary 'evil' I am afraid. Not a lot we can do about that. There was some talk about Rituximab coming off patent and the company not being interested in Trials for ME because of this - but I am confused and can't really remember if that was conjecture or fact. Has anyone actually approached the drug company? If replication is achieved - through whatever means/number of independent trials - then what's the next step for approval in the UK for treatment of ME? What other hoops are there - does anyone know? Thanks

Patents are for specific uses of a drug. So if rituximab is 'repurposed' for ME, it can be repatented for that purpose. You can read a bit about this practice here:

http://cen.acs.org/articles/90/i40/Drug-Repurposing.html?h=-1031248274

notably "Anyone can patent a new use, dosage, or formulation."

 

[MeSci]

The patent issue is interesting.
I'm not sure of the details in this case.
But if a drug company has a patent, it is in their interest for the drug to be used and so in their interests to spend the money on trials.
[Aside: In the case of Ampligen, unfortunately the drug company is not big, but that won't be the case in other situations].

Some people who haven't been ill/diagnosed too long may think they can avoid drugs to get better (and some people indeed do seem to get better fairly quickly after some infections like Epstein Barr Virus). For people who are ill longer, the best hope I think is with drug therapy, which will sometimes involve drug companies who have patents.

I have to disagree here, Dolphin. I have had ME for 18 years, but have experienced significant improvement in the past year after going gluten-free and reducing sugar and grains, taking specific supplements and pacing more rigorously, following my reading of papers on leaky gut. I maintain hope that improvement will continue, and I have no wish to take a drug, least of all a dangerous one.

 

[Sasha]

Glad you've had such success with non-drug therapies, MeSci - but as with all these immune therapy drug trials we're trying to get (Ampligen, Rituximab, etc.), there are benefits to PWME beyond personal use of the drug. Even if you never use it, just having an immune therapy be shown to work in an RCT and confirmed will validate ME as an immune disease, which will have huge knock-on effects for how society views us, how we're treated, how much research funding our disease gets, and so on and on. As the science progresses, less dangerous drugs might come online for us.

 

[Dolphin]

The patent issue is interesting.
I'm not sure of the details in this case.
But if a drug company has a patent, it is in their interest for the drug to be used and so in their interests to spend the money on trials.
[Aside: In the case of Ampligen, unfortunately the drug company is not big, but that won't be the case in other situations].

Some people who haven't been ill/diagnosed too long may think they can avoid drugs to get better (and some people indeed do seem to get better fairly quickly after some infections like Epstein Barr Virus). For people who are ill longer, the best hope I think is with drug therapy, which will sometimes involve drug companies who have patents.

I have to disagree here, Dolphin. I have had ME for 18 years, but have experienced significant improvement in the past year after going gluten-free and reducing sugar and grains, taking specific supplements and pacing more rigorously, following my reading of papers on leaky gut. I maintain hope that improvement will continue

Just to clarify that when I said "get better", I meant to full or near full functioning e.g. able to work full-time.

I have tried management techniques and supplements that appeared to help me.

Also, I just said what I thought in my opinion was the best hope, not the only hope.

But people are free to disagree.

and I have no wish to take a drug, least of all a dangerous one.

That is where we differ (although I won't be rushing to take Rituximab myself).

 

[MeSci]

Just to clarify that when I said "get better", I meant to full or near full functioning e.g. able to work full-time.

I have tried management techniques and supplements that appeared to help me.

Also, I just said what I thought in my opinion was the best hope, not the only hope.

But people are free to disagree.

Of course!

BTW I meant also to mention publication bias by pharmaceutical companies. There is an article about this here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2580079/

They have been found to have a tendency to over-publish studies that show their drugs in a good light and avoid publishing those that do not show good efficacy and/or safety.

No one yet has a patent for rituximab for ME, but clinical trials may pave the way for such a patent, and then any company obtaining a patent and licence in the EU for this purpose will have a monopoly on the drug for that purpose for 20 years, and make a lot of profit without having to spend much, this profit being partly thanks to trials funded by donations in this case.

 

[Sam Carter]

Of course!

BTW I meant also to mention publication bias by pharmaceutical companies. There is an article about this here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2580079/

They have been found to have a tendency to over-publish studies that show their drugs in a good light and avoid publishing those that do not show good efficacy and/or safety.

No one yet has a patent for rituximab for ME, but clinical trials may pave the way for such a patent, and then any company obtaining a patent and licence in the EU for this purpose will have a monopoly on the drug for that purpose for 20 years, and make a lot of profit without having to spend much, this profit being partly thanks to trials funded by donations in this case.

From a brief skim of Google's patent search it looks like Mella and Fluge might already have such a patent.

 

[Dolphin]

Of course!

