Wednesday, November 9, 2011

Greed Trumps Common Sense Once Again, Courtesy Big Pharma


Image by Images_of_Money via Flickr

The mix of money and medicine often makes for a strange brew. Far too often, conflicts arise between what is best for the patient and what is best for the bottom line. Over the last several decades, treating chronic illness has mushroomed into a worldwide multibillion dollar industry. To the megacorporations reaping these profits, patients are seen first as consumers, rather than sick individuals needing to be healed. This truth is often camouflaged with warm and fuzzy programs designed for patient outreach and education, but CEOs of publicly traded medical corporations, as mandated by law, are beholden to their shareholders, not to the patients consuming their company's products, a mission which is sometimes at odds with what should be the goal of all involved in the healing professions: the curing of illness and the alleviation of suffering.

We see this unfortunate circumstance play out time and time again in the world of multiple sclerosis. Since Big Pharma finances the vast majority of medical research done in the USA, promising therapies with little profit-making potential are left to wither on the vine. Thus, medical research increasingly involves only therapies that stand to attain blockbuster status. We therefore have very little scientifically reliable data on the effectiveness of Low Dose Naltrexone, dietary supplements, acupuncture, naturopathic remedies, and other largely benign practices and substances. Alternative theories about the disease, such as CCSVI, are met with a fusillade of negativity instead of intellectual curiosity, as might be expected in the case of a disease as intractable as multiple sclerosis.

One of the oddest examples of the profit motive trumping common sense involves the drug Rituxan (click here), a compound first formulated to battle B cell non-Hodgkin's lymphoma, for which it was approved by the FDA in 1997. Rituxan was the first monoclonal antibody used to fight cancer, and proved to be both safe and effective in that role. The compound works by destroying B cells, one of the major components of the human immune system. Therefore, in addition to its lymphoma fighting abilities, Rituxan is a powerful immunosuppressant. Due to these immunosuppressive properties, the drug was tried with varying degrees of success on a number of autoimmune diseases, and has been approved for use in patients suffering from rheumatoid arthritis.

Several years ago, clinical trials were started testing Rituxan's efficacy in fighting multiple sclerosis. These trials included not only RRMS patients, as is typical of MS trials, but also PPMS patients, a population for which there are no approved therapies. Phase 1 and 2 trials showed the drug to be extremely effective, dramatically reducing the amount of enhancing lesions seen on patient MRIs, and cutting by half the number of relapses experienced by RRMS trial subjects (click here). The trial results were at least equal to those seen with the drug Tysabri, which to date had been the most effective MS drug on the market. Rituxan had the added advantage of having a long history of use, which showed it to have a much lower incidence than Tysabri in expexposing patients on the therapy to to the possibility of developing PML , a sometimes fatal brain infection. Trials for PPMS were not as successful, although analysis of the data did seem to indicate that a subgroup of PPMS patients did appear to benefit from Rituxan therapy (click here).

So, it would seem that all systems were "go", and that Rituxan would be quickly shepherded into phase 3 multiple sclerosis trials, the final step needed before FDA approval to go to market, right? Well, this is where things go a little bonkers. It turns out that Rituxan's patent is due to expire in 2015, meaning that the company that makes it, Genentech, will no longer have exclusive rights to the drug, and generic versions of it could come on the market, esseessentially stripping Rituxan of its profit-making potential. Because of the complexity involved in making monoclonal antibodies, it was at first thought that the production of generics would be too costly to be seriously considered, but other companies, sensing opportunity, did indeed step into the arena (click here). Given this situation, despite the great promise shown in the earlier trials, Genentech pulled the plug on further MS Rituxan trials. Nevermind that Rituxan appeared to be safe and effective in alleviating some of the suffering caused by a dread disease, there was no money to be made from it, so any further development hit a brick wall.

Instead, Genentech did some tinkering with the production methods used to make the drug, and came up with a compound called Ocrelizumab (click here), another monoclonal antibody that destroys B cells, which was quickly put into clinical trials for rheumatoid arthritis, lupus, multiple sclerosis, and hematological cancers. By developing this new compound, so similar to Rituxan, Genentech was insured of maintaining exclusive rights to the drug for several decades, with no threat to the tremendous profits a drug equally as effective as Rituxan could generate. Ah, but the best laid plans of man sometimes go awry, and things didn't work out quite the way Genentech intended.

