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Is Anyone Else Scared of Rituxan?

Bob

Senior Member
Messages
16,455
Location
England (south coast)
As far as I'm concerned, this seems more like trying to "fit a square peg in a round hole" in order to find a new target group to become consumers of a very expensive drug.
I think the patent for Rituximab has expired, hasn't it? This isn't an industry-led research program. The reason why Fluge and Mella are carrying out this research is because they witnessed their patients responding to the treatment. I think it's as simple as that.
 
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Bob

Senior Member
Messages
16,455
Location
England (south coast)
If ME patients have high viral titres (e.g. for herpes viruses), or any secondary infections, these issues may potentially be secondary to immune dysregulation (i.e. caused by immune dysregulation rather than the cause of immune dysregulation). The immune dysregulation may potentially be caused by B cell dysfunction or autoimmunity. If this were the case (i.e. high viral titres are caused by autoimmunity), then treatment with rituximab may potentially resolve these infections (secondary immunological issues), rather than allowing any infections to flourish.

There are lots questions at the moment. And there are subsets in ME/CFS. Time will give us more answers.
 
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deleder2k

Senior Member
Messages
1,129
I think the patent for Rituximab had expired, hasn't it? This isn't an industry-led research program. The reason why Fluge and Mella are carrying out this research is because they witnessed their patients responding to the treatment. I think it's as simple as that.


Expired in 2013 in Europe. It was set to expire in the US in 2016, but they managed to get it running to 2018.

Roche is not the only one going to produce Rituximab in the coming years:

Rituxan / MabThera (rituximab)
Drug developers:

