"Just when I thought I was out, they pull me back in."
I know I've used that quote before several times over the 9+ years that I've been blogging. These days, I probably use it most frequently when it comes to the topic of Stanislaw Burzynski. Every time I think that I can give the topic a rest for a while (and, believe me, I do want to give it a rest), something invariably seems to happen to pull me back in. So it was yesterday when i was made aware of a new development so disappointing that I'm still wiping the dirt off my chin from my jaw dropping to the floor. Even more amazing is that my disappointment stems from my perception of cynicism that actually was not Burzynski's, but rather by the FDA in response to Burzynski's cynical use of cancer patients as shields and weapons against the FDA that has led those of us who support science-based medicine to be subjected to criticism from the families of patients with cancer, who have been erroneously convinced that Stanislaw Burzynski is their loved ones' last chance to survive. Actually, I can't tell if it's a cynical move or a breathtakingly naive move, but it's a huge mistake regardless, as you'll see. I'm guessing that some of you will think of it as a very clever move, and so it is, but it's a cleverness we could use less of.
For those of you not familiar (I know regular readers are and that my summaries in each post about Burzynski can get repetitive, but I live in hope that new readers will read this and be informed about what Stanislaw Burzynski is really all about), Stanislaw Burzynski is a self-proclaimed cancer doctor in Houston—he has no training in oncology and hasn't even passed his boards in internal medicine—who in the 1970s claimed to have discovered endogenous cancer fighting chemicals in human blood and urine that he dubbed "antineoplastons" (ANPs) while working as a researcher at Baylor. Unfortunately, he soon became convinced that only he could develop them into an effective chemotherapy drug and left Baylor to administer ANPs to his own cancer patients. Patients flocked to him because he claimed to be able to cure cancers that conventional medicine can't cure. This led to a series of battles between Burzynski and various authorities, including the Texas Medical Board, the FDA, and various attorneys general, because of his use of ANPs, which are not and never have been FDA approved, as well as for various—shall we say?—issues with insurance companies. Ultimately, in the 1990s Burzynski beat the rap and effectively neutered the FDA's case against him by submitting dozens of clinical trials to the FDA for approval, which, given how much pressure the FDA was under from Burzynski's friends in high places (like Texas Representative Joe Barton), the FDA ended up approving. However, as Burzynski's lawyer himself bragged, these clinical trials were shams designed to allow Burzynski to keep treating cancer patients, not clinical trials designed to produce any real evidence of efficacy. Not surprisingly, although Burzynski has published the odd case report or tiny case series, he has not yet published the full results of even a single one of his many phase II trials. There is, quite simply, no convincing evidence that ANPs have significant antitumor activity in vivo in humans, even after 37 years.
Most recently, Burzynski was once again investigated by the FDA about a year ago. Because of the death of a patient due to hypernatremia (elevated sodium level) due to ANPs in 2012, the FDA put a partial clinical hold on his pediatric clinical trials and extended it to all of his clinical trials. What this means is that, although Burzynski can continue to treat patients who are already in his clinical trials, he can't enroll any new patients in them. Of course, one of the big issues with Burzynski that contributed to his problems is that he abused the FDA process known as the single patient IND, which is more commonly known as the compassionate use exemption. These are special case exemptions in which a single patient is allowed access to an investigational agent outside the auspices of the clinical trial. Indeed, when the FDA slapped him down most recently, in December, one of its findings was just that: Burzynski abused the single patient IND process and his institutional review board (IRB), the committee that's supposed to oversee clinical trials and safeguard the interests and safety of clinical trial subjects, played fast and loose with the rules.