BTW I meant also to mention publication bias by pharmaceutical companies. There is an article about this here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2580079/

They have been found to have a tendency to over-publish studies that show their drugs in a good light and avoid publishing those that do not show good efficacy and/or safety.

True.
Hopefully initiatives like All Trials will help with something like this.

However, we see in the ME/CFS domain that such problems can exist with non-pharmacological approaches e.g. the hyping of the efficacy/effectiveness of graded activity-oriented approaches (CBT, GET, etc.), the poor reporting of harms/safety measures
e.g.

Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
http://iacfsme.org/BULLETINFALL2011/Fall2011KindlonHarmsPaperABSTRACT/tabid/501/Default.aspx

I've read about similar problems with chiropractors, for example.

Also drugs are better regulated than non-pharmacological behavioural approaches or supplements so there can be greater risk of problems not being collated.

And the manufacturing of supplements isn't always well-regulated in terms of quality.
Also often one can't get them paid for by medical systems/insurance.

No one yet has a patent for rituximab for ME, but clinical trials may pave the way for such a patent, and then any company obtaining a patent and licence in the EU for this purpose will have a monopoly on the drug for that purpose for 20 years, and make a lot of profit without having to spend much, this profit being partly thanks to trials funded by donations in this case.

It is an interesting issue that hopefully will be looked at.

But again to point out that profits would only be made from a patent for Rituximab for ME or CFS if the drug is being used (in this case in the EU).

So if, for example, it was available on the NHS, as it is for other conditions, many patients might not be concerned if a drug company was making a profit - most patients' main concern would be to have access to the drug. Companies make profits out of all sorts of things in people's lives. And drug companies will only make a profit it is used.

 

[user9876]

Patents are for specific uses of a drug. So if rituximab is 'repurposed' for ME, it can be repatented for that purpose. You can read a bit about this practice here:

http://cen.acs.org/articles/90/i40/Drug-Repurposing.html?h=-1031248274

notably "Anyone can patent a new use, dosage, or formulation."

Fluge and Mella have filed a patent for using Rituximab for ME
http://www.google.com/patents/EP207...a=X&ei=4kT5UYHPFo3o8wSk9IDIBg&ved=0CEIQ6AEwAg

Interestingly the european application appears to have been withdrawn at least the europe (since 2010) It looks like they didn't want to pay further fees. The initial fees are quite cheap but as time goes on they ramp up. Once the idea is published you can't patent it (unless in the US in which case you have a year).

https://register.epo.org/application?number=EP08000006

 

[Bob]

A brief post by Charles Shepherd on MEA's Facebook page, re potential future MRC funding for a Rituximab study...

... it is incorrect to state that the MRC will not fund a Rituximab trial. The protocol has not yet been fully prepared and finalised. There is no reason why it cannot then be submitted to the MRC - possibly in the form of a study that could be jointly funded by the MRC and the charity sector. The MRC is very keen on this type of co-operation. Hence the decision by the MEA RRF to co-fund the muscle research study in Liverpool with the MRC.

https://www.facebook.com/permalink....comment_id=5248598&offset=0&total_comments=48

 

[Sasha]

Last day to donate to the trial and get it matched pound for pound - about £250 to go, I think (ignore the total on that page, that's their long-term total):

http://www.justgiving.com/onedayonepound

 

[Jonathan Edwards]

To avoid confusion it seems best to post further comments on the use of rituximab on this thread (even if my they got my name wrong!). This follows from something Bob said on the funding thread. I said that I thought rituximab was not as dangerous as a lot of people make out. I am on a steep learning curve for ME (I spent my career on rheumatoid arthritis) and am beginning to see comments on reactions to rituximab. I am interested in why this should be.

One simple factor is that we got reactions with the drug until we learned to look for early signs and to be very careful with the infusion delivery. There are now few reactions at the unit. Another point is that if the dose given is too small, reactions might occur with further doses. This sounds odd but this is a drug with a complicated action. A more important factor is that reactions may depend on what disease is being treated. I note that someone with CFS and a positive antinuclear antibody developed rituximab pneumonitis (can present as BOOP or ARDS). Pneumonitis is not properly documented with rituximab but it is the reaction that most concerns me. We saw more of it early on, for reasons I do not fully understand. It may be a particular risk in conditions with anti-nuclear antibodies - that is just a thought from some cases. If reactions are more frequent in ME/CFS then we need to think carefully about that.

Fluge and Mella did not report major problems but if we are to do further studies it would be very useful to know what reactions have occurred. Fifteen years ago I set up a worldwide database to try and pool results and reactions with use of rituximab in all autoimmune conditions. It fairly soon got overtaken by published reports but it was useful for a year or so. I am interested to know, outside the Norwegian study, just how many people have been treated for ME and what reactions may have occurred (and even who got better!). My email is jo.edwards@ucl.ac.uk .