  • Amgen: Biosimilar in development, with pivotal trial launched in 2013, the company stated in a letter to shareholders accompanying its Form 10-K for last year. The biosimilar is one of four for oncology indications that Amgen is developing in collaboration with Actavis.
  • Biocad: AcellBia registered in Russia; first monoclonal antibody biosimilar to receive a positive opinion from regulators. Agreement signed last year for export of rituximab APIs produced by Biocad and Kocak Farma
  • BioXpress Therapeutics: Biosimilar in pipeline
  • Boehringer Ingelheim: BI695500 in three trials recruiting patients as of April 30, according to ClinicalTrials.gov: A Phase III study assessing efficacy, pharmacokinetics, and safety of the biosimilar in patients with rheumatoid arthritis (NCT01682512); a Phase III study assessing the safety and efficacy of the biosimilar in patients with moderately to severely active rheumatoid arthritis (NCT01955733); and a Phase I study assessing the pharmacokinetics and pharmacodynamics of BI 695500 vs. rituximab as first-line treatment in patients with low-tumor-burden lymphoma (NCT01950273)
  • Celltrion and Hospira: Conducting Phase I trial in South Korea of CT-P10 for RA and another Phase I trial for lymphoma.
  • Dr. Reddy’s Laboratory: Reditux marketed in Bolivia, Chile, India, and Peru
  • iBio: Biosimilar in Phase I development. Company says its iBioLaunch platform, a gene expression technology that causes nontransgenic plants to rapidly produce high levels of target proteins, addresses several multibillion dollar markets including “biosimilars/bio-betters.” Announced October 5, 2011 that it produces rituximab in nontransgenic green plants.
  • Intas Biopharmaceuticals: MabTas marketed in India following launch February 26, 2013
  • Merck: MK-8808 the subject of U.S. clinical trials NCT01390441 and NCT01370694, both of which are active but not recruiting as of April 16 and May 1, respectively, the company disclosed on ClinicalTrials.gov
  • Oncobiologics and Viropro: Biosimilar in development; one of six monoclonal antibody biosimilars on which the companies agreed to collaborate under an agreement announced February 25, 2013. Viropro has rights to manufacture the six products being developed by Oncobiologics, with Viropro holding exclusive commercialization rights to the six for Malaysia, while both companies will co-manage Viropro’s Penang, Malaysia Alpha Biologics biomanufacturing subsidiary.
  • Pfizer: PF-05280586 in Phase I development for rheumatoid arthritis, the company confirmed in its May 8, 2014, pipeline update. Two trials ongoing but not recruiting participants, REFLECTIONS B327-01, a Phase I/II pharmacokinetic/pharmacodynamic study which compares the biosimilar to rituxumab in subjects with active rheumatoid arthritis with an inadequate response To TNF inhibitors (NCT01526057); and -06, an extension trial for patients who have participated in other PF-05280586 trials (NCT01643928)
  • Probiomed: Kikuzubam marketed in Bolivia, Chile, Mexico, and Peru
  • Roche: CEO Severin Schwan was quoted in March 2013 as pushing back his company’s anticipated launch of a rituximab biosimilar beyond the 2016 date he had earlier cited in The Wall Street Journal, until the end of this decade.
  • Samsung Biologics: Venture between Samsung and Quintiles halts development of SAIT101, in October 2012, reportedly due to uncertainty over biosimilar regulation in the U.S.
  • Sandoz: GP2013 in two clinical trials now recruiting patients: Phase III ASSIST_FL study assessing biosimilar in treatment of patients with previously untreated Advanced Stage Follicular Lymphoma (NCT01419665), the company told ClinicalTrials.gov on April 10, 2014; and a Phase I study in Japanese patients with CD20-positive low tumor burden indolent B-cell non-Hodgkin’s lymphoma (NCT01933516), according to the trial’s most recent update on August 28, 2013
  • Stada Arzneimittel: Joined with Gedeon Richter in announcing plans August 2011 to collaborate on biosimilars for rituximab and trastuzumab. Stada receives nonexclusive rights to sell Richter-produced rituximab in Europe and the Commonwealth of Independent States, excluding Russia. In addition to an undisclosed payment to Richter, Stada also agrees to pay Richter based on progress of the development of rituximab to a “low double-digit million Euros”
  • Teva and Lonza: On July 25, 2013, announce they will end four-year-old joint venture to develop, manufacture, and market biosimilar drugs, more than three months after Lonza issues a statement denying it will end the joint venture in response to its CEO, Richard Ridinger, telling the Swiss newspaper Finanz und Wirtschaft it was reviewing whether to continue the effort.
  • Zenotech Laboratories: Biosimilar marketed in India following launch February 27, 2013
Nature and indication: Chimeric mouse-human monoclonal antibody, for non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis

2013 sales: $8.998 billion [$7.898 billion (CHF 6.951 billion) Roche + $1.1 billion Biogen Idec], up 3.2% from 20126

Patent status: Patents expired November 2013 in EU, and set to expire 2018 in U.S.

SOURCE: http://www.genengnews.com/keywordsandtools/print/3/34899/ (Article is one year old)
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
This baffles me. Being one so skeptical against it I thought you had read something about what Rituximab is and what it really does. If you would then I guess your view on it would change.
Not sure what's so baffling. I've read some things about it but obviously there are still a few questions that I have.
 

DanME

Senior Member
Messages
289
With all due respect, right now there are many more people who have recovered (or as some might say, gone into remission) using other protocols (and usually multiple protocols over a period of years) than those who have recovered using RTX.

I know a half dozen from my own local support group who are back at work and have been since 2008-2009 (one is now retired). Several of them had milder cases, but as I've posted (to golf claps) a half dozen times before, one was sick for sixteen years, and the other was sick for 17 years.

During that 17 year period she was housebound for seven years, bedridden for 2 years (they later found mold in that apartment), and at one point her concentration was so poor she couldn't remember who she was talking to on the phone the second they stopped speaking. Yet she recovered completely, went back to school at agee 43 and has been well since 2009.

