The Avastin Controversy and 12BarBlues

Some of you may remember last year the FDA began consideration to not recommend Avastin as a treatment for late stage breast cancer. There was speculation at the time that this was the first “death panel” decision from ACA’s advisory panel. Originally it was believed to prolong life for anywhere from 6 months to several years but then some conflicting results started coming in and the numbers were revised downward for 30% to 60% of patients. I’ve heard the costs per month given as anywhere from $8,000 to $20,000, which is pretty confusing in itself. Doctors appear to be split in their opinions of its effectiveness and whether some of the side effects are worth it.

The reason I bring this up is because our own Plumline friend 12BarBlues has recently been diagnosed with stage 4 breast cancer with bone mets and is beginning a clinical trial as soon as tomorrow for Avastin. She gave me permission to mention her situation as she thought it might encourage some of us to be more vigilant. I won’t share her private thoughts and concerns but I thought some of you may want to send a prayer or wish her way and she seemed interested in sharing what she finds out regarding Avastin, so I’ll keep you posted if I hear anything new. As a cancer survivor, it’s my understanding 12Bar was only able to acquire major medical coverage, and so her situation is less than ideal financially regarding her treatment, but she’s a survivor and hopefully she’ll prove to be one of the success stories of the trial.

This is one of the most recent articles I could find on Avastin, the controversy, and what doctors are saying.

FDA commissioner Margaret Hamburg has yet to finalize the decision, but some insurers have already decided to stop paying for the $8,000-a-month drug. Others, including the federal Centers for Medicare and Medicaid Services, announced they will continue to cover the drug regardless of the FDA’s decision.

Avastin’s use for lung, kidney and brain cancers hasn’t been challenged.

Dawood, of Dubai Hospital in United Arab Emirates, and her colleagues sent the survey to about 3,000 cancer doctors. Only 564 responded, however, limiting how representative the new findings are.

More than four out of 10 doctors said they would continue to use the drug under certain circumstances even if the FDA rejected it, and eight percent said, “of course I will use it.”

A fifth of the respondents said they would not use the drug at all, and nine percent said they would be reluctant to use it.

49 Responses

  1. Also, if anyone wants to email 12Bar with best wishes, please email me and I will give you her email address. I hesitate to put it up here but she indicated you can never have too many friends.

    Like

  2. So, so, so unbelievably sad to hear about 12bb. I will certainly pray for her and her family. If she's not checking in on the blog, please be sure to pass on my well-wishes.I'm a little confused about the controversy regarding Avastin – is the FDA decision limited to breast cancer? Or will it also apply to metastasized breast cancers?

    Like

  3. I'm not sure SCat, I know they're talking about late stage breast cancer in particular but I'd have to do more research to discover more. I remember the controversy last year but not all of the details. As far as I know they're still recommending it for other forms of cancer.I'll pass on your prayers.

    Like

  4. I'm very sorry to hear this. If it is at all helpful, I'm happy to go through some of the trade press stuff I have access to.

    Like

  5. NoVA, that would be awesome. You can email me with it if you want or put it up here. Maybe some of it will be useful to 12Bar.

    Like

  6. Prayers for successful treatment for 12bar.

    Like

  7. will email you, lms. I'll give you a heads up before i do.

    Like

  8. She will definitly be added to the prayer list.

    Like

  9. This is horrible news, and I will certainly say a prayer for 12bb. I unfortunately know more about breast cancer than I ever would have wanted to because of my work. I hope I can clear up confusion about FDA approval issues, though. Avastin has no approved indication for breast cancer now (since it was revoked earlier this year). Except for its effect on insurance coverages and any influence it might have on a prescriber (not much, typically), however, this does not affect how doctors and patients can use it. FDA does not and may not regulate medical practice, and physicians can prescribe any lawful drug for whatever they believe in their judgment is appropriate. So long as Avastin is approved and marketed for any indication, therefore, doctors can prescribe it as they see fit. In addition, it can be used for investigational purposes (trials).

    Like

  10. Yes, btw, it is still approved for four other forms of cancer.

    Like

  11. SCat:Avastin approval was removed for metastatic breast cancer as well. It was fast-track approved over the concerns of the outside advisory panel and later shown not to prolong life for breast cancer patients.I hope the clinical trial works out for 12BB.

