Thursday, September 20, 2012

Bits and Pieces: Pharmaceutical Follies Edition

Oh, those pharmaceutical companies, always generating such tremendous tidings of joy and overwhelming warm and fuzzy feelings in the hearts of their adoring public. They’ve cured almost every disease that has ever plagued mankind, urged doctors to only prescribe their products when absolutely necessary, kept the price of medicine low enough so that even the most unfortunate can afford their wares, and have conducted their beneficent and altruistic research in a transparent, above the board manner that engenders absolute trust in all of their findings. How lucky we are to…

Whoops! Sorry, I started writing the above paragraph during a brief visit to an alternate universe, one much more to my liking, in which vintage Godzilla movies keep winning Oscars decades after they were made, bacon is a health food, blithering idiots are scorned rather than given their own reality TV shows, and I’m fluent in 10 languages, drive a mint condition 1956 Ford Thunderbird, and am a world-class triathlete. But, since I appear to have suddenly shifted back to this reality, I guess I’ll have to change the tenor of this blog post. Bummer.

I haven’t done a “Bits and Pieces” post in a while, because, well, it’s my blog and I’ll scribble what I want to. There’s been lots of stuff happening in the world of MS, and in the world in general, so in order to limit this post to a length not exceeding War and Peace, I’ll judiciously pick just which bits and pieces of info to highlight. Not that I’ve ever been willy-nilly about picking bits and pieces in previous posts, but I needed an excuse to use the expression willy-nilly, due to an obligation made in an alternate universe. We all must do our part to keep the cosmos in order, you know…

So, presented for your review are the following tidbits of mostly MS related news items, most of them having to do with pharmaceutical companies and their products, with a liberal dose of my take on things thrown in. Bon app├ętit…

♦ A study which throws into question the efficacy of the interferon drugs (Rebif, Avonex, and Betaseron) to alter the course of MS disease progression (click here) has caused quite a bit of hubbub on numerous Internet MS related forums, blogs, websites, and Facebook pages, and rightfully so. This retrospective study looked at three groups of MS patients, and tracked the course of their disease over a ten-year period. One group was comprised of patients who were treated with the interferon drugs, another of MS patients that were left untreated, and a third was comprised of patients from before the days that the interferon drugs were first made available (they arrived on the scene in the mid-1990s). The study found that patients treated with interferon were no less likely than untreated patients to experience disease progression leading to significant disability.

However, another study, which received much less play in the Internet MS universe, came to the exact opposite conclusion, finding that the interferon drugs do significantly reduce the risk of progression for multiple sclerosis patients across the board (click here).

So what’s going on here? Obviously, it’s hard to say, but, as this article points out (click here), the study that found the interferons ineffective had some possible methodological flaws. One might assume that the population of patients in the untreated group was left untreated because their disease was generally less severe and aggressive than those who were in the treated group, which would invalidate a direct comparison between these two patient populations. If this were the case, the study’s findings would actually show the interferons were effective, because they kept patients with more severe disease from progressing more quickly than those with less severe disease.

Whatever the case, the situation remains as clear as mud. The interferon drugs are much disparaged among many MS patients, because they obviously do not cure MS, cost a fortune, have very unpleasant side effects, don’t work at all for many who try them, and, to top it off, are injectables, and nobody relishes the idea of giving themselves a shot several times a week. What does seem clear, though, is that, at the very least, these drugs do offer some patients relief from debilitating relapses, even if they don’t ultimately alter the course of their disease. Many patients report a severe curtailing of their relapse rates once on the interferon drugs, which amounts to a significant uptick in their quality of life. This benefit cannot be discounted, even if interferons ultimately do prove to be worthless in stopping disease progression, which of course would be disappointing. I’m not one to defend the pharmaceutical companies, but the interferons were never approved under the auspices of stopping disease progression; rather, their approval was based on their ability to reduce relapse rates and the amount of enhancing lesions as seen on MRIs. It was hoped that these two effects would translate into a lessening of disease progression, but that was always just an assumption, a point never tested in clinical trials.

