Friday, October 28, 2011

Rituximab, Genentech,
Tony Fauci and Pertinent Pop Culture References

As many readers are aware, a small, newly released Norwegian double-blind study found that rituximab—an IV medication used to treat lymphomas, leukemias, organ rejection and refractory arthritis—is also very effective in treating ME.  And now a bigger rituximab study is under way in Norway.

In the U.S., Genentech markets rituximab (trade name Rituxan).  In Canada, it’s Hoffmann-La Roche. And in Japan, it’s Chugain Pharmaceuticals. Unfortunately, as of this week, Genentech doesn’t appear interested in doing a study on ME. Joseph St. Martin, a spokesperson for Genentech, wrote CFS Central in an email on Tuesday: “We cannot comment on the external data you mentioned [the Norway study], but I can say that Genentech has never studied Rituxan in CFS and currently have no plans to do so in the future.”

I sent a follow-up email yesterday: “Given the success of this small double-blind study, and given the fact that CFS is a serious and sometimes fatal disease that afflicts 1 million Americans and 17 million people worldwide, I find it surprising that Genentech would have no interest in doing a study. Why is there no interest? Is there someone at the company who’d be able to enlighten me on this issue?” 

St. Martin kindly emailed back that he'd track down the right person for me to interview, but then emailed today after I followed up: “As mentioned, Genentech has never studied Rituxan in CFS and currently have no plans to do so in the future. We will not be disclosing [any] additional information on this topic.”

In my five minutes testifying before the Chronic Fatigue Syndrome Advisory Committee (CFSAC) meeting last spring, I asked for, among other things, a meeting with Dr. Tony Fauci, head of the National Institute of Allergy and Infectious Disease (NIAID), the same Tony Fauci who has said many times that ME is a psychological disease. 

I’d love to report that the two of us met over saketinis, where we chatted sotto voce about ME and then braided each other’s hair, during which time the NIAID director finally had the light-bulb epiphany patients have been dreaming about for decades:  ya know, that ME is a devastatingly serious and sometimes fatal disease.  

Alas, however, I heard bupkas from Dr. Fauci.

As Gordon Gekko might say, summer is over and business is business. I’ve been hearing the usual fretting about the toothless CFSAC committee meetings, the semi-annual snorefest of how to accomplish absolutely nothing while spending beaucoup taxpayer dollars, as suspicious guards eye patients who can barely move as if the patients are Al Qaeda operatives and the guards are Claire Danes in Homeland.

There has been some debate where to hold the CFSAC protest this year, and I say wouldn’t it be great if people could protest everywhere—the hotel where the meeting has been moved, Health and Human Services, at the homes of all government officials involved in the disease, from CDC’s Dr. Beth Unger on up. But since that’s not feasible, in my view a protest outside Tony Fauci’s office is what’s needed most to shake things up.  After all, he’s the one who dictates policy; Beth Unger et. al. comprise merely the foot-soldier battalion.

As I’ve blogged before, ACT UP patients addressed Fauci’s indifference to HIV/AIDS 25 years ago; for a time, activist Larry Kramer affectionately dubbed Fauci a “murderer.” Those strong-arm tactics changed everything for the better.  Fauci was just one of the government officials ACT UP gutted and served with fava beans and a nice Chianti. 

Dr. Stephen C. Joseph, the Health Commissioner of New York City from 1986 to1989, was another. After proposing that physicians be required to report HIV/AIDS patients to the state, Joseph became a favorite target of ACT UP. According to the Wall Street Journal, he also reduced by 50 percent the estimate of the number of New Yorkers carrying the HIV virus, a momentous shift ACT UP believed would result in diminished funding.  ACT UP staged sit-ins in Joseph’s office, tortured him with telephone calls, marched outside his house and threw paint on his house.  And, in keeping with Godwin’s Law—in which the probability of a comparison to Nazis/Hitler in a heated debate eventually approaches 1—ACT UP denounced Joseph as a Nazi.

And what did Stephen Joseph do?  When he resigned at the end of 1989, he told the New York Times that he credited ACT UP with helping change aspects of a system that had been “unfair and constraining.”

When you stand up to bullies, they back down. Eventually. Most recently, we’ve seen this caving in occur with the Occupy Wall Street protests, as the republicans began dialing back their disdain and even showed on-camera sympathy as the number of protestors and media coverage grew.

Rituximab redux
Which brings me back to rituximab. Pushing for a study on rituximab now is paramount for four reasons: one, the drug appears to work for ME, which after 30 years still has no drug to treat it; two, drug approval for a disease garners respectability for the disease—and if there’s one thing this disease needs it’s respectability. Three, figuring out exactly how rituximab works on ME may shed insight into the immune abnormalities in the disease and generate more research and effective treatments. And four, at circa $20,000 a year, the drug is prohibitively expensive and insurance won’t cover it for most ME patients, unless they also happen to have cancer, an organ transplant or arthritis.

On the down side, hobbling pieces of the immune system with a drug like rituximab may prove more Band-Aid than magic bullet.  It may thrust ME into the autoimmune world that quashes symptoms with immune suppressors rather than address the underlying disease process. That’s the world in which lupus, MS and rheumatoid arthritis currently reside. And it’s also possible that if enough ME patients improve on the drug, no one will devote much energy to searching for a cure—not that anyone does now, but one can always hope. Moreover, rituximab isn’t benign. It can be toxic to the kidneys and leave patients vulnerable to infections and cancers, as it depletes the B cells, key players in the immune system. 

Most problematic is that it can, in rare instances, reawaken the JC virus, which infects most people in childhood and is benign in healthy people, but in rare instances in immunocompromised patients it can attack the brain and cause progressive multifocal leukoencephalopathy (PML), which leads to death or brain damage. The best way to detect the presence of the JC virus is through spinal-fluid PCR and an antibody test prior to beginning therapy.  However, negative tests don't ensure that patients won’t develop PML due to the drug. For now, it's the jumbled luck of the draw.

All that being said, there’s always a risk-reward ratio for medications, and for some patients rituximab may restore life to their lives. After a disappointing summer, rituximab is huge news and certainly worthy of a bigger study. How do you convince a disinterested drug company or the disinterested U.S. government to conduct a rituximab study on ME?  Perhaps this would work: Patients could contact Genentech, Hoffman-LaRoche, Chugain Pharmaceuticals, their congressman and Tony Fauci with a clear and singular message: ME patients need and want a drug study on rituximab. Period. That could be a key message at the November CFSAC meeting and at the demonstration outside Tony Fauci’s office. 

Which brings me to my final point, Peter Weir’s amazing 1982 film The Year of Living Dangerously, with Sigourney Weaver, Mel Gibson (before he got creepy) and Linda Hunt.  It takes place in 1965 during the political upheaval in Indonesia under then-President Sukarno. Hunt, who plays a male news photographer (and won an Academy Award), plasters a huge banner outside a hotel window at the movie’s climax.  It screams in red letters: “Sukarno, feed your people.”

Tony Fauci, help ME patients.  Fund a rituximab study.


Rebel Satori Press has just published the novel Beatitude by writer extraordinaire (and my good friend) Larry Closs. The book has nothing to do with ME, but it is a great read. You can purchase the book on the CFS Central store.  Click on the book's yellow book jacket on the right-hand column on this page.  

Larry is also a filmmaker and created a terrific 1 minute 13 second trailer for the novel.  If you look closely, you’ll see a quick shot of the Beat poet Allen Ginsberg and a few shots of actor Johnny Depp (in the goatee): 

From the book jacket: 
New York City, 1995: Harry Charity is a sensitive young loner haunted by a disastrous affair when he meets Jay Bishop, an outgoing poet and former Marine. Propelled by a shared fascination with the unfettered lives of Jack Kerouac and the Beat Generation, the two are irresistibly drawn together, even as Jay’s girlfriend, Zahra, senses something deeper developing.

Reveling in their discovery of the legendary scroll manuscript of Kerouac’s On the Road in the vaults of the New York Public Library, Harry and Jay embark on a nicotine-and-caffeine-fueled journey into New York’s thriving poetry scene of slams and open-mike nights.

An encounter with “Howl” poet Allen Ginsberg shatters their notions of what it means to be Beat but ultimately and unexpectedly leads them into their own hearts where they’re forced to confront the same questions that confounded their heroes: What do you do when you fall for someone who can’t fall for you? What do you do when you’re the object of affection? What must you each give up to keep the other in your life?

Beatitude features two previously unpublished poems by Allen Ginsberg.


  1. The Rituximab study supports the human gammaretrovirus hypothesis for ME. MLVs infect B cells and Rituximab downregulates nfkappa B and Th17 cytokines. EBV for instance does not cause a Th17 profile.

    "The best way to detect the presence of the JC virus is through spinal-fluid PCR and an antibody test prior to beginning therapy. However, negative tests don't ensure that patients won’t develop PML due to the drug."

    That will come down to the ability of the test being used and those conducting the testing. Many researchers have forgotten this when it comes to HGRVs.

  2. Mindy,

    Thanks for a very nice review and some interesting comments (and lack there of). If what I have heard about Genetech's patent on Rituximab is correct, it runs out in about a year. Not patent, generics pop-up, and price, profits and interest evaporates. Not too tough to figure out where their indifference is coming from.

    On the up side, from the Government's and insurers' point of view, a potential treatment for CFS patients just got much cheaper (much more so than disability payments and Medicare for those 'lucky' enough to have access to either).

    As you point out, the focus needs to be on why a drug like Rituximab might ameliorate symptoms. More evidence that it helps and in which patients would be a welcome start down that road (and yes, MS patients might have a lot more legitimacy in the eyes of the medical establishment but they are far from having real answers for their disease).

    Thanks again,


  3. Thanks for informing the Canadian contact is Hoffmann-La Roche. I have sent my question.

  4. Thanks Mindy. Do you have an email for Fauci?

  5. Thanks Mindy. Do you have an email for Fauci?

  6. We need to write the Canadian and American governments demanding Clinical trials. We need to advertise our need for these Clinical trials to push the research forward.

    MS activists got Liberation therapy into clinical trials because they pushed for it.

    We can do the same. We need a public relations arm of ME/CFS activism to actively push for these clinical trials and not take NO for an answer.

  7. What if every American patient with ME/CFS wrote Genentech asking for a clinical trial. Wouldn't the sheer number and the possibility of doses show how much money they could make if it were prescribed?

    How did people with RA get the attention of the drug companies?

  8. To ANON 8:53 p.m. -

    Here is an article that explorers how 2 researchers persisted in showing that Rituximab was an effective treatment for RA (hint: it wasn't easy for them):

  9. Shane mentioned that the Rituximab patent rights expired soon which may not make Genentech interested in started a clinical trial on ME patients. Genentech could have said: "Our patent for Rituximab is expiring soon, but we have a new drug in the pipeline that could be just as if not more effective for your disease". however they did not say that, instead they kind of closed the door and wanted us to go away along with the disease which is even less respected than seasonnal allergies

    Rituximab is being tried in over 1100 studies, currently (clinical Diseases like cancer, rheumatoid arthritis, penphigus, Idiopathic throbocytopenic purpura, myashenia gravis, organ rejection (aka GVHD) , "stiff person syndrome", EBV + Post transplant lymphoproliferative disease (PTLD), Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM), Wegener's Granulomatosis and Microscopic Polyangiitis, Neuromyelitis Optica, Progressive Sarcoidosis, Polyneuropathy Associated With Anti-MAG IgM Monoclonal Gammopathy, psoriatis arthritis, primary biliary cirrhosis (rings a bell? Dr Mason found a beta retrovirus associated with PBH), Graves' Ophthalmopathy (from autoimmune thyroid disease), acquired hemophilia A, multiple sclerosis, Sjogren's syndrome, different kidney diseases, Behcet's disease, lupus nephritis, chronic focal encephalitis, ankylosing spondilitis, Pediatric Opsoclonus-Myoclonus Syndrome, atopic dermatitis, type 1 diabetes, ulcerative colitis, SLE (lupus), antiphospholipid syndrome and crohn's disease.

    So the Norwegians got good success with Rituximab and the americans are not interested to study it? What's up with that? Did they get pressure from CDC or NIAID or NHS and Wessley not to study it? It smells fishy to me. Are they worried about their reputation? Did they research what ME/CFS is and how debilitating it can be?

    Would Genentech consider researching another monoclonal antibody on us (that's the class of drug that Rituximab belongs to)? What would it take?

    To me it is discriminating that a company would refuse doing clinical trials on a drug that has shown through a well designed study that it is helping a particular population.

    I have visited their website, and here is the first thing one read when you visit: "At Genentech, we're passionate about finding solutions for people facing the world's most difficult-to-treat conditions. That's why we use cutting-edge science to create and deliver innovative medicines around the globe."

    i think they better take back what they said to Mindy because they are not speaking very well about what they are all about.

  10. Thank you for the excellent post Mindy. I like your suggestions.

    You mentioned that Rituxan might get us better enough that we can be ignored. I think quite the opposite. they are doing nothing for us now and we have lots of trouble fighting back because we are so sick and bereft of resources. Some of us getting substantially better could add a lot more advocacy muscle to our cause.

    Who has contact info for Gennentech, etc?

  11. dsdmom on a forum noted that Rituxan's patent runs out in 2015. Sounds to me like why they wouldn't want to do a trial.

    "Looks like genentech's patent expires 2015 for Rituxan. So if it takes a couple years to get a study going then a couple years to do the study, it wouldn't make much sense for them $ wise since it'd be off patent by the time the results came out. I read that Dr. Reddy's Laboratories in India launched Reditux (their version) in 2007 and may look to bring it here as a generic in 2015.
    Source: "

  12. Found another source stating the following regarding the patent on Rituxan (Rituximab): "Roche has claimed patent protection for the drug until at least 2015 and possibly 2018 in the USA and 2013 elsewhere"

    From here:

  13. good one. Love the snore fest part.


  14. Thanks for covering this, Mindy. The story has had such a big impact in Norway that Bjørn Guldvog, Deputy Director General of theNorwegian Directorate of Health made the following statement: "I think that we have not cared for people with ME to a great enough extent. I think it is correct to say that we have not established proper health care services for these people, and I regret that." Dr David S. Bell, who has been treating ME patients who first became ill in an epidemic outbreak in Lyndonville, NY, that affected 220 people, said in an interview on Norwegian TV channel Nyheter: "I've not seen results like this in any medical study in the 25 years that I've been in this field. So that these are extraordinary results."

    It's frustrating to see the company that makes the drug being so useless in taking the research forward. Their stonewalling response to you is a disgrace.

  15. Thanks for being a voice of action in our community, Mindy.

    Like Kati says, lists over 1100 studies with rituximab. I see 411 of those studies are "recruiting" or "not yet recruiting".

    Perhaps we should be asking the drug companies what it would take to get onto clinical trials with rituximab. I believe they may have interest, just no current plans.

    And maybe we could ask the Norway researchers, if they were given more funding, what could they do with it?

  16. Hmm .. the gov't site says ..

    NCI: [Rituximab is a] recombinant chimeric murine/human antibody ..

    I wonder if its partly murine nature suggests another mode of action within us. I suppose they could trial a non-murine equivalent antibody to exclude that possibility.

  17. I think it may be difficult to get Genentech to do a trial for the reason Justin mentioned- they aren't going to start a trial when their patent is expiring in 2015. It is really expensive to do large studies. But, it is important to note that the vast majority of the 1100+ rituximab studies are not being run by Roche/Genentech. I know at least some researchers in the US are looking into running rituximab trials; what we need is the NIH and other organizations to sponsor as many studies/trials as possible of rituximab and other promising treatments. We don't need (or want) to depend on the pharmaceutical companies.

  18. Fauci is and has always been the problem. He's the gatekeeper at the top for the NIH division my brain is too dead to remember.

    Please correct me if I'm wrong, but many biotech meds, such as monoclonal antibodies are hard to duplicate, i.e, make generics from.

    Genentech's lack of interest is stunning. Thanks, Mindy for a good blog


  19. The patent for Rituximab is running out soon – that's why they are not interested.

  20. As other people have pointed out, the reason that Genentech are not interested in trialling rituximab for ME is because they will not recoup their investment since the patent is soon to expire. Apparently, rituximab has also been trialled for MS – with favourable results. However, the research was abandoned – for the same reason, no money in it for the drug company. The pharmaceutical industry cannot afford to fund research which will not yield a profit – they would go out of business. We really need governments to get involved in funding trials for drugs which are not going to be profitable for the drug companies. The position with Rituximab and MS highlights just how ridiculous the present system is. It seem that there is a very real possibility that MS patients will be offered another drug which has no therapeutic advantage over Rituximab, but which has significantly greater adverse effects.

  21. There is no money in it for them because patients have a life long infection caused by HGRVs, which will need treatment with drugs like ARVs.

  22. I just watched a video of a great presentation that Dr Peterson gave in Sweden earlier this month. He said that he is working with Roche to get a clinical trial going for rituximab ( at 11:20.) I think Genentech's quote about having no current plans to do a trial on rituximab in ME/CFS may just be standard boilerplate and doesn't reflect the conversations going on behind the scenes.

  23. Dr Peterson does not say he has a trial going and is now talking about HGRVs being involved in ME. The same viruses found in Lombardi and Lo et al.

  24. Is this the supposed to be a consolation prize?

  25. Do you have e-mail addresses and office addresses for Fauci? If we all e-mailed him about getting a drug trial for rituximab would that help?

  26. Mindy, I dare you to use the snorefest remark at the next CFSAC next week. We must do all we can to wake them up and change what goes on at that wasteful meeting.

  27. Crikey mikey, it scares me to think what rituximab would do to my poor little personage. You know, I have recurrent viruses and knocking out my b cells would, I think probably kill me. That isn't really what I would call a cure.

    As for the artistic quest of your friends Mindy, I remember the days when I wondered about those questions. But ME is a thief which robs you of your energy and that is not all it takes. It is surprising what it reveals about love... I realise now that what I once took for a sea is a forest in which every tree stands by its own means, though none are alone.

  28. Apple now has Rhapsody as an app, which is a great start, but it is currently hampered by the inability to store locally on your iPod, and has a dismal 64kbps bit rate. If this changes, then it will somewhat negate this advantage for the Zune, but the 10 songs per month will still be a big plus in Zune Pass' favor.
    Buy HGH

  29. I personally use this medicine i think its very helpful for the peoples, before using this i m feeling so much tired but now i m feeling so much active & concentrate on work. Genetech is one o the best resource which i used & it will be very beneficial for me.

  30. I foggy forgot that we were dealing with pharmaceuticals.

    My colleague developed a patented product with them. When it came time to clinical trials, he was dismayed that they wouldn't pay for the trials. He said it would only cost the company dollars or tens of dollars. In the end, the doctors and pharmaceutical arrived at an agreed price.

    With Rituxan, it would probably only cost them dollars or tens of dollars to pump out another infusion. Hopefully the clinical trials people will get a much lower than market price.

    Luckily there's competition by the generics. Samsung and at least a few other companies are making Rituxan. The recently off-patent Lipitor generics can sell for one seventh the price of brand name. I understand Rituxan goes off patent this year in Europe and off patent in the USA in 2015?

    17 million patients multiplied by $12000 for two doses amounts to a 200 billion dollar market. Even at generic prices, 20 billion dollars is substantial.

    I hope they give our clinical trials a very good price.


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