    Like

  12. QB- Great information. The pharm company also can't advertise and market for using Avastin as a treatment for breast cancer, right? As you said I doubt that will havce much of an impact on doctor's doing so. My sister is an oncology nurse, so maybe I'll ask her if she knows anything.

    Like

  13. ashot, correct. FDA takes the position that the FDCA prohibits "off-label promotion," and FDA and DOJ have been very aggressive in pursuing enforcement actions. I think someone posted a link to a story about one of these settlements recently.This issue is controversial, though, and SCOTUS has yet to rule squarely, although it may soon. There is a significant 1st Amendment issue, because, while the 1st does not protect fraudulent speech, for example, "off-label" is not per se fraudulent. An off-label use might be safe and effective even though unapproved by FDA. Indeed, in some instances, off-label use is the medical standard of care, i.e., a physician could be negligent for not prescribing off label! Yet the drug or device company could be prosecuted for saying its product is safe and effective for that use. Some years ago, pedicle screw litigation was a momentary rage. It was off-label use that the leading surgeons said was absolutely the best treatment option and the standard of care for many patients, but the manufacturers were all sued for marketing their products with knowledge of their off-label use. It's a kind of bizarro world.

    Like

  14. Others, including the federal Centers for Medicare and Medicaid Services, announced they will continue to cover the drug regardless of the FDA's decision.What does this mean? Does M/M have a different drug policy than insurance companies, or is that something everyone else already knows and I'm just clueless.

    Like

  15. One of the resident scientists could probably speak to Avastin's mechanism of action better than me, but it is an inhibitor of angiogenesis. One of the traits of cancer, or one of the things a tumor needs to do to be cancer, is supply itself with blood via blood vessels, aka, angiogenesis.

    Like

  16. Lms, please feel free to pass along my email address to 12 Bar. If this is a new diagnosis and she's starting an Avastin trial, the reason may be financial. Trials pay for drugs. There are many drugs that are used in stage IV breast cancer with bone mets and they do buy time. If they're already approved for use, though, they have to be paid for out of pocket, through insurance, or through Medicare or, possibly, Medicaid. And Avastin is not unusual in terms of the cost. These drugs cost a fortune.Hang in there, 12 Bar.

    Like

  17. ashot,the rules on what pharma can say to HCP's in the field of cancer and virology are dirrerent, so they probably can, to a limited extent, talk to Oncologists about off label stuff. That being said, there probably is zero clinical data on any given oncological drug that is not known, or disseminated within minutes of publication. In a lot of cancer trials, the protocol is open, not blind or placebo controlled, and patient status is often know as the trial progresses.

    Like

  18. CMMS isn't my forte, but it means basically just what it says: the federal programs will continue to cover it. The feds set their own coverage rules and parameters. Private insurers companies all establish their own as well or, getting down into the weeds, most of them develop their complex policy structures and coverages with help from Pharmacy Benefit Managers and with advice from their own Pharmacy and Therapeutics Committees. The PBMs are large companies filled with actuaries, scientists and other inscrutable bureaucrats. The PTCs are advisory boards of physicians and pharmacists who advise about what drugs and procedures to cover and how. Should X be covered? For what and when? Only after Y and Z are tried? Etc. The government makes its own rules, though, and CMMS is obviously an 800-lb gorilla.

    Like

  19. I have no particular expertise to offer, so I'll just pass along my best wishes for a speedy and full recovery.

    Like

  20. QB:We talked about off-label use in the comments of Mark's PLIVA post.Your description of Avastin's mechanism of action is perfect. Avastin is an antibody that blocks a growth factor responsible for angiogenesis (VEGF).

    Like

  21. QB, there was a glory period in the early aughts when we could talk about a drug's off label data as long as it was published in a peer reviewed journal. That changed when PhRMA came about. A lot of what companies can and cannot due as well as what they can and cannot say is based not on law or regulation, but on PhRMA guidelines. That being said, there is great sport in drug companies ratting out other drug companies for illegal marketing practices.

    Like

  22. Good points made by Troll. I haven't done much work specifically related to marketing of onc drugs, strangely enough, although I have much exposure to oncologists and cancer research, diagnosis and treatment. Trial and treatment developments seem to disseminate in real time.