In other words, I still think rituximab is safe to use for rheumatoid arthritis, but I have to be more cautious about predicting that for everyone with ME. If there really are more reactions maybe that is telling us something important about ME. (A strange thing about rituximab is that in full dose it probably blocks any usual sort of allergic reaction to itself.)

 

[Undisclosed]

Jonathan Edwards -- your name is now spelled correctly in the thread title.

 

[biophile]

This is not a criticism but I suspect many patients may share my own personal reluctance, even fear, against trialling trying Rituximab [for themselves], despite seeing the promising results and being desperate to improve, because of an acquired sensitivity to multiple medications, and also watching their health decline apparently due to other treatments which were supposed to be "safe". What happens to the vast majority of people suddenly doesn't mean jack when you're the one who cops the rare adverse effects. Life is about taking reasonable risks, but I also want to safe guard what limited function I have left.

 

[Dolphin]

This is not a criticism but I suspect many patients may share my own personal reluctance, even fear, against trialling Rituximab, despite seeing the promising results and being desperate to improve, because of an acquired sensitivity to multiple medications, and also watching their health decline apparently due to other treatments which were supposed to be "safe". What happens to the vast majority of people suddenly doesn't mean jack when you're the one who cops the rare adverse effects. Life is about taking reasonable risks, but I also want to safe guard what limited function I have left.

I certainly understand this viewpoint.

However, I would be very unhappy if trials were blocked for ethical reasons because of a fear of side effects. This illness can lead to long-term complications from immobility, weight gain (while not universal, there is increased risk of it from a decrease in activity levels and, for some people, medication), inflammation, etc, possibly shortening lives. And it certain has a major effect on morbidity.

Current treatments such as exercise programmes are certainly not without their risks either.

So while I don't think anyone should be forced to take the therapy (and I can't see that being an issue in my lifetime), I think the facility should be there to trial the drug.

 

[Bob]

This is not a criticism but I suspect many patients may share my own personal reluctance, even fear, against trialling Rituximab*, despite seeing the promising results and being desperate to improve, because of an acquired sensitivity to multiple medications, and also watching their health decline apparently due to other treatments which were supposed to be "safe". What happens to the vast majority of people suddenly doesn't mean jack when you're the one who cops the rare adverse effects. Life is about taking reasonable risks, but I also want to safe guard what limited function I have left.

* [edit: Trying it for myself I mean].

I totally understand your worries here, but that's the whole point of medical trials. They test the safety and efficacy of the treatment, in a very controlled environment. Profs Fluge and Mella haven't reported experiencing any major safety problems, as far as I am aware. If there are no serious adverse effects in larger trials, then we can move forwards cautiously.

I can't remember the exact details about this, and I haven't read any actual research evidence, but I've read that the most severest of reactions are seen in cancer patients, and this is because of the interaction between Rituximab and other cancer treatments. Again, I've not seen any actual research evidence for this, but I think it's worth keeping in mind.

 

[ukxmrv]

I have to disagree here, Dolphin. I have had ME for 18 years, but have experienced significant improvement in the past year after going gluten-free and reducing sugar and grains, taking specific supplements and pacing more rigorously, following my reading of papers on leaky gut. I maintain hope that improvement will continue, and I have no wish to take a drug, least of all a dangerous one.

You could have done that all 18 years ago though , MeSci. Those of us who did that and had no improvement are the ones who will be volunteering for the drug trials. There needs to be options available for all groups.

 

[biophile]

I probably should not have used the phrase "trialling Rituximab" when I meant trying it for ourselves. I do not have a problem with actual research into it, I even donated recently to the Invest in ME initiative. I just wanted to point out why some patients may be reluctant to try it for themselves even if it supposed to be effective and safe.

They test the safety and efficacy of the treatment, in a very controlled environment. Profs Fluge and Mella haven't reported experiencing any major safety problems, as far as I am aware. If there are no serious adverse effects in larger trials, then we can move forwards cautiously.

The exact same thing has been said about CBT/GET, which is supposed to be effective and safe too. I have spent enough time and energy evaluating the evidence for CBT/GET to know this is questionable, and I have bad life experiences with GET. I have little reason to doubt whatever limited evidence there is for Rituximab so far, but my concern is not just about "severe reactions" but ANY significant decline in health whatsoever which would make life not worth living anymore.

Years ago I had intravenous EDTA chelation therapy, which was probably quackery but is still supposed to be relatively benign. I have made many cumulative mistakes, but that treatment happened to coincide with the beginning of a rather dark phase for my health, and maybe this is irrational enough to require CBT (hehe), but considering that I cannot even tolerate a daily aspirin anymore without a decline in health, the thought of infusing something like Rituximab scares me.