New Rituximab ME/CFS open-label phase II study with rituximab maintenance treatment

[medfeb]

I heard that because of the patent expiration, it would not pay for them to invest money in trials. Is it possible to extend a patent?

Yea, you are right - I've heard that also but forgot when I asked the question. I do not know what all the rules are on extending patients but think it can include new dosage forms and new indications.

But my more generic question is to what extent does the Rituxan success make it easier to start attracting any drug development company.

 

[leokitten]

Not particularly. My guess is that approximately a third of the people currently diagnosed with ME/CFS, even under the best definitions we have, have a different illness than the other two thirds. In both cases the illness is very serious. The symptoms are similar, possibly because of secondary effects (inflammation, cytokines, neurological impacts), but the root of the illnesses may be different.

For example (not saying I think this IS the case, just pointing out how it COULD happen), if chronic EBV were the root cause for 2/3 of ME/CFS patients, antivirals and B-cell depletion might help them, while if Lyme was at the root of the other 1/3 of cases, those treatments might not help, but the right antibiotic treatment might. I'm sure the real situation is a great deal more complex, but the point is that the 67%/33% pattern we're seeing could simply be an indicator of subsets (or distinct conditions).

I believe most of the 1/3 non-responders do actually have the same underlying disease and they don't respond to Rituximab because of differences in depletion of particular B-cell subsets. Long story short rituximab doesn't knock out the right B-cells for long enough in these people. Fluge/Mella mention investigating this theory in the Discussion and I believe there will be a discovery on this front in the future.

 

[Kati]

I believe most of the 1/3 non-responders do actually have the same underlying disease and they don't respond to Rituximab because of differences in depletion of particular B-cell subsets. Long story short rituximab doesn't knock out the right B-cells for long enough in these people. Fluge/Mella mention investigating this theory in the Discussion and I believe there will be a discovery on this front in the future.

Hi @leokitten Rituximab knocks out all b-cells, actually, but perhaps it could be that another group of cells need to be knocked out as well, so I partially agree with you.

If we have a pathogen, it maybe that on top of affecting the B-cells, the pathogen also lives somewhere else, say, bone marrow, or brain.

It certainly sucks to be a non-responder

 

[ahmo]

Regarding India: Ikgdar is Roche's Rituximab version in India

I checked the site I use for naltrexone. It's not listed, but shows a standard response to contact them to look into it. http://www.alldaychemist.com/contacts

 

[Misfit Toy]

I'm not following. Which group are you saying are the AH,EV, and PV

Those with signs of active herpes, enterovirus, and parvovirus infection and/or hypogammaglobulinemia, i.e. some portion of ME patients.

MISFIT TOY'S RESPONSE:
----------------------------------------------

That would be me. CVID. Hypogammaglobulinemia. Yup, me.

 

[msf]

Barb56, if they don't take Maes seriously, why do they refer to his recent findings in their paper? Gottfries is the one that found HSP60 epitopes that looked like Chlamydial ones in people with ME.

 

[msf]

SOC, it would be great if it were that simple, but I doubt it is...one of the patients in this study apparently developed ME after being infected with Borrelia, and they were one of the ones who got no benefit from the Ritux...however, this patient was also involved in one of the earlier Ritux studies, and in that one they did seem to respond! Since several people have talked about Chronic Lyme being partly an immunological disease, I don't think it would be too surprising if Rituximab had some effect on these patients.

 

[Sasha]

When you find a candidate, please make sure they are into polygamy - we can all go to Norway together!

Great plan! I'm in.

Simon and I now have an article up on the home page - big kudos to @Simon (probably still unconcious) who did the heavy, heavy lifting on this and analysed and wrote about a massive 54-page paper, and to @Mark and @Jody for making it possible to come out as quickly as it did (no mean feat for a whacking great paper like that, at short notice).

 

[Forbin]

I'm hoping (assuming actually) that they stored the patients' blood samples prior to the trial. It might be very interesting to see what happened to the responders' plasma cytokine levels, vis-a-vis the 2015 Columbia study, pre and post treatment.

 

[Sasha]

So I think we need to be persuading someone who could afford to fund a decent phase 3 clinical trial to do so here in the UK....sooner rather than later and certainly before late 2017/early 2018 when we will hopefully have the results of the phase 3 Norwegian trial that is now in progress.