An interesting window into the opinions of patients about this issue is the comments that appear after a piece Julie Stachowiak wrote about the negative study in her always excellent MS column (click here). I expected to see a fusillade of outrage voiced by the commenters, but surprisingly, a preponderance of the comments are from patients who say they’ve benefited from the interferons and intent to stay on them because of their increased quality of life. I guess the bottom line is that, drugs or no drugs, MS sucks, and will continue to suck for the foreseeable future. Actually, that’s pretty much the bottom line about everything related to MS…

♦ Here’s an example of a pharmaceutical company snatching victory from the jaws of defeat. The FDA recently warned about seizures associated with the MS drug Ampyra (click here), made by Acorda pharmaceuticals, which is supposed to improve the ability to walk in some MS patients. Much to the chagrin of investors, this warning caused a marked decrease in Acorda’s stock price. Ampyra is given in 10 mg doses, and the FDA asked Acorda to conduct trials to see if a 5 mg dose would be as effective as a 10 mg dose while cutting the risk of seizures.

The results of this follow-up study showed that both the 5 mg and 10 mg doses of Ampyra failed to demonstrate any efficacy in regards to increased walking ability (click here). Acorda claims that this is because the methodology used in this study was different than that of the original studies. Regardless, Ampyra remains on the market in 10 mg doses, since it was previously approved by the FDA based on prior clinical study results. In a happy twist for the drug company and its investors, even though the drug failed the follow-up study, the fact that the 5 mg dose was ineffective means that Acorda retains its long-term patent rights on the 10 mg dose, whereas if the 5 mg dose have been effective copycat drugs could have been manufactured and placed on the market as soon as 2017 (click here). Acorda’s stock price rose on this news, so all is well in investor land, despite the fact that the drug can cause seizures and may be largely ineffective. So, bad news for MS patients, good news for those making money through the marketing of a drug whose efficacy is highly suspect. Talk about alternate universes…

♦ In a case that didn’t work out quite as well for the drug company, Genzyme submitted the drug Lemtrada (formally known as Campath) to the FDA, fully expecting an approval. The company was so confident that the drug would be approved that they started pulling Campath, which had been marketed for years as a treatment for leukemia, off the shelves to keep it from being used off label to treat MS. This was done so that Genzyme could hike the price of the renamed drug to fully take advantage of the more lucrative multiple sclerosis market (click here). After all, MS patients need to take their drugs for years on end, but victims of leukemia either go into remission or die, limiting their necessity to consume drugs. But, ha ha on Genzyme, the FDA turned around and requested that the company resubmit their application (click here), asking the company to change the presentation of the data so the agency can “better navigate the application”, whatever that means. The FDA didn’t order any additional trials of studies to be run.

While it feels good to see a case of corporate greed smacked back, even if only a little, Lemtrada is an interesting MS drug. It is a powerful immunosuppressant, but has been shown in studies to actually decrease the amount of disability seen in patients, even five years after they stopped taking it (click here). This is a result previously unseen with any other MS drug, and may be due to the fact that Lemtrada is such a strong immunosuppressant that it forces the body to rebuild its immune system. This is a similar mechanism to some autologous stem cell treatments, in which a patient’s immune system is completely wiped out with very potent chemotherapy drugs, and then “rebooted” through the use of an infusion of bone marrow stem cells. The effectiveness of the drug does come at a price, though, as 30% of those taking it develop autoimmune thyroid disease, and a smaller percentage develop a serious blood disorder. Unlike Tysabri, though, for some reason the risk of serious infection seems to be quite low, despite the powerful immunosuppressive characteristics of Lemtrada. For patients willing to take the risk, Lemtrada, if and when it is eventually approved, may be the most effective MS drug available. Of course, it only works for RRMS patients; those with SPMS or PPMS are, as usual, left to flap in the breeze…

Having said all that, it sure would be nice if researchers would concentrate their efforts on finding ways to combat MS that don’t tinker with the immensely complex human immune system, since this approach clearly leaves patients open to potentially lethal side effects while doing nothing to actually cure the disease. Perhaps trying to figure out why the immune system goes bonkers in MS patients would be a good place to start…