    Like

  23. Thanks for all the insight you guys.ABC, I passed it along to 12Bar. I'll send you hers as well.

    Like

  24. Troll:Do you work with antivirals? Professional interest — I'm a virologist.

    Like

  25. Troll, I would agree with that in part, in that PhRMA reacted to FDA/DOJ's aggressive stance by adopting precautionary guidelines. Actual court rulings have been mixed, but the stakes can be so large that companies have been hesitant to push the envelope. One court years ago held the FDA's guidelines on reprints overly broad, but it is a difficult area for drug manufacturers to navigate. The feds have reaped billion-dollar settlements and prosecuted some people. I forget, are you still in the industry?

    Like

  26. Mike, The only anti-viral I've ever sold was Famvir. Really not in the category you're probably experienced in. Had some friends that were in the HIV/Hep C field though.QB, tangentially. I sell a antibiotic direct to dentists that is used for Periodontal disease. It's actually listed as a medical device. Because of the FDA's agressivenss, we recently pulled all our marketing material for review. JnJ used to own us and the new company (much, much smaller) doesnt have the in house legal staff that can counter FDA challenges. It's ironic that since we're tiny we tend to fly under the FDA radar, but because we're smaller, we do not have the financial resources to pay a fine if the dice roll doesn't go our way.

    Like

  27. Can I ask another question for clarification? Are some, all or none of the off label uses approved by insurance companies? Or is it just certain classes of drugs that they don't cover? I guess I'm still a little confused.

    Like

  28. lms,Not sure I can give an authoritative answer to that (well, sure I can't) other than that there aren't any universal rules. Some companies definitely will pay for some off-label uses. It would be crazy not to in many cases. But other off-label uses they might not. It is case by case. Sometimes they might require an additional certification, or step therapy. It just varies.This is part of what PT committees help them decide — which uses for which drugs to cover. I know people think they are in the business of just denying coverage and finding reasons not to cover people, but that's not really how it works. They have doctors and pharmacists who advise them about what should be covered.All that said, I would not be surprised if ABC is right, because some insurers may not be paying for Avastin for breast cancer, while it would be free in a trial.

    Like

  29. Thanks qb. That's pretty much the way I thought it was. I was prescribed an off label once when I hurt my back because of the nerve pain. When I got it home and read the instructions and possible side effects I returned it to the pharmacy for disposal. Maybe I should have given it a whirl. I doubt the insurance company even knew or cared what it was being prescribed for anyway.

    Like

  30. Very likely the case. Then every now and then the insurers and union health funds decide to sue a drug company and claim they paid too much because of off-label promotion and use. These cases are 99% bs imo, so I don't exactly love the insurance companies. I've seen some really bad behavior like this, but since it is corp on corp crime, they think it's okay.

    Like

  31. Lms, just out of curiosity, were you prescribed Neurontin?

    Like

  32. McWing, I don't remember the name of it, but it sounds slightly familiar. I was supposed to take 1/2 every other day for a week, then 1/2 every day for a week, and then 1 a day. The side effects listed were horrendous and I don't typically do well with quite a few medications so I decided to pass. Seriously, when I broke my foot so bad, I had projectile vomiting with 1/2 of a vicodin and two tylenol pm's cause me to sleep walk, lol. I had such a bad reaction when they tried the epidural steroid injection they canceled the other two. I'm a mess, good thing I don't get sick very often.

    Like

  33. qbso I don't exactly love the insurance companiesIt only took a little over two years and we finally found something in common.

    Like

  34. I have only had minimal experience in dealing with the FDA and Pharmaceuticals and most of my knowledge is surface level, but I have gotten the impression that the PhRMA regs were mostly a result of FDA and government threats. It is a really interesting area of law and from a political perspective as well. In this limited discussion we've already touched on corp on copr crime, government regs seeming to be arbitrary, government regs possibly prevent patients from having access to life saving drugs. Thanks for a good discussion.

    Like

  35. Lms, it's a neuro modulator and was sold by Pfizer for virtually disease. They ended up getting nailed by the FDA for off label promotions and paid the largest fine up till now, 1/2 billion. GSK just agreed to pay 3 billion on Avandia issues.