Some of them used some drugs from time to time like antibiotics, antifungals, antiparasiticals, but I can't think of a single one that didn't also use multiple forms of nutritional support, whether it was vitamins, minerals, amino acids, herbs, different types of probiotics (often rotated daily), not to mention dietary (including food intolerances and allergies) and 'lifestyle' changes. In hindsight it seems like overall the main focus was on natural remedies to rebuild the body, get the lymph flowing properly, restore gut function and detoxify pollutants, mold, and heavy metals.

There are people on this forum who have also recovered or gotten to 80% remission and have gone on with their lives. They're not here anymore because they have their lives back. Others have improved to a lesser but still substantial degree, but many of those were at their wits end when they thought nothing would save them except antiretrovirals a few years ago.

I understand why most patients can't see going this more 'natural' route, as it is very complicated and complex, and requires a lot of testing and a lot of $$$ and help in order to turn things around. Many of us have no income and are on medicaid or medicare so there's only so much we can do.

But that doesn't mean these things haven't worked for other people, no matter how 'woo' they may seem to some.

I am happy for everybody, who gets better, recovers or has gone into remission!

The problem with all your examples is, that they haven't been tested in a randomised controlled and blinded trial against a placebo treatment. While anecdotal evidence is not worthless (like the observation of Fluge and Mella that some people got better during chemotherapy), it is the weakest evidence, you can get in science. We cannot be sure, if people really got better, because of their treatment, or because of the placebo effect. Which includes everything from wishful thinking to the regression to the mean to spontaneous remission. Which could occur, especially in mild cases. In a lot of patients ME symptoms fluctuate a lot. So was it really the vitamins or the mold or not? We simply don't know.

The first phase II study in Norway was small, but properly conducted (though they had to move their end point). But the Norwegians didn't stop. They went on. Conducted a second open phase II study with similar results and are currently conducting a much larger study with definite endpoints to be sure once and for all.

What is the natural route? We have just hundreds of anecdotal stories, which haven't been tested in a RCT trial.
 

JPV

ɹǝqɯǝɯ ɹoıuǝs
Messages
858
The problem with all your examples is, that they haven't been tested in a randomised controlled and blinded trial against a placebo treatment. While anecdotal evidence is not worthless (like the observation of Fluge and Mella that some people got better during chemotherapy), it is the weakest evidence, you can get in science.
People put way too much faith in double blind studies...
Drug Companies & Doctors: A Story of Corruption (The New York Review of Books)

Many drugs that are assumed to be effective are probably little better than placebos, but there is no way to know because negative results are hidden. One clue was provided six years ago by four researchers who, using the Freedom of Information Act, obtained FDA reviews of every placebo-controlled clinical trial submitted for initial approval of the six most widely used antidepressant drugs approved between 1987 and 1999—Prozac, Paxil, Zoloft, Celexa, Serzone, and Effexor. They found that on average, placebos were 80 percent as effective as the drugs. The difference between drug and placebo was so small that it was unlikely to be of any clinical significance. The results were much the same for all six drugs: all were equally ineffective. But because favorable results were published and unfavorable results buried (in this case, within the FDA), the public and the medical profession believed these drugs were potent antidepressants.

In view of this control and the conflicts of interest that permeate the enterprise, it is not surprising that industry-sponsored trials published in medical journals consistently favor sponsors’ drugs—largely because negative results are not published, positive results are repeatedly published in slightly different forms, and a positive spin is put on even negative results. A review of seventy-four clinical trials of antidepressants, for example, found that thirty-seven of thirty-eight positive studies were published. But of the thirty-six negative studies, thirty-three were either not published or published in a form that conveyed a positive outcome. It is not unusual for a published paper to shift the focus from the drug’s intended effect to a secondary effect that seems more favorable.
I'd rather take anecdotal evidence, from a forum like this, over falsified information published by a corrupt pharmaceutical industry... any day of the week.
 

dannybex

Senior Member
Messages
3,561
Location
Seattle
I am happy for everybody, who gets better, recovers or has gone into remission!