And if we have the whole spectrum of medical opinion on board here, including the psychiatrists, then the prospect of setting up a phase 3 trial here in the UK does look far more encouraging.

If this doesn't happen, it could well be 2020 before people in the UK start to benefit from the first effective form of drug treatment aimed at the underlying disease process in ME/CFS,

Glad to see the MEA thinking strategically, Charles - I'd like to see all our charities and ME rituximab experts getting together and coming up with a strategy and some advocacy goals to get this happening, whether it's a move towards rituximab or cyclophosphamide.

I'd love to know what patients should be doing in terms of advocacy around this, in the UK.

It's a huge opportunity both for advocacy off the back of the findings (of the 'look, it's a real disease!' and 'donate, a cure is achievable!' variety), and for advocacy towards getting us rituximab or similar-acting treatments faster.

Itching to DO something!

Meanwhile, I hope people are exploiting the opportunity by hijacking the media.

 

[deleder2k]

Does anyone in Norway want to marry me?

Send your pictures and CV in my inbox and I will consider it

You could get one of these (+ me of course): http://www.dailymail.co.uk/travel/t...n-complete-secret-images-Northern-Lights.html

 

[deleder2k]

I checked the site I use for naltrexone. It's not listed, but shows a standard response to contact them to look into it. http://www.alldaychemist.com/contacts

Ikgdar is the believed to be the exact same product as Mabthera/Rituxan. They changed the name of the product so that it would be illegal for most of the Western World to import it. One would probably have to go to India and get it. It was done by Roche to be able to compete with other biosimilars in India that were priced much lower than Mabthera (the real Rituximab).

I wonder if anyone will try out the new subcut version of Rituximab. It takes 5 minutes to inject. It is very convenient. It requires one to have one infusion without side effects. Then one can get the subcut version.

 

[Valentijn]

And in a similar way to Orwell's 1984 it will soon become hard for people to be sure of the truth regarding what really happened; what individuals actually said and did.

In the digital age, it's almost impossible to erase or bury the past, especially when it's been published. And until Wessely & Company apologize for and retract all of the baseless and horribly spun bullshit they've published, they're still very much on the hook.

The things which they did wrong were not specific to ME, but were deliberately abusive of the scientific process itself - saying "this proves patients should be taken seriously" does not suddenly make them better researchers, scientists, or human beings. It makes them opportunistic parasites who have been forced to abandon gnawing on one mangled body and now have to go look for a new victim.

The "better" Wessely excerpts are at http://forums.phoenixrising.me/index.php?threads/simon-wessely-quotes.21025/ and include such outrageous gems as:

• Forbidding patients to see specialists or doctors unless the CBT therapist agrees
• Minimizing referrals and limiting biological investigations
• Avoiding the use of medications to manage symptoms
• Advocating that patients be required to undergo CBT before being given sickness benefits
• Suggesting that carers perpetuate disability
• Stating that receiving benefits makes patients worse
• Insisting that patients should not be told to rest
• Passing the responsibility of rehabilitation to the patient
• Convincing doctors to deceive their patients
• Teaching that symptoms should be ignored in planning activity
• Conflating CFS with tiredness, fatigue, neurasthenia, burnout, various psychiatric disorders, and a cultural phenomenon

And that's without getting into his statements about symptoms and illness being perpetuated entirely due to psychological and behavioral factors, etc etc. He's said dozens of horrible things during his career, each of which is deserving of considerable outrage. Not because he was wrong about the disease, but because of the abusive ways in which he suggested that patients should be (un)treated, handled, and perceived.

 

[Sean]

saying "this proves patients should be taken seriously" does suddenly make them better researchers, scientists, or human beings.

Presumably that should be

"...does not suddenly make them..."

 

[deleder2k]

Not sure if this has been posted here: http://www.newscientist.com/article...gh-offers-hope-for-millions.html#.VZT1OxOqrXI

 

[Snow Leopard]

But my more generic question is to what extent does the Rituxan success make it easier to start attracting any drug development company.

It might attract others who have developed anti cd-20 monoclonal antibodies, but not much else. Other drug companies won't climb on board until we have already paved the road with gold. Ah I mean, found a highly specific biomarker.

