37 replies to this topic

[scuba]

Tedsey - I sent you a private message, not sure if you are getting it (mailbox full?).

Michael

[CallMeLucky]

I agree Frank, but the cynic in me (and the investor) knows that money goes towards money.  So while the scientists/doctors want to find a cure, I don't think it is conspiracy theory to believe that research that will yield a higher return (i.e. life long drug treatment) may seem more appealing to an investor than a potentially lower yielding return in the form of a fixed treatment time frame.

Drug companies want profits, Novartis all but passed on Gleevec because in their estimation, even if the drug worked, the cost to produce it was not going to be worth the return based on the fact that not that many people get diagnosed with CML.  It was only after they saw how well it worked and that it would keep people alive for may years did they realize how profitable it would be.

Never underestimate the profit motive, or even worse, the no profit motive.

[Tedsey]

Frank,

I don't feel I accused anyone.  I used the words "skeptical" and  meant "when doctors feel" they deserve kudos, not that they all do.  I feel being skeptical is different than accusatory.   And I agree that most scientists are on the level.  I just get skeptical when there is money to be made.  Shareholders/investors, (this population includes people in various professions), have a lot of sway in all arenas despite the best efforts made by the most moral and ethical humans.  Sorry to get political, but I think the USA has a hard time with this these days, especially those on the investment front.  Why would it not spill over into our world?  I cannot help it.  Maybe because I have had such horrible experiences with some research doctors.   I guess I am a little jaded.  I had an onc who tooted her horn all the time (she is a researcher).  She felt she could cure me by a SCT and I was a fool to go the TKI route.  Everyone is entitled to his or her opinion.  However, I disagreed and found a new onc.  My days of blind faith are over I'm afraid.

Teds  

[GerryL]

Hi Tedsey,

FYI - the following has popped into our news here

German drug maker covered up warnings about thalidomide risk

Read more: http://www.smh.com.a...l#ixzz23ToQEskX

[pamsouth]

Hi Tedsey,

If I were a bit jaded about the drug and medical professional before, they have sure gave me enough reason to be jaded now.

After taking care of a dying mother for 3 years, Dealing with the medical and hospitals, let alone dealing with how the Medicare and billing & insurance all works, including my not so good Blue Cross that Sucks!!.  Then being a care taker for my husband for a few months, while his doc was overmedicating him with pills he was allergic to.  My son was in the hospital for a total of 88 days.  I remember after being diagnosed with CML in 2005 and my primary doc told me to ask my onc about getting a colon scope and I did, she said go ahead.  Then when I go for the scope I hear the nurse telling another nurse her blood pressure is awfully low.  The other nurse says leave it up to doc to make the decision.  Well they went ahead with the scope.  Let me tell you I begged the doc on several occasionals to please stop it hurt, did he stop, nope, not until he cut that d...  poly that was in a kink.  My primary asked me recently to get another scope I told her what happen, she said well your blood pressure was to low they couldn't give you much of anything.  Don't you think the good reputable doctor could have said something before he started.  Nope it was all about the money. Got darn good reason to be skeptical!!!  It's all about the money!!!  That's what makes the world go around, including congress.  Where are the promised cures.  Actually the SCT is the only cure, you would have thought by now they would have used some of this money to come up with a safer transplant.  Well maybe when they make enough money of these drugs.  What about all those donations to the Jerry Lewis telethon, well is there a cure for muscular dystrophy.  Nope,  years and years go by and billions of dollars of donations for HIV, I ask you is there a cure for HIV  NO!!, just more expensive patents to try to keep them alive, a miserable life.  Yea I know lots of cancers lot of diseases, but we sure do have a lot of expensive technology, just no cures!!

PamSouth,  Skeptical

[BethG]

Trey,

I read this post with great interest. I've been on ponatinib for over three years now (I was one of the early participants in the Phase I trial and I have the T315i mutation). The drug has been doing its job at keeping the CML at bay, but I have had some issues that have made me wonder if it was due to the drugs. Virtually everyone I personally know in the drug trial struggles with dry skin/rashes. I've had the abdominal pain off and on, and had an increase in blood pressure/triglycerides.

Over the past year, I have had a major tear of one of my calf muscles and for the last few months I've been experiencing severe pain in my left hip/low back. My working theory has been that I've managed to aggravate something in my hip, but the drugs slow down my body's ability to heal. I have no proof of my theory, but wonder if the FGFR inhibition could be leading to my slow recovery?

Overall, I much prefer ponatinib to Gleevec...I happily trade dry skin and some of my other challenges for the weight gain/frog eyes/gastric distress of Gleevec!

BethG

[Trey]

Beth,

Good to hear your inputs.  Easier damage to ligaments and tendons as well as slower healing has been a problem with TKI drugs.  I would not doubt that Ponatinib, with its additional inhibitors, has a similar or worse issue.  These are the kinds of issues that are not reported during clinical trials (they likely do not have your issue documented) and only come out over years of use by large numbers of patients.  FGFR inhibitors are too new to know much about how they affect large numbers of patients.  However, I will hasten to say that side effects go with the territory, and the drug has done wonders for some of you with T315i.