    Like

  36. Troll:Famvir — you worked for Novartis? I almost took a job with them a few years ago. With NIAID funding levels at 8%, I'm kind of regretting that decision right now …

    Like

  37. Get better 12BB. I am pulling for you.

    Like

  38. That is terrible news and my thoughts and prayers go out to 12BarBlues. I hope she recovers quickly and fully.

    Like

  39. Mike, you're with NIAID? Or you do research funded by NIAID? You said "funding levels at 8%"; what does that mean in your world? Sorry about all the questions but it's interesting to me.

    Like

  40. And good grief . . . all my best to 12BB. I have thought about you often.

    Like

  41. Mike,I worked for SmithKlineBeecham, prior to and after the Glaxo merger. Because Glaxo had acyclovir, they had to sell either Famvir or Acyclovir. Acyclovir had more sales so….I always thought Famvir had better data and was a better drug.

    Like

  42. And good evening, Mr. Troll. I had no idea you were in the pharm biz in any way. Nice to know.

    Like

  43. I don't know the circumstances here, but it would be ironic and a little crazy if Avastin not being authorized for use for breast cancer mets means it's available to someone to try when the proven treatments aren't. I never thought single payer was possible in our political environment, but this sort of thing shows the need for it or something like it. Otherwise, it's just the luck of the draw.

    Like

  44. ABC, I feel terrible because I know 12Bar worried so much about her insurance coverage. We used to joke with each other about trying to last until Medicare age. When ACA passed and they started the pre-existing conditions coverage here in CA, we finally helped our daughter get on it and she asked me a lot of questions about it. It's pretty unaffordable though if you're older. We ended up splitting it with our daughter because even at 32 she couldn't do it on her own, but I had a hell of a time talking her into it. 12Bar ended up with only major medical and she was never sure going in what it would really cover or for how long. So yeah, we still have a long ways to go to fix the health care system.

    Like

  45. I'm sorry to hear about 12Bar. I've enjoyed her comments over the years and wish the best of luck for her. BB

    Like

  46. I don't know the circumstances here, but it would be ironic and a little crazy if Avastin not being authorized for use for breast cancer mets means it's available to someone to try when the proven treatments aren't. I never thought single payer was possible in our political environment, but this sort of thing shows the need for it or something like it. Otherwise, it's just the luck of the draw.I'm not sure I follow the first part of this, but to me the lesson, if there is one, is exactly the opposite. Single payer means the payer–the government–will make all of these decisions for everyone. With a private, free market, you can choose or at least should be allowed to choose, coverage you think best. So you might want to buy insurance from an insurer who has liberal coverage for treatments with questionable efficacy or off-label uses. With government in charge, that all goes away. This was Sarah Palin's point; it certainly was not original to her, but it is correct, unless you think the government will and can just pay for everything.

    Like

  47. okiegirl:I'm funded by NIAID. Yes, I'm on the government dole. "8% funding" means that you have to score in the 8th percentile on your grant submission in order to get funding. Functionally, about 15% of all NIH grants have been getting funded. But some institutes have been hit harder than others. For one review panel that I know about (for NHLBI), only 3 out of 85 grants got funded. The National Cancer Institute funding level is at 6 percentile right now, even with cuts to intramural funding that Varmus has made to be able to fund more extramural grants. It's an uneasy time being an academic researcher right now. If I don't get another grant soon, I'm going to be looking for work somewhere else.

    Like

  48. Mike, thanks . . . and good luck. Thought that might be what you meant on the 8%. I work with academic researchers in another healthcare area (edit, finalize and assemble our grant submissions and manage some funded grants). We too are sweating out NIH grant funding but I'm not sure what percentage in our area is right now. We are in our last year of funding on 4 of our largest federally funded grants. I expect to be absolutely pounded in January in order to make February submission deadlines because everybody is planning to submit.

    Like

  49. Thanks, okiegirl. Sounds like your job is to keep us researchers from screwing up too much on our grant submissions. Your sisters at Penn State and USF have done a wonderful job for me in making sure that all those darn forms are properly uploaded onto grants.gov. Without people like you, we don't get our grants.

    Like

Be kind, show respect, and all will be right with the world.

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: