New pilot study in the loop from the researchers at Haukeland

[deleder2k]

Studies to find out the efficacy for which diseases? Non-Hodgkin Lymphoma? RA?

Biologicals major Amgen is carrying out a global phase III clinical trial for a biosimilar version of Roche’s blockbuster arthritis/non-Hodgkin’s lymphoma drug MabThera/Rituxan (rituximab).

http://gabionline.net/Biosimilars/News/Amgen-starts-phase-III-trial-for-biosimilar-rituximab

BIOCAD approved in Russia (probably not good enough for the EMA as of today)

http://www.biosimilarnews.com/biocad-announces-the-final-approval-of-rituximab-biosimilar-in-russia

Sandoz also states that it is making strong progress on its other biosimilar clinical development programs which includes biosimilar versions of rituximab (Roche’s Rituxan/MabThera) and adalimumab (AbbVie’s Humira).

http://www.biosimilarnews.com/sandoz-updates-biosimilar-development-pipeline


Not sure if a biosimilar drug needs to be tested for different diseases. Does anyone know?

 

[DanME]

Biologicals major Amgen is carrying out a global phase III clinical trial for a biosimilar version of Roche’s blockbuster arthritis/non-Hodgkin’s lymphoma drug MabThera/Rituxan (rituximab).

http://gabionline.net/Biosimilars/News/Amgen-starts-phase-III-trial-for-biosimilar-rituximab

BIOCAD approved in Russia (probably not good enough for the EMA as of today)

http://www.biosimilarnews.com/biocad-announces-the-final-approval-of-rituximab-biosimilar-in-russia

Sandoz also states that it is making strong progress on its other biosimilar clinical development programs which includes biosimilar versions of rituximab (Roche’s Rituxan/MabThera) and adalimumab (AbbVie’s Humira).

http://www.biosimilarnews.com/sandoz-updates-biosimilar-development-pipeline


Not sure if a biosimilar drug needs to be tested for different diseases. Does anyone know?

As far as I know, this is not the case. In contrast to normal generics, biosimilars aren't exact copies of the original drug. Most of them are proteins and you always create some slight differences and variations during the synthesising process. To garantue their comparable effectiveness, the drug must undergo a special shortened clinical trial scheme. But usually only in one common disease.

 

[Snow Leopard]

But usually only in one common disease.

In any event, such biosimilars would need to demonstrate efficacy for ME to be approved in Western/developed countries.

 

[alex3619]

In any event, such biosimilars would need to demonstrate efficacy for ME to be approved in Western/developed countries.

This is very much the problem.

 

[Joolz]

I thought Prof Scheibenbogen had only used RTX and not MTX. But it may be possible.

She does mention it to some patients as a treatment they could try, but I don't know if she actually has prescribed it to her patients.

 

[Anne]

Has this been posted here?

An update on the Fluge&Mella research from one of their funders, Kavlifondet. In Norwegian (but perhaps Google translate will do a decent job for once?):
http://kavlifondet.no/2015/03/leter-etter-svar-pa-me-gaten/

 

[SaraEngland]

Has this been posted here?

An update on the Fluge&Mella research from one of their funders, Kavlifondet. In Norwegian (but perhaps Google translate will do a decent job for once?):
http://kavlifondet.no/2015/03/leter-etter-svar-pa-me-gaten/

http://forums.phoenixrising.me/index.php?threads/cyclophosphamide-and-rituximab-update.36023/

 

[Cheshire]

I haven't seen it yet.
Another interview in The Naked Scientist, University of Cambridge:

Is ME an autoimmune disease?
Øystein Fluge and Olav Mella, Haukeland University Hospital, in Bergen

http://www.thenakedscientists.com/HTML/content/interviews/interview/1001217/

 

[BurnA]

Mycophenolate is very interesting because it has been tried in combination with rituximab and if I remember rightly there were major falls in total antibody levels - which you do not get with rituximab alone. The implication is that the combination may lead to die off of long term plasma cells - which is of course what Radbruch and colleagues were hinting at being worthwhile. My information at the time was that because of the fall in total antibody the scientists running the study got worried and decided not to pursue it - assuming that it would cause infection problems. There may even have been some increase in infection.

What I think this demonstrates is that we need to devise a clever protocol that gets rid of just the right amount of plasma cells in a way that can allow background immunity to be 'topped up' afterwards if necessary. Treatment of leukaemias suggests that if you are brave you can clear the whole system out and get it to recover, but it can be hard work for patients. Anyway, I do think mycophenolate could be a key ingredient in a successful protocol in due course. The other drugs that may be useful are the BAFF antagonist biologicals like the anti-BAFF antibody Belimumab and the receptor construct TACI-Ig. Trouble is getting drug companies to work together to plan intelligent combination protocols - even in diseases like lupus or RA.

Just wondering, as combination protocols seem to represent potential treatments, do we need drug companies to work together for this to pan out or can dedicated doctors do it on their own similar to our Norwegian friends ?
I am curious if there are proposed potential treatments how easy or difficult is it for a doctor to 'experiment' so to speak.
Do such treatments take place that we just don't hear about or are doctors hands tied somewhat when it comes to combination protocols ? Thanks.

 

[Jonathan Edwards]

Just wondering, as combination protocols seem to represent potential treatments, do we need drug companies to work together for this to pan out or can dedicated doctors do it on their own similar to our Norwegian friends ?
I am curious if there are proposed potential treatments how easy or difficult is it for a doctor to 'experiment' so to speak.
Do such treatments take place that we just don't hear about or are doctors hands tied somewhat when it comes to combination protocols ? Thanks.

There has been a delay of more or less ten years in trying combination therapies, partly because one or two early studies were not very successful. As you suspect, they are hard to set up, particularly if the drugs belong to different companies. Now that there are several variants of most of the drug classes, that can be bought up by competing companies were are nearer a situation where a single company is likely to own drugs of all the relevant classes for a combination approach. I will not go into details but a lot of buying and selling of new drugs by companies has led to this situation in the last five years.

It is theoretically possible for independent clinicians to set up combination trials but the cost is a major hurdle. It is probably easier for oncologists whose departmental accountants are used to combinations of expensive drugs being used but with biologics it will be seriously tricky even for them. There are also much tougher rules on trial approval by R and D departments now. Legal indemnity needs to land on the right door mat and things like that. So in practice I suspect most combination trials are going to be drug company initiated. These are now in progress for the major rheumatic autoimmune diseases. That will mean that we can learn from these if we want to set up similar things for ME.

 

[Hip]

Mycophenolate is very interesting because it has been tried in combination with rituximab and if I remember rightly there were major falls in total antibody levels - which you do not get with rituximab alone.

Mycophenolate is a new one for me.

I just found an entry about mycophenolate in Maija Haavisto's compendium of useful ME/CFS drugs: see here.

Intriguingly she mentions that mycophenolate, although immunosuppressive, has antiviral effects for two ME/CFS-associated viruses: coxsackievirus B and herpes family viruses.

This study details the antiviral effects of mycophenolate on CVB:

Mycophenolate mofetil inhibits the development of Coxsackie B3-virus-induced myocarditis in mice

We observed that mycophenolic acid (MPA), the active metabolite of the immunosuppressive agent mycophenolate mofetil (MMF), inhibits coxsackie B3 virus (CBV3) replication in primary Human myocardial fibroblasts.

Treatment with MMF resulted in a significant reduction in the development of CBV-induced myocarditis as assessed by morphometric analysis, i.e. 78% reduction when MMF was administered at 300 mg/kg/day (p < 0.001), 65% reduction at 200 mg/kg/day (p < 0.001), and 52% reduction at 100 mg/kg/day (p = 0.001).

The beneficial effect could not be ascribed to inhibition of viral replication since titers of infectious virus and viral RNA in heart tissue were increased in MMF-treated animals as compared to untreated animals.

In table 1 of that paper, mycophenolic acid looks to be around three times better than the antiviral ribavirin in terms of decreasing virally-induced cytopathic effects in myocardial fibroblast cells.

@halcyon may be interested in this.

 

[Jonathan Edwards]

Mycophenolate is a new one for me.

I just found an entry about mycophenolate in Maija Haavisto's compendium of useful ME/CFS drugs: see here.

Intriguingly she mentions that mycophenolate, although immunosuppressive, has antiviral effects for two ME/CFS-associated viruses: coxsackievirus B and herpes family viruses.

This study details the antiviral effects of mycophenolate on CVB:


In table 1 of that paper, mycophenolic acid looks to be around three times better than the antiviral ribavirin in terms of decreasing virally-induced cytopathic effects in myocardial fibroblast cells.

@halcyon may be interested in this.

That study seems confusing. They found mycophenolate reduced viral replication in vitro but not in vivo. In general mycophenolate impairs defense against infection - in fact I think the combination study with mycophenolate and rituximab was stopped because of infectious complications. It doesn't look to me to be something I would want to give someone with an infection already present.

 

[Hip]

It doesn't look to me to be something I would want to give someone with an infection already present.

Googling mycophenolate in the context of common viruses, the general theme that came up in the search results was viral reactivation of Herpesviridae, which as you say, suggests this drug is inadvisable for those with existing viral infections / reactivations.

But mycophenolate does seem to be antiviral in a few contexts, in conjunction with other drugs:

Mycophenolate mofetil strongly potentiates the anti-herpesvirus activity of acyclovir



In the case of coxsackievirus B myocarditis, although you said in a post some while ago this was not an autoimmune disease, I think the assumption is that in myocarditis, some sort of immune attack on heart cells is induced by the viral infection; so possibly mycophenolate, by quelling this immune attack, reduces cell damage.

 

[Jonathan Edwards]

Googling mycophenolate in the context of common viruses, the general theme that came up in the search results was viral reactivation of Herpesviridae, which as you say, suggests this drug is inadvisable for those with existing viral infections / reactivations.

But mycophenolate does seem to be antiviral in a few contexts, in conjunction with other drugs:

Mycophenolate mofetil strongly potentiates the anti-herpesvirus activity of acyclovir

In the case of coxsackievirus B myocarditis, although you said in a post some while ago this was not an autoimmune disease, I think the assumption is that in myocarditis, some sort of immune attack on heart cells is induced by the viral infection; so possibly mycophenolate, by quelling this immune attack, reduces cell damage.

I am not desperately impressed by the relevance of the mouse study in the quoted paper. Systemic MMF would seem to be more relevant.

The myocarditis after coxsackie must indeed be some sort of immune attack, probably involving T cells or NK cells and it is not surprising that MMF damps that down. But in the previous paper quoted that did not seem to be due to reducing the multiplication of virus.