The reason I am personally displeased about the FGFR inhibition in Ponatinib is that it did not need to happen.  There are 4 types of FGFR kinases (FGFR-1, 2, 3 and 4) and Ponatinib inhibits all four, which is hard to do unless you really try to do it.  Many FGFR inhibitors only inhibit one or two types of FGFR, but inhibiting all 4 could not be accidental.  The reason this multi-inhibitor approach in drug development is done in general terms is to avoid the long process of developing several different drugs, so they include several inhibitors into one drug.  This reduces cost and regulatory issues surrounding the development of separate drugs.  So the main purpose for Ponatinib over the longer term will be for cancers unrelated to CML, such as prostate cancer, bladder cancer, etc.  Good strategy, but suboptimal for CML patients.

[pamsouth]

Tedsey,

I believe you mentioned these TKI drugs, were long time, in clinical trials, before being approved by FDA.

To the best of my knowledge these drugs (TKI) were not in long clinical trials.

Sprycel was approved May 2009 afater 24 months of clinical trials and accelerrated for approval by FDA.I have pasted the link below, I believe that is what it said.  You can read the article and interpret it yourself.

SPRYCEL

http://www.fda.gov/N...s/ucm231409.htm

Pamsouth

[CallMeLucky]

I don't want to cast anyone in a negative light here, but I think we need to recognize the elephant in the room; WE ALL HAVE A DEADLY FORM OF CANCER!  Without these drugs most of us would be dead or dying.  Sprycel has saved a lot of lives, the same goes for Tasigna and more so for Gleevec.  Are they perfect? Absolutely not, far from it, but compared to what they put in people with other cancers, they aren't that bad.  My FIL had a brain tumor and was dead 7 months later, if you ask me it was the treatment that killed him faster than the disease.

Like anything else I don't think we should accept the newest greatest thing without scrutiny, but I think many of us would be very unhappy if they held these drugs in trial for years and years and kept them out of our reach, wait scratch that, our families would be unhappy, we would be dead.

So please don't think I am being a jerk here, but we really need to appreciate the magnitude of what we have here.  We also need to recognize that we are all individuals and everyone's experience with this stuff is going to be different for various reasons.  So what may seem like a dreadful drug to you based on side effects may be perfectly acceptable to someone else and keeping them alive.  The fact we have Gleevec alone is amazing but to have second and third generation shows true initiative by scientists.

The world is an imperfect place, but given the cards we were dealt we have to appreciate what we have (and I know deep down we all do)

We hate the disease and we want it gone, it is frustrating that there is no cure, but even if Gleevec is slowly killing me and in 20 years my heart or liver gives out, how can I be anything but grateful?  CML would kill me within 3-5 years, anything we get beyond that is bonus time, whether we like the way that sounds or not.....

Just my opinion of course......

[Happycat]

Yes, it is true that pharma needs to make money on their products. However, it is also true that the scientists generally have huge egos and would trumpet any success in the war on cancer.  And let's face it, curing cancer is the HOLY GRAIL in medicine right now. These researchers aren't looking to buy more time for their patients, they are looking to cure them for good. Imagine the glory!  Nobel prize?  Most  definitely.

So I wouldn't expect scientists to keep ideas for potential cures under wraps, in favor of keeping patients on drugs to milk them for more money.   (Well, they keep it shrouded a bit, so no one scoops them).  The fame and glory that would go along with a cure is just too powerful a draw. They will always work on curing cancer.

Mind you, many people go into cancer research looking to help others. I'm not trying to diminish that. But I gotta say, the glory that comes with finding a cure, a real genuine cure, has got to be a big motivator, too.  

Traci

[chriskuo]

And the US patent system can generate huge financial rewards.  The system generates a lot of R&D activity and a lot of great drugs, but there is a tremendous monetary cost to

our society.

[CallMeLucky]

Traci - your scenario would be more realistic if the scientists are self-funded, which is quite rare.  The majority of scientists work for large corporations that have administrators making decisions on where funds go and those decisions are based on Return on investment analysis.  The administrators in the majority of cases will be completely indifferent to what the drug does or does not do, it is not their job to care, only to make sure the company is profitable.  So to be clear I am not suggesting that anyone is hiding the cure, what I am saying is that if the road to cure does not yield enough profit, I think it is unlikely that road will be pursued.  I work in technology and have lots of goals for systems I would like to build, if I had unlimited resources for software and hardware I could build some very innovative things.  Likewise a scientist can have all the dreams and altruistic intentions in the world, but unless they have the resources to realize those dreams it's not going to happen.

[BethG]

Trey,

Thank you for this reponse. I'm sort of derailing the conversation on this particular thread, but I appreciate the validation of what I was thinking!