♦ Just to bolster your confidence that science is aggressively attacking some of the most important issues facing mankind, a cure for baldness appears to be closer than ever (click here). Apparently, Vitamin D holds the key, and researchers around the world are scrambling to finally solve the horrendously tragic and heartbreaking epidemic of typical male pattern baldness, which has brought frustration and shame to men longing to be hairy since time immemorial. Just think about how much time and money is being spent chasing this cherished dream, and how many brilliant minds are dedicated to it. Forget about cancer, heart disease, ALS, and even MS – rejoice, for soon baldness may be cured! I know that I, for one, even with my head full of thick, voluminous hair, will celebrate mightily when the cure for baldness is finally announced. I’ll sit in my wheelchair and feebly raise a pathetically weakened fist as high in the air as my ever more afflicted muscles will allow, reveling in the knowledge that some perfectly healthy bald men will soon be able to proudly make appointments at barbershops and hair salons the world over. It’s all about priorities, people, and mine are definitely in order.

♦ This little bit of news is funny and sad at the same time. Seems an MS suffering grandfather in Scotland forgot he was married and wed his girlfriend, getting into all kinds of trouble due to the fact that he is now a bigamist (click here). The 50-year-old claims he thought his first wife had signed divorce papers, but he apparently forgot that she hadn’t.

In all fairness to the gent, he’d been separated from his first wife for several years, and MS does cause cognitive and memory issues in many who suffer from it. Furthermore, his second wife left him a few months after they were married, and the stress ensuing from this whole mess triggered a relapse, leaving him using two crutches. I’ve had women leave me emotionally crippled before, but this guy really got the short end of the stick. Or, in his case, sticks. In related news, a new study found that ginkgo biloba, an herbal remedy purported to improve cognitive function, had no effect on the cognitive abilities of MS patients (click here).

♦ If you’re in need of a little inspiration, this (click here) infographic about the Paralympics can provide plenty of it. Recently completed in London, this international sporting event for disabled athletes embodies the best of the human spirit. Though the bodies of participating athletes may not fit the standard definition of perfect, their hearts certainly defy definition.

I’ll leave you with the following video, in which a noted brain researcher recounts her experiences during and after suffering a stroke. These experiences provided her with startling and fascinating insights into not only the workings of the human brain, but of the universe and our place in it as well. I have an endless fascination for the mysterious place where science gently kisses spirituality, and this talk navigates that enigmatic realm as well as any I’ve ever heard. It’s 20 minutes long, but I guarantee it’s time well spent, and will provide you fodder for much contemplation…

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  1. Hi Marc,

    As always, thank you for your posts. I love to read them :) And I have seen that video that you posted and it is truly amazing to listen to and watch it. I would say it could be a game changer for some. My game changed a few years before that, so it was more like affirmation of my changing game, if that makes any sense? lol! Anyhoo, thanks for your insights and humor and videos, oh my!

    David H.

    1. Thanks for the kind words, David. Yes, I think that video is amazing, and the insights she gained from her unfortunate experience (Maybe not so unfortunate, given the insights) are very enlightening. Some of the concepts she discusses are very similar to those espoused by the eastern philosophies/religions, like Buddhism and Taoism. In any event, I find her descriptions quite compelling…

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    1. Not sure if this is a clumsy attempt at spam. If it is, please go away. If not, thanks for your somewhat Confusing contribution to the blog…

  3. Those are some cool links. Quick question, in the second study on MS progression, and reason they use the conversion from relapsing to progressive MS as the measurement of success for the drugs? Isn't a slow progression still better than horrible flares? That said, the evidence did suggest less symptom progression amongst the high risk patients who took DMDs versus the high risk patients who did not take DMDs. As a guy, I am automatically not in the low risk group, so my decisions not to forgo treatment still seem justifiable.

    I loved the video. Even starting slow, when she started talking about her stroke was brilliant.