 

[Sidereal]

Asinine comments by SW. You can already sense the beginnings of a sneaky shift happening, as so often happens in the academia, where the people who were your biggest critics and calling your theory crazy bullshit start saying things like "oh, we've been saying this all along" when the evidence for your position starts to become overwhelming. We must not allow them to get away with this.

Thankfully, unlike humans, the internet has a really long and accurate memory so his brand of pernicious quackery which has harmed millions and limited their access to healthcare, social services and societal legitimacy will never be forgotten. His writings are a matter of public record.

The only substantive contributions SW and his colleagues have made to the field of ME/CFS is that it is impossible to get funding for studies of biological mechanisms of disease and that visiting the emergency room or a doctor's office with a diagnosis of "CFS" on your chart is the equivalent of having the scarlet letter branded on your forehead, resulting in life-threatening neglect and abuse. My dog gets infinitely better treatment at her doctor's office than I do.

 

[charles shepherd]

Glad to see the MEA thinking strategically, Charles - I'd like to see all our charities and ME rituximab experts getting together and coming up with a strategy and some advocacy goals to get this happening, whether it's a move towards rituximab or cyclophosphamide.

I'd love to know what patients should be doing in terms of advocacy around this, in the UK.

It's a huge opportunity both for advocacy off the back of the findings (of the 'look, it's a real disease!' and 'donate, a cure is achievable!' variety), and for advocacy towards getting us rituximab or similar-acting treatments faster.

Itching to DO something!

Meanwhile, I hope people are exploiting the opportunity by hijacking the media.

We have a meeting of the Board of the UK Research Collaborative next Tuesday at the MRC in London - so I will certainly raise this at the meeting

As noted in the MEA statement, there will be a presentation on Rituximab from Dr Mella at the Research Collaborative conference in October in Newcastle during our Clinical Trials session

So yes, I fully agree that we need to get people in high places looking at the possibility of setting up a phase 3 trial here in the UK sooner rather than later…

I have, incidentally, just written to Andy C at the New Scientist to ask him to remove the link to Mental Health Topics in his coverage of Rituximab and ME/CFS:


Morning Andy

You will not be surprised to learn that there is quite a lot of comment appearing on the social media following your item on Rituximab. Eg:

http://forums.phoenixrising.me/inde...y-with-rituximab-maintenance-treatment.38477/

In relation to the pre-heading for the New Scientist item:

Antibody wipeout found to relieve chronic fatigue syndrome

• 19:00 01 July 2015 by Andy Coghlan
• For similar stories, visit the Mental Health Topic Guide

Please could you arrange for the link to the Mental Health Topic Guide to be removed asop and changed to a different part of the health section on the NS website

As you probably know, ME/CFS is classified as a neurological disorder by WHO in ICD10.

This WHO classification is fully accepted by the UK Dept of Health.

And the recent IoM and NIH reports from America both made it clear that ME/CFS is a complex multisystem disorder that should no longer be regarded as a mental health/psychological condition.

As you didn't manage to fit in my comments I have put them up on the MEA website anyway!

Regards

Charles

 

[Jonathan Edwards]

@Jonathan Edwards, would you care to comment on this? Do you know why they decreased maintenance dose?

And I'd also like you to comment on the study. I don't know if you've read the study earlier - but what was your first impression of the study?

It is easy to get these doses confused because it is easy to miss the per metre squared bit but it does look as if in phase 3 they are using 500mg maintenance. That seems very reasonable to me. I used that dose for pre-emptive maintenance of B cell depletion when I was investigating that. I am pretty sure that 500mg is plenty if given every 3 months.

The cost of rituximab in RA in the UK is about US$6,000 for the induction and 500mg maintenance should be US$1500 for the drug. Maybe add $2000 per infusion for infusion cost to that. My impression is that in the US people are being seriously ripped off but there may be other factors involved (like medical indemnity which is huge).

I have not read the paper yet as I am involved in other things this week but I will comment in due course.

 

[msf]

I don't really get why there needs to be a phase 3 study done in the UK, unless of course it's because of the general fear of foreigners that seems quite prevalent in the medical community in the UK. The only argument I can see for it is that they want to make sure that the Norwegian patients in the study are representative of ME patients in the UK, but then surely ever country with ME patients should then do such a study?