Rituximab Discussion

[Esther12]

The Norwegian trial has money but is still short ten million dollars last I read.

Ouch. I can understand funders being hesitant to put that sort of money up. Maybe we need a couple more smaller trials at different centres first?

 

[Bob]

From another thread, it seems that lots of research is ongoing, and that maybe they aren't ready to start the phase III trial yet. And the Norwegian government seems to be will to help:
http://forums.phoenixrising.me/index.php?threads/status-of-rituximab-me-cfs-studies.14655/

 

[Bob]

This is interesting:
http://niceguidelines.blogspot.co.uk/2011/10/study-demonstrates-that-95-of-mecfs.html

Discussed here:
http://forums.phoenixrising.me/index.php?threads/niceguidelineblog-study-points-95-pwcs-have-autoimmune-disease.12984/

 

[alex3619]

Another Maes paper identifies autoantibody differences and similarities in CFS and depression, and ties it to symptoms and oxidative but not nitrosative stress.

http://forums.phoenixrising.me/inde...utoantibodies-in-me-cfs-and-depression.18049/

Bye, Alex

PS Correction after reading full paper, nitrosative and oxidative stress are tied to different symptoms. Both are involved however.

 

[Ember]

The good news is that Rituximab comes to the end of its patent in about a years time, if I remember correctly, so there should be cheaper generic versions available.

I believe that the expiration date on the patent varies by country.

 

[Bob]

Doh! I should try reading the published paper before I start trying to understand what's going on!

The delayed response was up to 7 months.

Conclusion
The delayed responses starting from 2–7 months after Rituximab treatment, in spite of rapid B-cell depletion, suggests that CFS is an autoimmune disease and may be consistent with the gradual elimination of autoantibodies preceding clinical responses. The present findings will impact future research efforts in CFS.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026358

 

[Bob]

Interesting extract from the discussion section:

The B-cells have multiple immune functions, the main ones being antibody production, antigen presentation and regulation of the function and activity of other immune cells, i.e. T-regulatory cells, NK cells and macrophages [16]. Thus, the total effects of B-cell depletion on the immune system are likely to be complex and time-dependent.

In Stiff Person Syndrome, which is a rare autoimmune disease in the central nervous system with autoantibodies targeting glutamic acid decarboxylase (GAD65), the humoral autoimmune response was shown to consist of a Rituximab-sensitive part rapidly cleared after treatment, and a Rituximab-resistant part from long-lived and persistent plasma cells acting as a reservoir for secretion of autoantibodies. This may be one mechanism for lack of effect from B-cell depletion therapy [17].

An alternative explanation for the observed clinical improvement from B-cell depletion could be elimination or reduction of B-lymphotrophic viruses such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV). A recent study [18] showed clinical benefit from long-term valacyclovir or valgancicliovir treatment in a subset of CFS patients with evidence of active on-going herpes virus infections, also shown in a previous small study of 12 patients with elevated antibodies to EBV or human herpes virus 6 (HHV-6) [19]. We find the delayed clinical responses after B-cell depletion, that we observed in the majority of responders, difficult to explain from a viral elimination mechanism. In our opinion, this response pattern is more compatible with the gradual elimination of an autoantibody, perhaps by preferential elimination of short-lived pre-plasma cells. Although poorly understood, immune system alterations seen in stress-related diseases such as post-traumatic stress disorder could also be relevant for the effects of B-cell depletion seen in CFS [20].

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0026358

 

[beaker]

The good news is that Rituximab comes to the end of its patent in about a years time, if I remember correctly, so there should be cheaper generic versions available.

Want to jump in here --- and this may be a discussion all its own.
Unfortunately generics for Rituximab ( and other biologics) are most likely not going to be easy.
My rheumy explained to me that as a biologic agent, it is what it is and therefore Genentech is not worried at this time about generics when their patent ends.
I wish I could explain it the way he did.

I found this online that gives its own short explanation of difficulties of biological agents becoming generics :
Pillsbury Law > Newsroom > News > Path sought for generic biologic drugs
Path sought for generic biologic drugs
As mentioned in: San Diego Union-Tribune

3/15/2009
The lack of a process for producing generic versions of biologic drugs is costing consumers billions of dollars. A possible solution is one of the Obama administration’s priorities with regard to health care reform.
“The challenge here is that the science isn't ready for this,” said Richard Blaylock, a San Diego-based patent litigator with Pillsbury.
“It's not like a generic (pharmaceutical). You can't hold up two vials of antibodies–one Rituxan made by Biogen Idec and the other a biosimilar out of India–and say definitively whether they are the same as you can with chemical drugs,” Blaylock explains.
“As a result, biosimilar makers will probably have to provide much more data about the copycat to the FDA than the maker of a pharmaceutical generic would need to,” he says.
________

I know there is much more to this than I can possibly explain. Just thought I would throw it out there in this discussion to show that generics to the market for biologics are not the same as other drugs.

On the one hand, that would make Genetech more likely to pay for research ?
on the other hand, they were burned on the lupus studies and word is are not feeling so ready to jump into more trials right now.

Also to note some good news on this situation is that there has been a push by Obama to shorten the patent period of biologics to 7 years in order to get "identicals" to the market sooner due 1. the high cost and 2. the long procedure needed to get them approved. It was not approved by Congress, but there is still a push to make changes.

another article on both the problems with making generic biologics and the push for FDA changes:
First U.S. Rules for Generic Biotechnology Drugs Set Out in Draft Proposal - Bloomberg

 

[determined]

Regarding the expense of rituximab, I just wanted to add: When I was treated for breast cancer, I had a tremendous improvement in the weakness/fatigue component of my CFS. I remember looking at my bills and noticing that one of the drugs they used in treatment was very expensive ($3000 per dose), but one was very cheap ( $10 per dose ). So, my point is that there are probably other drugs that can provide the same beneficial effects as rituximab....we just need to find out which ones. It is frustrating that both my CFS doctor AND the oncology nurses commented that CFS patients being treated for cancer often get better - I think we have known this for quite a while. Perhaps progress would be quicker if we can find a cheaper drug to use.

 

[currer]

Regarding the expense of rituximab, I just wanted to add: When I was treated for breast cancer, I had a tremendous improvement in the weakness/fatigue component of my CFS. I remember looking at my bills and noticing that one of the drugs they used in treatment was very expensive ($3000 per dose), but one was very cheap ( $10 per dose ). So, my point is that there are probably other drugs that can provide the same beneficial effects as rituximab....we just need to find out which ones. It is frustrating that both my CFS doctor AND the oncology nurses commented that CFS patients being treated for cancer often get better - I think we have known this for quite a while. Perhaps progress would be quicker if we can find a cheaper drug to use.

That COULD be because of an effect on rapidly multiplying cells (such as immune cells) when an anti cancer drug is introduced (which would be designed to target rapidly dividing cancer cells) It would be interesting to know which cancer drugs have this effect in ME. Can you remember, determined?

Methotrexate is used as a b cell depletor in rheumatoid arthritis and also as an anti cancer drug and anti psoriasis drug because it blocks division and rapid multiplication of cells. I asked Dr Mella about methotrexate as it was used in the pilot study with rituximab, but he said that they felt methotrexate was not effective in ME.

You are right determined, maybe we need to bring the oncologists in on this one and see what they can think of. They may have a lot to offer on research into ME.

 

[determined]

The drugs were: epirubicin, 5FU, and cytoxan. I think that's all. Sorry I didn't see this earlier.

 

[Jacque]

Hey Yall, Well I am not as smart as all of you but I have been sick for 35 years and have reached complete disabled and livin on the couch.. Been diag with everything from RA, FM, CFS, EBV, Lupus, Lyme Disease, - and the list goes on... but ME was like reading a book written about ME... I found Dr. Kogelnick in Mountain View California and in my 35 years of seeing doctors he is by far the BEST doctor I have EVER seen... Not an arrogant jerk in his EGO... He is working with the Norwegians on their studies on Rituxan. I consulted with him and he really looks at CMV, Herpes viruses, EBV, HHV6 and NK cell function..which was all quite clear to him what was wrong with me and why I can hardly function. After reading what I could I made the decision to go for it with Rituxan. The drug is being covered for me on their patient program and I pay $1,050 per infusion. I have 6 over 15 months. I just had my first 2 days ago and it all went well - thank God!! Dr. Kogelnick has been meeting with the CDC and they are starting to take a real look at ME-CFS and I filled out their questionairre. Dr. K says there are 1 million diagnosed in US but he believes the more accurate # would be 4 million in US and 8 million worldwide!! He said when they started research they wondered if just Type A people got this illness because that was mainly what came to their office. Then it occured to him that it was the Type A's that just NEVER GIVE UP..and keep searching for an answer and finally found their way to his office. Thank God I am a Type A..and I feel so blessed to only live 4 hours from him as people are flying in from India, Norway, Canada, and Idaho, etc to get treatment bc they can be entered into the study! Dr. K explained to me that this is a intracellular infection of the B Cells. And as far as the rest that you all have been discussing I don't know. He also did mention that when the patent does run out there will be more inexpensive alternatives hopefully available by then. I am trying not to think too far in the future as I worry,, what if it really works....how the flip will I be able to afford to stay on it. I just can't go there right now... I am just glad I am moving in a forward direction and not suicidal and hopeless any more and feel like I can at least be a part of a possible solution or cure, for many generations to come. If you are all lookin for an AMAZING, CARING, Doctor that really understands this mess Dr. Kogelnick is the guy!!! I am so glad I found him. I will keep you posted on my progress! Jacque

 

[xrunner]

For those who are up-to-date with the use and effects of R. in ME, could you pls help my understanding:
- it's still not clear why and how R works?
- do we know when we could have a better idea of the above?
- how stable have the improvements been in those who responded to the drug?

 

[Jacque]

If you google Norway Rituxan ME/CFS Study you will find some good articles that explain what they have seen in regard your question. In the first study 2/3s got improvement but there were relapses. So now the new study (which I am a part of) is over 15 months to see if giving more infusions over a longer period of time will control the relapses... From what I have been told the viruses hide out in the B Cells... The Rituxan wipes out the B Cells...but in two weeks the Bone Marro starts pumping out new ones... The challenge is how to keep the new B cells from becoming reinfected. Dr. Kogelnick is open to trying an Antiviral (Famvir) with me in addition to the Rituxan. That is what I LOVE about this doctor. He listens and is open minded and wants to HELP!! Not a money grubbing, egotistical, doc! X runner I think all of this research is still in infancy but in about 1 1/2 years Dr. K's research will be complete. I wasn't willing to wait that long. Some of you may want to try Valcyte or Famvir (Antivirals) until research is complete? That was one of my options - vs the Rituxan.

 

[FancyMyBlood]

Thanks for your report Jacque. It does seem dr. Kogelnik is one of the best docs a ME/CFS patient can wish for!

Btw, who told you rituximab works because it eradicates B-cells where viruses are hiding? I believe Mella and Fluge suggested this is a very implausible mechanism, because response should be seen much sooner.

 

[Jacque]

I am just reporting on different discussions I have had with Dr. Kogelnick. He said this is an intracellular infection and it is obviously hiding out and using the B Cells as a transport system. Which as you know was discovered "accidentally" by the Norwegians treating Lymphoma patients with the Rituxan. Hopefully in a year and a half when their study is complete they will know a LOT more.. Again if you google Norwegian Study on Rituxan with ME/CFS there are some great articles on this. I wish I could remember their site.. I will see if I can look it up for you..

 

[Jacque]

I will ask Dr. K when I go back in 2 weeks. I seem to be getting a very fast response. I slept for 12 straight hours last night and have felt a "shift" take place in my body. Hard to explain. I just feel less "fluish
" but time will tell. When I go back I am gonna ask Dr. K if he would be willing to get on here and answer the scientific questions... Worth a try anyhow???

 

[xrunner]

THanks Jaque. I didn't get a sense of the latest by looking it up and also some conflicting info.
It seems to me the good thing about R is that it may not be dependent on specific infections but could work across the board as there are so many other infections that use Bs as hiding place.

 

[Sushi]

I will ask Dr. K when I go back in 2 weeks. I seem to be getting a very fast response. I slept for 12 straight hours last night and have felt a "shift" take place in my body. Hard to explain. I just feel less "fluish
" but time will tell. When I go back I am gonna ask Dr. K if he would be willing to get on here and answer the scientific questions... Worth a try anyhow???

It would really be great if he would be willing to join here and participate at a level he could handle. One idea might be a scheduled group chat! He wouldn't have to be "available" all the time, but it would be a really great thing to be able to ask him questions.

Best,
Sushi

 

[Jacque]

Sushi I am going to email him today and see if he would be open to that! He always replies to my emails...love that about him too!