    1. Unfortunately, unless or until someone fixes us, nearly if not all "MS" patients face conversion to progressive, at which point the doctors, insurance companies, researchers, employers, the world, lose quite a lot of interest in you.

      I wonder how much efficacy has been generated artificially by the simple expedient of dividing up the "MS" population along the lines of "likely to improve anyway"? Is the difference between progressive and non-progressive "MS" part of an alternate universe, that allows a more pleasant accounting, actuarial and scientific experience of "the problem"?

      I am one of probably very many who has been left untreated because the neurologist said "no more treatment". Not because I am a less severe case. I do though, intend to stay as far from the clutches of the medical system as it exists here in my country as possible. ("Rehab? I said No, no, no.") So I try not to disturb it. I am progressing more slowly since my CCSVI procedure. But, like you, I am severely disabled and on a scale of improving, stable, and progressing, I am still progressing.

      The methodology may be quite all right. I do believe we are probably missing a lot of information by not asking: "left untreated, why?"

      Jill Bolte-Taylor is an inspiration, and her mother was invaluable in her 8-year recovery. The only problem I have with Ted Talks is that people think they have the whole story, and don't read the book.

      See "Gasland" if you want an alternate opinion on why you may be sick. See it anyway. It's on Netflix in Canada. It's an emergency.

      Baldness is very well dealt with by taking LDN. Makes your fingernails strong, too. Has anyone got the patent yet for that? If not, I call dibs.

    2. I would agree that slow progression is better than horrible flares, but many were hopeful that a reduction in relapses would translate into slowed progression as well. Progression itself is not used as an endpoint in most MS studies because most patients progress at a rate to slow for the criteria to be included in expeditious studies. In other words, the Pharma companies want endpoints that are easily quantifiable and don't take too long to manifest, so that they can get their drugs onto the market quicker. As usual, it's all about money…

      Unfortunately, once patients to progress to SPMS treatment options are few, and problematic at best.

      Regarding LDN, it is not patentable, because the drug used (Naltrexone) is an old compound that came off patent years ago. This is why no real research has been done on LDN, as there aren't scads of cash to be made from marketing the drug. Please see my previous reference regarding money…

  4. If she really believes what she said in the end then either she is God and inviting us all to accept that we are too or she is mentally ill. I felt sorry for her but as always I loved your post and her description of her experience was interesting.

  5. Male pattern baldness cured? Whew! I have been worried about that issue ever since my childhood when I watched my grandmother spend an extraordinary amount of effort trying to find a way to keep my grandfather's bald head from leaving an oily mess on the headrest of his favorite chair. I only wish they had both lived to see this miraculous development!

    1. I worry less about baldness and more about the southerly migration pattern of my hair. I always tell the barber to shave my neck because I want a break between the hair on my head and the hair on my butt. Should I worry about the effects of my taking extra vitamin D? lol

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  6. Bacon is not a health food? Since when? Maybe bacon is the cause of MS. Jump on it you BigPharm guys.

  7. As some one who has taken 4-AP (the active ingrediant in Ampyra)for four years, I can say that the use of walking speed as a measure of the drug's effectiveness, obviously does not take into account the other ways the drug can improve function. Easy enough to measure for the purposes of conducting studies and trials but there are lots of issues that can be impacted by improved nerve conduction. I have experienced that, although difficult to quantify, but for certain am very aware when I haven't taken a dose. I also have never experienced anything like a seizure (YMMV).

    As for the interferons, once again the scientific imprecision of the catergorization of MS types makes me skeptical about the ability of these studies to evaluate things like "progression", "disease activity", etc. So much variation from person to person in how MS manifests itself, much less how the disease actually works. One thing we know for sure, as you so eloquetly stated, MS sucks and regardless of what Big Pharms, the AMA and the NMSS might say, we patient generally are in complete agreement about that.

  8. Nicely done as every Marc. Here in the UK Ben Goldacre has a new book out all about the ever-benevolent Pharma industry. There's a little taster in The Guardian.
    All of it is depressingly familiar but if it reaches an ever widening audience then things will change, surely? Isn't that what democracy is all about?
    Keep up the good work.