The problem with all your examples is, that they haven't been tested in a randomised controlled and blinded trial against a placebo treatment. While anecdotal evidence is not worthless (like the observation of Fluge and Mella that some people got better during chemotherapy), it is the weakest evidence, you can get in science. We cannot be sure, if people really got better, because of their treatment, or because of the placebo effect.

Many of these things have indeed been tested in controlled trials, perhaps not specifically for ME, but for say specific symptoms like neurological problems (B12, folate), intestinal permeability (zinc-carnosine and specific strains of probiotics), or antifungals for fungal or mycotoxin infections in ME/CFS patients.

Perhaps you cannot be sure, but I can be, especially as I knew the persons involved prior to and after recovery/remission. And although I mentioned some who I haven't met in person, I've been in contact with them and have known them since at least 2006 (over on ProHealth), so I knew them at their very worst, knew the many things they tried, the things that made them worse and better. To suggest their improvement was based on the placebo effect is insulting, although I'm sure you didn't mean it that way.

Which includes everything from wishful thinking to the regression to the mean to spontaneous remission. Which could occur, especially in mild cases. In a lot of patients ME symptoms fluctuate a lot. So was it really the vitamins or the mold or not? We simply don't know.

You don't perhaps, but they do. Especially those who have ME/CFS-related mold/mycotoxin issues.

What is the natural route? We have just hundreds of anecdotal stories, which haven't been tested in a RCT trial.

People get ME/CFS from a variety of causes, so naturally (pun intended) there will be dozens iof 'routes' involved in their recoveries, as I noted in my original post. No one took one remedy and recovered, just like there will be no one drug for 'the cause' because there isn't one cause.

And you know as well as anyone, that there's a lot more money in drug development than there is in securing funds for studies using treatments that cannot be patented. Those studies went out the window for the most part in the mid-1980's just as the insurance companies and HMOs were taking over the health care system.

I'm not here to argue that anyone is right or wrong. Some will find benefits from drugs, others will not. Some will improve on a combination of allopathic and naturopathic treatments, while others may improve or recover by avoiding drugs completely. Everyone's different.

I just don't think it's fair to dismiss others recoveries/remissions by suggesting that they aren't as real or legitimate because they're "just" anecdotal, or worse, due to "wishful thinking".

Anyway, best of luck with your approach. It will be interesting to see how the final RTX studies come out.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
People put way too much faith in double blind studies...



I'd rather take anecdotal evidence, from a forum like this, over falsified information published by a corrupt pharmaceutical industry... any day of the week.

While this may be an legitimate issue in some cases, its obviously not an issue with regard to the studies being conducted at Haukeland university hospital. Fluge/Mella dont have the economical interest that bigger pharmaceutical often have, and there is now loads of evidence of patients going into actual remission.

Just saying, dont know if you were trying to hint otherwise though JPV :)
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
I just don't think it's fair to dismiss others recoveries/remissions by suggesting that they aren't as real or legitimate because they're "just" anecdotal, or worse, due to "wishful thinking".

The point is that without scientific studies, you cant know for sure that recoveries/remisssions are due to treatment X. Maybe the person using the treatment can be sure, but this is of no great use for the rest of the patient group. It is hard to get treatment from a doctor based on anecdotes. As already emphasized - ME does indeed for many have a fluctuating course, so if you take treatment X for a couple of months, and get better, well then you might just have gotten better all the same without the treatment.

I really do think it is very important to try out the treatments in studies.

And i would like to add - some people did indeed take one remedy and recovered - with Rituximab.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
I'm an still able to work full time with this disease but my life is complete hell, I have no life outside of work. Even though I'm not completely housebound/bed bound I would take rituximab because this is not living to me. I'm constantly in a state of PEM, crashing and managing my symptoms, I feel like I'm 100 years old and nothing in my body works right anymore.

I have been doing high dose Valcyte, Famvir, Doxycycline, Immunovir, LDN, other antibiotics and antifungals and a ton of supplements and have tried every god damn diet and lifestyle change that I could reasonably do without driving myself crazy. I take clonidine, gabitril, and gabapentin to fix my sleep issues.