In 2010, Genentech was forced to suspend Ocrelizumab trials in rheumatoid arthritis and lupus due to deaths resulting from opportunistic infections attacking trial participants (click here). Of course, this was a tremendous blow to Genentech's wily plan to circumvent Rituxan's patent issues (click here), and a serious kick in the bottom line. But, alas, all was not lost, as trials continued testing Ocrelizumab's use in multiple sclerosis. Recently released phase 2 clinical trial results have shown Ocrelizumab to be highly effective in reducing enhancing lesions and relapses in RRMS patients (click here), and Genentech is now in the process of recruiting patients for phase 3 trials for both RRMS and PPMS (click here, here, and here). Apparently, the perception is that tolerance for risk is higher in the MS population than it is among lupus or RA patients, so it's full speed ahead, torpedoes be damned.

Rituxan is currently still on the market, often used off label for the treatment of MS, and has proven to be very effective in relieving some of the suffering of RRMS patients. Unfortunately, since it is not FDA approved for use in MS, many insurance companies refuse to pay for it, as it is an extremely expensive therapy (over $40,000 per year). Once the generics do hit the market in several years, the price of the drug should plummet. Should Ocrelizumab pass its phase 3 trials for MS, and be approved by the FDA, rest assured that Genentech's marketing machine will use every trick in the book to get this newer, less proven, and possibly more dangerous drug given preferential treatment over its low-rent cousin.

Of course, neither of these drugs does one whit to cure MS, but why try to cure something when treating it is so immensely profitable? Rituxan has proven to be quite effective and relatively safe (the PML rate is in the range of 1 in 100,000) when used to treat MS, and the fact that it will never even be given the chance to get FDA approval as an MS therapy simply because its power to generate millions of dollars in profits will soon disappear is nothing short of a travesty, further compounded by the emergence of Ocrelizumab, whose sole reason for existence is to sop up the profits that will be lost when Rituxan goes off patent. Might not the money used to develop and test Ocrelizumab, a figure undoubtedly in the millions of dollars, have been better spent on research that might further our knowledge of how to combat MS, rather than simply finding a way to mimic the actions of an already existing drug in a form conveniently different enough to be patentable (and, apparently, more dangerous)?

Unlike some other MS advocates, who label all of the available mainstream disease modifying drugs nothing more than snake oil, I recognize their value in improving the quality of life of many of the patients taking them. Certainly, even if they do nothing to halt the progression of the disease, dramatically reducing the amount of relapses suffered by RRMS patients has great value, and I know of many patients whose lives have been tremendously improved through the use of today's DMDs. What I can't stomach, though, is the blatant profiteering practiced by the big pharmaceutical companies, as is so clearly illustrated in the Rituxan/Ocrelizumab saga. People's lives are at stake, but I suppose in the world of big money modern medicine that concern pales in comparison with the chase for the almighty dollar.

I say shame on all involved…

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  1. This peace hits on a primary reason I pulled my money out of investing in the pharmacy industry. I made some money investing in a company because I thought it was severely undervalued based on anticipated revenue, debt, and price. I had planned to hold onto the stock as one of a semi-permanent folder of stocks I looked at and bought (only invest bonus money so no a huge amount in my portfolio, but still nice to compare to the fortune 500 every year to see I am doing better).

    Then I read There Is No Me Without You which looks at HIV and AIDS in Ethiopia in the context of a lady fostering sick kids. In the book, it goes through all of the work done to prolong patents and the millions dyeing for lack of access to treatments in large part due to our patent laws. It's sickening. We look at the Holocaust as a tragedy and question how German citizens could have allowed it without ever questioning how many millions we condemn to die with our patent laws.

    Is there a difference in culpability between those who do bad things and those who allow preventable bad things to happen? The book even states how much aid is/was promised and how the promises differ from reality. I decided I didn't want to make money from an industry predicated on trying to find a market value for life. I know my meager amount of money pulled from them won't matter, but it's the little bit I can do (in addition to writing my congressman).

    To think, I once interned at a company where we tried to determine the market for new medical drugs and technology to advise companies whether or not to proceed with further clinical trials.

  2. Shame, indeed. I also am in turn empathetic and outraged at the majority of neurologists that prescribe this crap. Empathetic in that keeping up with medicines has to be overwhelming. Outraged that they aren't keeping informed, just reading the literature. My neurologist will not prescribe LDN but will gladly put me on every other freakin' drug pushed by Big Pharm. And this is my 5th neuro. The 3rd wouldn't take me as a patient at all when I said what I was *not* willing to put into my body.

  3. This is horrible. It's embarrassing and shameful.
    Of course, they are not trying to cure us! Why would they? But it helps no one to think like that.

  4. “CEOs of publicly traded medical corporations, as mandated by law, are beholden to their shareholders, not to the patients consuming their company's products.”
    For me, it has been bizarre, as a former businesswoman with an MBA, to have moved from the perspective of the above statement to one in which I question its very foundation. Such has been the result of being stricken with a chronic, currently incurable disease. Yet, perhaps as a result of my background, I resist demonizing the pharma world. Given the parameters of that parallel universe, they are acting entirely rationally. However, I am now inhabiting another parallel universe in which things like compassion have more ascendance. And, no, I have not resolved for myself the tension between the two universes. I do know that I hate being caught in the divide between them.

  5. Tovaxin (MS vaccine) put on fast approval by FDA.

    Company stock(OPXA) is up 40%
    in 2 days.
    Tovaxin is not immunosuppresant.
    Is this real help we've been waiting for?

  6. sad and if you can stomach more confirmation of what you've written about then check this out, but be prepared to get more frustrated and angry.

  7. I am so tired of reading about advances in MS therapies on the business pages the newspaper. That's just wrong.

    It makes me want to bite something.

  8. A great informative post, if maddening. I'd never heard of Rituxan, but may mark my calendar for 2015 (when it may become generic and affordable). I've always approached my MS therapy choices as DYI, many complementary, nutritional, plus the DMD daily injection. I don't know if the injection does me any good, but its my concession to the medical establishment. Shame on those who prey upon us and generally assign a very diverse group of people the label "high risk tolerance". Not.

  9. $50,000 US for 1 course of Rituxan. Normally MS patients get 1 or 2 courses a year; that's the plan for the new drug so I'm told.

    I don't disagree with anything written here and normally don't have much love for Big Pharma but Genentech gave it to me for free.
    Perhaps they ponied up the Rituxan for more MS results? I don't think so since I'm not in a trial (I can't be accepted in any drug trial as I would skew the numbers).

    The more I read, the more I vacillate about taking another Rituxan treatment, albeit free.

    Be well!

  10. it is nice (tho that is probably not the right word) to hear my own conviction that big pharma is not interested in curing disease, but in keeping us just sick enough that we have to keep buying their drugs, and that they want to keep those drugs - regardless of effectiveness - as expensive as possible. shame, indeed!

  11. The subject of Rituxan and MS is one which interests me personally, as I am using it (for RA officially, of course). It's rather unfortunate that the companies would not follow through with trials which were headed in the right direction. Infuriating, really. At least ocrelizumab looks to be positive in MS, but those opportunistic infections in other trials are concerning.

    Just for financial reference, my insurance company pays for Rituxan because I have RA. Genentech/Biogen pick up my out-of-pocket coinsurance because I have RA. One round of treatment (two infusions) carry an approved cost rate of $23,000. Most patients would have two rounds in one year (but not necessarily).

    Since starting Rituxan two years ago, I have had the best MS and RA years so far. However, I am having the first relapse requiring a full 5-day round of IVSM in over two years. Not bad, I'd say. And courtesy of the Biogen Stratify II trial, I now know that I am JC Virus negative. Some good news to relieve the mind of the potential risk of PML.

    There is at least one Rituxan trial going on at NIH with SPMS. it's the RIVITaLISe trial (Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients with Low-Inflammatory Secondary Progressive Multiple Sclerosis). Preliminary results are looking promising so I'm told.

    Patients are still being recruited for this one but it does require spinal taps. ouch.

  12. Sue-while there is certainly good and bad neurologists (and people in general), I kind of feel that a lot of Neuros are between a rock and a hard place. They know the shortcomings of a lot of these drugs, but they also know that they to improve the quality of life of a significant proportion of patients taking them. Don't forget, it wasn't very long ago that the Neuros had absolutely nothing to treat MS with, and considered it an "diagnose and adios" disease. I'm lucky, my neuro does not even allow pharmaceutical reps into his offices at all, and his is the only doctor's office I've been in in the last 20 years that doesn't have the name of some drug emblazoned on every piece of office gear in the place…

    Nicole-the cure is going to have to come from outside of the pharmaceutical companies. There are even lobbying to have stem cells designated a pharmaceutical product, so that they can wrest control of this promising new technology. This is why funding for the NIH and independent research groups is so vital…

    Peace-you're absolutely right, the Pharma companies are acting in a totally rational way within a medicine for profit capitalist system. It's not as if there is some evil cabal pulling the strings and actively holding cures back. The entire system, as it has evolved, is predicated on generating the most bang for every research buck invested by big Pharma, and unfortunately most of our medical research funding comes from for-profit corporations. The system is rotten, there's something almost a venal about considering patients consumers first, sick people second. Again, there are no easy answers…

    Anonymous-Tovaxin is a strange case study. There was a lot of buzz about the drug several years ago, and then some very disappointing phase 2 trial results were released. Opexa, the company that makes Tovaxin almost went belly up, and little was heard about the drug for quite a while. Then whispers started surfacing that further analysis of the trial results had revealed some positive data, and the company, and the drug, came back from the dead. Although not an immunosuppressant, Tovaxin does work on the immune system, by attempting to down regulate the cells responsible for the autoimmune response. I'm not so sure that the autoimmune response is primary in the MS disease process, so I'm pretty sure Tovaxin isn't the cure we've all been waiting for…

  13. Anonymous-thanks for the link, it's like picking up a rock and finding a nest of vipers…

    Zoom-I second that emotion. It is quite telling that most of the MS research news winds up in the business pages…

    Toni-sounds like you struck a pretty good balance between alternative and mainstream therapies. In fact Rituxan is a very effective therapy, and it's outrageous that corporate politics has prevented it from reaching a wider audience. It's not a cure, but it could increase the quality of life for many, many patients…

    Anonymous-hey, if Rituxan is working for you, and you can get it for free, why not go for it? Many Pharma companies to have programs designed to help patients in financial need to gain access to their products. It's all part of the Jekyll-Hyde nature of the business…

    Wonlife-we entered a very warped reality when medicine started becoming a multibillion dollar a year industry. It's really only within the last 20 years or so that blockbuster drugs have become the driving force behind the medical establishment. And yes, there's plenty of shame to go around…

    Lisa-glad to hear that Rituxan is working for you, sorry about the relapse, though. One in two years isn't very bad, as you noted. Also glad to hear that you are JC negative, which should put your mind at ease regarding many of these monoclonal antibody drugs. Ocrelizumab unfortunately seems to be far more problematic than Rituxan was, even though it's a humanized version of the molecule. In theory it should be safer, but that just goes to show how little we actually know about the workings of the human immune system that everybody is so intent on tinkering with these days. The NIH trial on Rituxan is primarily looking at it as an intrathecal drug, based on the theory that once the disease goes progressive, a self-perpetuating immune response takes hold within the CNS, behind the blood brain barrier. The results of this trial will be very interesting…

  14. The image of Big Pharma is evolving according to a couple newly released articles. Check them out through this resource:

    1. Just a word to the wise-the website referenced in the above comment Belongs to a staunch right wing organization, which is pro-big Pharma, pro-big business, and antigovernment. Take any commentary it contains with a grain of salt, as you should information gleaned from any source with an obvious political agenda.