General Comment:

For myself, I feel like these last three years (since I started ponatinib) have been a gift. I was on the path to a transplant, even had my informed consent meeting on the transplant ward at the hospital I was going to. I absolutely knew in my heart I would not survive the procedure at that facility. I chose to stay on the drug trial. It has not always been easy, I'm constantly dodging/managing side effects. I've never gotten to PCRU, but gotten extremely close a few times. I don't always feel great or have the energy I'd like to have. But, I've been able to watch my nephews grow up (three years ago I didn't even know if I would be able to meet one of them as my sister's due date was in the middle of my scheduled transplant); I've been able to keep my job; and I've been able to keep riding my horse (not as often or as enthusiastically as before CML, but I have been able to keep at it).

It is hard to mentally manage the reality of a disease like ours...we don't cut out the cancer or burn it up with radiation. The best option is life-long management with TKI's...and that option is very hard sometimes. Some days, it is hard to look at my pills and know the fog will descend in three hours after I take them. Or, even better, it is really, really hard to choose to take my pills when I re-start after a "holiday", knowing I will go through 5 days of intense bone pain while my body adjusts. But, I keep at it, because that is the best choice for me to be able to live my life and have precious time with my family..

Anyways, I think I've rambled a bit here.

Gentle Hugs to all the CML survivors here!

BethG

[wallystl]

Beth-  Thank you for your most recent post!  I became so aggravated here 2 days ago that I stopped posting.  Several people here took a bizarre posture about Ponatinib, the very drug that has both saved my life and kept me from a transplant.  Many of the posters seemed to completely miss the point that while THEY had a treatment that apparently was working for them, I didn't. 

So the trial summary in the W.P. was good news for us.  I've become pretty pissed and disappointed by several people here with their passive/aggressive manner of discussing my savior, Ponatinib.  Difficult to listen to armchair quarterbacks with no skin in the game talk about all the problems with research, pharmaceutical; companies, doctors, so on.  I could care less about all of those things right now.  In 3 years I've failed on 3 drugs and I'm barely hanging on here trying to get my son through high school.  Of the 499 in our trial, 18 died. Others are doing better that I am, some worse.  We're still here is the point!

[BY196]

I deal with large companies a lot in my line of work, and I have friends who work in medicine/pharma, and I agree with your analysis, Lucky. Corporations are allowed to pursue whatever profit-making activities they want (as long as they're legal). We still need government funding for basic research, which is (with any luck) where enough will be learned about leukemic stem cells to show the way to a cure.

Beth

[BethG]

Wally,

I can understand your aggravation. I didn't take the comments as a direct hit on ponatinib, even if they were phrased that way. I took them more as a general frustration at the options we have especially since some of us are really struggling with our responses (and side effects) to the drugs on the market, etc. It is hard to be excited about treatment when you're not feeling well or very worried about your future.

When I started the ponatinib trial, I was one of the very first T315i'ers to ever take this drug. I joined the Phase I trial about six months into it. As my doctor put it, it was a "leap of faith." And, for me, it was a Hail Mary effort to live. And, in my case, the gamble paid off.

At one point in my life, I gave consideration to conspiracy theories, but I generally no longer do. Seeing the gossip that goes around the barn with 20 people or so shows me it would be massively impossible to have a cover-up on the scale that would be required at a Big Pharma company...eventually some whisper would get out somewhere and blow everything wide open.

Hang in there...enjoy your son and your life. It is a gift. And, the good news is that all of us feel well enough to get on these chat board and express our opinions... That must count for something.

BethG

[Happycat]

Lucky,

Gotta say I still disagree. Gleevec is a case in point. It almost didn't go to clinical trials, because they doubted it would be profitable enough due to a small patient population. But they still went ahead with it. Why?  Part altruism, certainly. But also partly for the possibility of reaching that brass ring and finding a cure for cancer. The glory and enhanced reputation is important for companies, too. They get more investments, research grants, the benefit of the doubt from NCI and NIH, etc.  There is also the ethics issue.  When you can cure someone of a horrible disease that would otherwise kill them, it's gotta be darn hard to say no.    Ii think that is what made them go forward with gleevec.  There's a lot of good reasons to pursue certain avenues of research.

True, many scientists have been bitterly disappointed when their drug program is shut down by management. But that usually happens with some sort of data to indicate it doesn't work as well as thought, or has some toxicity issues, or the biology underlying the program turned out to be more complex than thought. I'm sure some get shut down for profit reasons, too, but they do consider the compassionate needs.

traci

[CallMeLucky]

I respect your opinion Traci, you are closer to this in your line of work, I've just seen enough in life to be a bit jaded.  I do believe there are good people and there are good intentions.  With regard to Gleevec, my understanding is that they went ahead with it due to public pressure.  Patients had become aware of the drugs potential and pushed the company to move forward.  So in that case it appears there was some external pressure.  Regardless I don't believe in conspiracies to shut down programs that would cure an illness in favor of one that would simply treat it, but as I said before, money chases money.  I would love to be wrong.