Doing all of these protocols for over 1.5 years I haven't gotten better or recovered at all. Based on everything I've read from Fluge and Mella, that my symptoms seem very autoimmune and that I definitely have some kind of strange circulatory problems driving this disease from the moment I got ill, and the fact that aggressive antiinfective therapy has not worked I would try rituximab.

Rituximab is a lot less scary than for example anti-TNF therapy such as Humira and Enbrel. Supressing TNF alpha is dangerous yet people still take these drugs for autoimmune conditions.
 

deleder2k

Senior Member
Messages
1,129
Fluge and Mella stopped their study on anti-TNF drug Enbrel because of side-effects. From what I've heard RTX is safer than TNF-inhibitors.

@leokitten Could you work less so that you can actually enjoy your life? Is that an option? What about 50% disability or something? Everyone should have a chance to be with friends every now and then, and everyone should be able to take a holiday now and then. If the only thing you are able to do is work, then I would think about working less - if it is economically viable. Doing too much can also make one permanently worse with this disease, so it is careful to watch out for that! Best of luck.
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
Roche is not the only one going to produce Rituximab in the coming years:

Those competitors can't really be called Rituximab as they are merely biosimilars, and can potentially have a different safety and efficacy profile. (which means that they need to undergo their own clinical trials)

I'd rather take anecdotal evidence, from a forum like this, over falsified information published by a corrupt pharmaceutical industry... any day of the week.

I would in part agree, in that I'd consider all the evidence, to make sure it all agrees. But the key is that I have to know the person here as a regular member before they get better. That seems to remove much of the bias.
This is the same reason why I distrusted the XMRV testing results (forum results were much more negative) - because the pattern on this forum did not match what the scientists were saying.
 

deleder2k

Senior Member
Messages
1,129
What information would assure you of RTX, @Snow Leopard?

3 guys telling here that they've taken RTX. It worked for 2 of them. Last person didn't benefit.

Or:

A randomised, blinded trial with 30 patients with RTX conducted at a university hospital. 67% response rate for RTX, and 11% response rate in the placebo group.

I.e anecdotal evidence versus a scientific research with a placebo group.
 

Snow Leopard

Hibernating
Messages
5,902
Location
South Australia
What information would assure you of RTX, @Snow Leopard?

3 guys telling here that they've taken RTX. It worked for 2 of them. Last person didn't benefit.

Or:

A randomised, blinded trial with 30 patients with RTX conducted at a university hospital. 67% response rate for RTX, and 11% response rate in the placebo group.

I.e anecdotal evidence versus a scientific research with a placebo group.

Neither. Or at least not enough to make me want to hand over $10-15k of my own money (which would mean a loan etc).
 

Misfit Toy

Senior Member
Messages
4,178
Location
USA
@deleder2k -my question is...why do you seem to need people to want to take this medicine? I don't get it. It's great that you are for it, but why does everyone else have to be?
 

deleder2k

Senior Member
Messages
1,129
@deleder2k -my question is...why do you seem to need people to want to take this medicine? I don't get it. It's great that you are for it, but why does everyone else have to be?


I don't want anyone to take RTX before phase 3 is completed, and not before the FDA/EMA approves it. I am just trying to balance the view about this drug. It seems that some have decided already not to ever take it because they see some random web page list up side effects that sound scary. People have every right to be skeptical about it, and for many patients it won't be the solution. My goal is that everyone makes informed decisions about this drug from people that have worked with the drugs for years, especially @Jonathan Edwards, or from large studies conducted - not from unreliable web pages without references for their claims.

The reason I am positive about it is because it is our greatest hope in terms of treatment for PWME - ever. No randomised trial for any drug have provided the same results. We are still years before we know if this will be a solution for a sub group of PWME. And until the phase 3 study is completed we won't know if this is a viable medicine for us.

According to Twitter the open phase 2 study will be published in 2-3 weeks. That will be very interesting. I will certainly read it, and I urge everyone to do the same.
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
@leokitten Could you work less so that you can actually enjoy your life? Is that an option? What about 50% disability or something? Everyone should have a chance to be with friends every now and then, and everyone should be able to take a holiday now and then. If the only thing you are able to do is work, then I would think about working less - if it is economically viable. Doing too much can also make one permanently worse with this disease, so it is careful to watch out for that! Best of luck.

Unfortunately I live in the U.S., there is almost not social safety net here like in Europe. I have no family or anyone to fall back on as well so have to work to have medical insurance and meet financial obligations such as a home and food. I am a scientist at the NIH and here in the U.S. in white collar jobs there really isn't anything like part time like you commonly see positions for in Europe (ie 50%, 80% positions). I lived in Europe for many many years where I went to grad school and worked for Novartis after. America is a much more ruthless and unforgiving place compared to Western Europe, especially if you have a disease like ME/CFS which the medical establishment and insurance don't believe exists and there's a lot of social stigma associated with it.

I don't ever want to go on disability or quit working because it would be difficult in my career to come back from that. Honestly I cannot wait until the RituxME trial is complete so that I can try it. I feel like I'm stuck in a prison that I cannot get better and I just want my life back so that I am not just working and crashing and recovering and working in a vicious cycle for the last 2.5 years.
 

deleder2k

Senior Member
Messages
1,129
I understand you. I guess I am lucky I was born in a country with a working welfare system

Maybe a bit off-topic: but have you tried IVIG or gammaglobulin subcut/IM?
 

leokitten

Senior Member
Messages
1,542
Location
U.S.
I understand you. I guess I am lucky I was born in a country with a working welfare system

Maybe a bit off-topic: but have you tried IVIG or gammaglobulin subcut/IM?

It is so expensive and not covered by insurance unless you have proven hypogammaglobunemia, which I don't have. My IgG levels and subclasses have always been good, yet my immune system is constantly having trouble controlling intracellular pathogens, in my case very high antibodies to EBV, CMV, HHV-6, M pneumoniae, and C pneumoniae.

I really don't think this is an infectious disease because i have been taking aggressive and targeted therapy against all these pathogens for over 1.5 years and I don't feel better. I have terrible circulatory problems like my body cannot control blood flow to parts of my body and I know for sure this is the root problem with me that this is causing all the other symptoms (fatigue, PEM, GI and genitourinary issues, cognitive dysfunction, muscle pain, etc).

I really think Fluge/Mella are on the right track and that many of us are in this subgroup with some kind of autoimmunity causing endothelial dysfunction resulting in poor blood flow to all our organs.

Right when I got sick I had a sudden and drastic tissue loss in those first 6 months particularly from my extremities, my shoe size went from 11 to 9, my hair started falling out like crazy and changed texture to become thin and unhealthy looking, it started going grey very quickly. I lost tissue basically everywhere and muscle even though I'm not deconditioned I move and walk around a lot and as I've said can still work full time.

ME/CFS never gave me OI or POTS it actually made my blood pressure and volume go up, I've had mutiple blood volume analyses via Daxor, my blood volume is way too high not low but I do not have any heart failure or kidney problems. My heart rate also became very low always in the low 50s which is what you would expect if your blood volume has gone too high.

Something is wrong with our vascular system this is the root cause for my subgroup.
 
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Snow Leopard

Hibernating
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5,902
Location
South Australia
What information would assure you of RTX,
A randomised, blinded trial with 30 patients with RTX conducted at a university hospital. 67% response rate for RTX, and 11% response rate in the placebo group.

I.e anecdotal evidence versus a scientific research with a placebo group.

Actually... Let's just say that you are one of the ones who received the active drug, but did not respond, or had severe side effects, how would you feel with regards to recommending it to others?