Since the appearance of a USA Today story by Liz Szabo spelling out all of these issues, Burzynski has been frantically trying to save his empire. Whether "encouraged" by Burzynski or just by one of the patient groups that have become true believers, patients with deadly cancer have been starting petitions, pressuring legislators to intercede on their behalf to the FDA, and paint Burzynski's ANPs as their only hope of survival. I have no doubt that these patients believe it, but they have the potential to inadvertently do great mischief to the law, either through their use of their tragic stories to promote misguided "right to try" laws or through their use of patient stories to pressure the FDA to loosen protections on human subjects in clinical trials. Perhaps the most tragic story is that of Rafael Elisha Cohen, a six-year-old child with medullablastoma who is not doing well and whose parents have been at the forefront of pressuring the FDA. As horrible as the Cohens' situation is—and we all understand that it's a horrible, horrible thing to have a child dying of brain cancer—unfortunately, the FDA appears to have decided to cave. The other day, on a Facebook page dedicated to raising money and pressuring the FDA, Devorah Teicher Cohen announced:
UPDATE-
Thanks to everyones hard work the FDA did end up approving the Antineoplastins for compassionate use - they do not let Dr B administer it.
The condition is, if an oncologist request this protocol FDA will issue compassionate use within 24 Hours.
FDA recognizes the data of those who survived aggressive brain tumors due to the ANP and is therefor after a long and cruel wasting TIME period allowing it. There are currently 8 pediatric patients that need this medicine NOW!!!!
Refael Elisha can not travel at this point...so we would need an oncologist in the NY area... we are in touch with other kids that are ready to get on a plain if they get the signal of a cooperating oncologist.
It is beyond words to express our sadness that FDA ended approving the drug but Elisha is in critical condition at the moment.
We are not holding our breath and are trying different alternatives , If HASHEM wills it we will get the medicine but if not, that is from Hashem for the good. in the meantime Please put your fillers out there and message me in privet if you have any leads , even if not in NY it might work out for the other desperate children.
im copying the announcement from ANP site
Wanted: One brave courageous oncologist or oncologists willing to examine and treat up to eight pediatric brain cancer patients who have run out of treatment options and now require a Compassionate Use IND Emergency Treatment protocol from the U.S. Food and Drug Administration. The ANP Coalition needs your help now. Please visit www.anpcoalition.org or call (925) 699-9116. Thank You
Can anyone figure out why I can't make up my mind whether this decision, if what the Cohens say is true, is stunningly cynical or stunningly naive on the part of the FDA? Instead of standing firm for science and gently continuing to point out that it can't allow any more single patient INDs for ANPs be approved based on science, Burzynski's past violations, and the need to protect vulnerable cancer patients, instead the FDA has apparently dangled the false hope of a single-patient IND in front of Elisha's family (and the eight other children petitioning for such INDs), likely knowing full well that it is incredibly unlikely that any reputable pediatric oncologist would agree to administer ANPs, given Burzynski's reputation. In a way, what the FDA is doing inadvertently compounds the family's agony. Now they have false hope again, except that this time it's doubly false: False because, based on existing evidence and what we know now, ANPs almost certainly don't work and false because of how incredibly unlikely it is that any pediatric oncologist will take on such a patient and administer ANPs, given Burzynski's history, the utter lack of supporting science for the efficacy of ANPs, and the amount of work and expense that would be necessary to do so. The families will now be showing up in the offices of pediatric oncologists, begging them to agree to do a single patient IND and administer ANPs to these patients. Ditto some adult oncologists, who will have patients like Liza Covad pressuring them to do the same.
Here's why the FDA's action is doubly cynical (or naive). According to FDA regulations, there are a number of requirements for a single patient IND and several things any physician seeking to administer an investigational agent as a single patient IND must do. Here's the most important one that makes it even more unlikely that any single patient IND will be granted:
5. Informed Consent Statement that states that informed consent and approval of the use by an appropriate Institutional Review Board (IRB) will be obtained prior to initiating treatment. In the case of an emergency, treatment may begin without prior IRB approval, provided the IRB is notified of the emergency treatment within 5 working days of treatment.
See what I mean? Even if a family were to find an oncologist willing to jump through all the hoops to get a patient on a single patient IND to be treated with ANPs, that single patient IND would still have to be approved by the IRB of the institution where that oncologist practices. Sure, the oncologist could declare the treatment an "emergency"—although in none of the cases that I'm aware of other than that of Elisha Cohen could be properly termed an emergency so urgent that the physician couldn't wait a week or two to have the IRB formally approve the IND, even if ANPs actually did have any efficacy—and start treatment pending IRB approval, but as soon as the IRB convened to discuss the IND, very likely the plug would be pulled. No more ANPs. Remember, these would be real IRBs, not Stanislaw Burzynski's sham IRB chaired by an old crony of his.
There's another question to consider. Stanislaw Burzynski offered to treat some of these patients for free, supplying free ANPs and treating them for free. Will he still do so for them if another physician is treating the patient? My guess is that Burzynski will still send the drug free of charge, as he's been trying very hard to use such offers for publicity and to "prove" that he isn't such a greedy guy after all. However, that leaves all the other expenses of treatment, which will not be paid for by insurance because ANPs are not an FDA-approved drug. Who's going to pay for all of that? Sure, some of the families have raised quite a bit of money. Elisha's family, for instance, has raised nearly $150,000. Others aren't so lucky.
Of course, one thing that needs to be emphasized is that this Facebook post is the only evidence out there that the FDA has caved and decided to allow single patient INDs. It is possible that one of the Senators or other legislators did indeed pressure the FDA, leading the relevant enforcement officials to come up with this decision in order to get them off their backs without actually doing anything. They could credibly say, "Hey, we offered compassionate use, but I'm sure you'll agree that, given his history, we can't let Burzynski be the one to administer the ANPs on compassionate use. Look at his history of playing fast and loose with IRBs and not obeying the rules with respect to INDs." This might even sound convincing and seem clever, but, if the FDA really has done this, its consequences are likely to be disastrous. The long-suffering families will have false hope extended to them once again, only to find out that it's a useless offer. In addition to continuing to scramble to raise money, they'll scramble to find oncologists willing to do the not inconsiderable work to get a single patient IND approved and administer ANPs, something few, if any, of them are likely to succeed at doing. The families don't know it yet, but what the FDA has done will only add to their misery. Meanwhile, Burzynski gets a propaganda victory.
If what the Cohens have announced is true, I don't know what the hell the FDA was thinking.
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I disagree. I think the FDA's solution is brilliant. Thanks to this decision, they come out looking like generous good guys - as you yourself put it, they can now say "I’m sure you’ll agree that, given his history, we can’t let Burzynski be the one to administer the ANPs on compassionate use."
Let the families go from one oncologist to another. Let them hear from the experts in person how much proof there is that ANPs don't work. Let them hear the facts from somebody other than Burzynski. This forces the family to do that, maintains the credibility of the FDA as an organization that isn't "beholden to the drug companies" as the conspiracy theories claim, and accomplishes the very important goal of creating a separation in people's minds between the efficacy of a (fake) drug and the smooth-talking, totally honest I promise, doctor that's offering it.
Everything about Burzynski says it's all about the money. It sounds like someone at the FDA agrees with you, Orac--but isn't willing to own the direct responsibility for simply saying "no" to Burzynski's clinical trials--hence this bizarre (if true) FDA decision. If Burzynski's revenue stream comes only from treating patients under the umbrella of "clinical trials", Burzynski has to be feeling the $$$ squeeze by now. I sure hope there are no pediatric oncologists willing to give ANPs to children, but you've already blogged about the woo that's infiltrated at least one nationwide chain of adult cancer treatment centers. What are the reporting requirements for single-patient IND treatments? Since pretty much only Burzynski (or his staff) has been giving ANPs up till now, he's had complete control over charting, diagnosis of complications, coding for billing, and what results/outcomes he releases (rarely) from his trials. He won't have that control (presumably) if a 3rd party is administering his ANPs as described above. That could help expose the fraud that ANPs are. But it's still not the best way to shut down a quack.
@Yerushalmi
On the flip side, all it would take is a few dodgy oncologists and sub-par IRBs to put Burzynski back in business. I imagine that if it meant sharing some percentage of the revenue vs. no revenue at all, he'll make a deal with some unscrupulous docs.
@Todd:
If anything, that's another side benefit: if there are any oncologists out there who are dodgy enough to be willing to give antineoplastons, this announcement will draw them out of hiding. I wouldn't want to find myself getting conventional treatment from a doctor who believes in homeopathy, for instance, because that's a sign his judgment is flawed - but I have no way of knowing if my doctor believes in that or not, since I can't read his mind. So if some oncologist out there does decide to pick up Refael Elisha Cohen's case, that's a huge red flag that all of that oncologist's patients would be glad to find out about, so they can switch doctors.
Plus you can bet the FDA will put them under extra scrutiny.
I wonder, if they indeed find an oncologist to administer the ANPs and the patient died as a result of the treatment... what then?
Hmmmm....so what respectable Oncologist would administer what is effectively an untested treatment on a child?
@Yerushalmi
You have greater faith in the rationality of people facing a devastating prognosis than I do.
@T
Good point. If the patient dies, Burzynski is shielded.
Plus you can bet the FDA will put them under extra scrutiny.
If the FDA were functioning well enough that I would be willing to take that side of the bet, then Burzynski would have long since been forced out of business, at least in the US.
And while the terms of the alleged FDA offer specifically exclude Burzynski himself, I didn't see anything in the report that would exclude a current or former employee of Burzynski's clinic. There may be more to the deal than what the Cohens have posted, or they may be mistaken about a deal--we've only seen the Cohens' side so far--but it looks like the only thing that would prevent a Burzynski associate from administering the drug would be that none of his associates are licensed to practice in NY, NJ, or CT, and that only because the patient can't travel outside the NYC metro area.
Eric -- that was my first thought too. It would not take much creativity for Burzynski to get around that. So he can't administer the drugs himself. All he needs to do is find an MD in sufficiently desperate financial straits to be his patsy. We've certainly seen lots of other frauds do that. Wakefield and the Geiers come to mind.
That said, there is one ray of hope, and that's that if another doctor does start administering ANP, totally apart from Burzynski, for an actually *reasonable* price, perhaps that will run him out of business. Once patients realize these treatments don't actually have to bleed them dry financially, they'll realize his true colors and he'll be finished. And who knows? Maybe somebody with an actual heart will properly study the things and publish their results.
...except, unfortunately that the results would almost certainly show ANPs are worthless for cancer treatment and a 2nd group of patients would have had to have been tested thanks to Burzynski's ability to dodge accountability for presenting results of his clinical trials (if he even really did them).
I suspect that would be the case, Chris, but if they actually did the science they'd be light-years ahead of where the monstrous charlatan Burzynski is. And then maybe we could finally put this nonsense to rest.
Maybe somebody with an actual heart will properly study the things and publish their results.
Not unless they get their IRB to approve the trial, which as Orac points out in the original post is a major stumbling block for any doctor who isn't already a Burzynski affiliate. I'm sure there have been other IRBs out there which are comparable to Burzynski's in dubious conflicts, but that kind of thing tends to draw FDA scrutiny (indeed, it's one of the sources of Dr. B's current troubles with the FDA). A halfway reasonable IRB would reject the study because there is reason to believe that ANPs are not just useless as a treatment but actually harmful.
@Eric Lund
Whether an IRB would approve it or not would largely depend on a) how knowledgeable the members were about ANPs and Burzynski and b) what information was submitted.
Having served on an IRB, I could see one being gulled by a clever doc. Especially if it's a very busy IRB, where the members wouldn't have time to look at resources outside of the submitted materials.
This is going to go badly for our cause. It's so frustrating to see the FDA behave passive aggressively here. Someone give the FDA some teeth!
Burzynski's camp will spin this to something along the lines of "See? The FDA is blocking life saving medication for children by setting up all these hoops to jump through. They know the ANPs work or why would they approve the compassionate use? But they have it out for ME and won't let me administer treatment. Now someone is dead."
And he won't hesitate to march the poor families of these suffering children to the camera. What a nightmare.
Yes, now Burzynski has the escape clause of "The FDA has it in for me and it was their delays that killed these patients." I expect the next one, should no physician or IRB accept this treatment, to be claimed as evidence of FDA intimidation or conspiring against his "cure."
Yes, I can see the propaganda now: "The FDA acknowledges that ANPs are effective against cancer but, because they have it in for me personally, won't let me save these children."
Lets not forget that these patients really don't have any other options. Provided they get a legitimate informed consent, then I would not object to them entering a trial. Thanks to Stan "I never published data" Burzynski, we really have very limited data on what ANPs do as far as side effects and effects on tumors. I'm sure Orac could argue that what we have is enough to reject ANP at this time, but I haven't heard anyone claim there is zero chance they work.
Don't get me wrong. SB is a fraud and I think the chance these drugs do anything except cause serious side effect is next to zero, but the only way to move forward in these devastating untreatable diseases is to keep taking those long shots. And there necessarily needs to be patients willing, with a full understanding of the low probability of success, to undergo treatment. Don't forget that proving something is not useful is still a step forward.
Just playing devil's advocate. I'm sure there are 100 experimental long shots that have better odds than ANP.
I'm very afraid that history will repeat itself because this situation has some similarities to the tragic story of Joey Hofbauer, whose parents were able to find a quack doctor to administer the the toxic and ineffective Laetrile.
Here are articles from the 90s about Burzynski and antineoplastons- How is this still going on?
http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/burzynski2.html
http://www.nytimes.com/1996/07/24/us/to-the-hopeless-a-cancer-cure-beck…
http://articles.courant.com/1997-01-12/news/9701120070_1_brain-tumor-st…
As others have pointed out here, the drug itself is available because it is used for disorders of the urea cycle. One internet site mentions that it can be bought in bulk for $850 per kilogram. There seems to be no reason that somebody couldn't set up a clinic outside of US jurisdiction and pump the stuff into people who really want it. That suggests to me that patients and parents of patients are looking more to the magical qualities of the Burzynski name than the possible utility of the drug itself. Otherwise, why haven't they gone somewhere to get the treatment? Is there nobody in one of the quack cancer clinics that is willing to offer this service? I would suspect that a country that is willing to allow fake stem cell injections into the spine or the use of Laetrile would also allow the infusion of sodium phenylbutyric acid.
If the FDA is actually willing to grant permission for individual trials, provided that some legitimate oncologist is willing to do them, then perhaps we will finally get a real clinical trial with published data, and the rational world can put this question to rest. I understand that Burzynski and his followers will continue to complain, but that would be the case anyway.
I think it is possible to consider the Burzynski saga in a different way. If some clinical trials are carried out by honest people, and if they are the abject failures that we expect, then that will be that. Burzynski will of course complain that the trials were done wrong (as he has complained in the past). And if they work at any level, Burzynski will be revealed as a really lousy scientist, since he had it within his power to prove that his medicine works, and he did not. If the treatment is a complete failure, Burzynski would be left with an argument that only he is actually capable of doing the job right, which is not a very convincing argument except to the magical thinkers. And they are going to continue to be magical thinkers anyway.
One other thought for the more organic chemistry minded here: Is there any modification of the structure that would provide the effects of phenylacetate without requiring the use of the sodium form? It seems to me that Burzynski has had lots of time to think about the problem, but doesn't seem to have tried anything new since 1977.
Isn't the kind of trial they're talking about a single patient "compassionate use" trial? The FDA doesn't call them compassionate use--they're Expanded Access Programs--but wouldn't the data from one patient be meaningless? The EAP's are treatment trials, not research.
@ Enzo, #15
I don't think FDA is lacking teeth. I think the body part it's missing is the spine.
I would gather that Burzynski already has a few Oncologists on speed dial for such an occurance. Also does the oncologist and treatment have to be done in this country?
Do they have to be oncologists? Perhaps Mark Geier would be interested. Sadly, I'm not joking.
Why didn't Dr. B take his ANP offshore a long time ago?
Bob G:
I think you are referencing sodium phenylbutyrate, which is an FDA approved orphan drug for treatment of urea cycle drugs. Orac describes how Burzynski prescribes phenylbutyrate off-label as part of his very expensive (e.g. 100k/month) “personalized gene-targeted cancer therapy”.
As Orac notes, "Dr. Burzynski’s rationale for using phenylbutyrate, namely that it’s a prodrug for antineoplastons, while technically true, is deceptive. The reason is that pharmacokinetic studies suggest that phenylbutyrate does not generate clinically useful concentrations of phenylacetate in the blood. Also, as we have seen, the NCI’s concerns were not without foundation, particularly its concern about the risk of severe hypernatremia, which several of Dr. Burzynski’s patients have experienced."
He cites a phase 1 study which concludes:
Antineoplastons have undergone enough testing over the decades. There is no reason to subject another innocent child to the potentially deadline effects of a drug that cannot affect cancer any better than conventional care.
As for your final question, I am not a chemist so do not know how one would remove the sodium from sodium phenylbutyrate. But all this is tooth fairy science because there is no evidence that phenylbutyrate can help Raphael Elisha or any other child for which the FDA is apparently granting permission for expanded access.
There was an unconfirmed report that Raphael Elisha Cohen has already received phenylbutyrate but had a bad reaction to it. If he did receive phenylbutyrate, then the experience does not bode well for a future treatment with with ANP.
Operating in the US gives SB the veneer of legitimacy that a clunic in Tijuana would not.
So, if you want to make an impact, I'd go ahead and complain about Burzynski to: Dana.Walters@fda.hhs.gov Ask why they are not taking action decisive against this wretched place.
Johanna: Indeed, several potential Burzynski patients have turned to the Gerson clinic in Tijuana. It seems that many who turn toward one quack treatment will turn to other quack treatments like Gerson Therapy.
Here is one patient who balked at the $100k/month that the Burzynski Clinic wanted but is now going to try the cheaper option at Gerson.
If Burzynski really did have a miracle cure for so many diseases, he would be a pretty awful person to withhold his treatments from so many instead of publishing his trial results and getting approval by the FDA and insurance companies.
Unless I'm completely misleading their regulations and guidance, it looks to me like they simply don't have a (legal) reason to say no, assuming the treatment is with antineoplastons A10 and/or AS2-1, which are designated orphan drugs.
I'm also assuming that the five criteria listed in the guidance rundown on IND exemptions for lawfully marketed drugs or biological products for the treatment of cancer would be met by this case. But it looks like they would be.
If so, I don't think they have grounds for saying no.
Even if not, my guess is that they got outlawyered somehow and this is the upshot. It just has that feel.
I mean "misreading" not "misleading,"
V. Freudian.
I left out my main assumption. To wit:
The idea originated with (counsel for) the patient's family, not with the FDA or Burzynski.
Bob, can you tell us a bit more about dana, walters before we write?
Although I think I can see a way it might be part of Burzynski's strategy, too.
It would be super-cynical and, in fact, evil. But that's not a rule-out.
I guess it might be the first in a series, either way, though, assuming a legal loophole has been found.
Maybe I'm wrong about that, however. .
the FDA search shows A10 not approved.
http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm
Is there another reliable source that says it is? I found a reuters press release-type article 12/2/2008 but if it were correct, something should have been in that FDA list, shouldn't it?
It's not clear to me whether any of the other MDs on staff at the clinic are (certified) oncologists. One of them is "specialist certified." But the phrasing is ambiguous.
Does anyone know what the what is with that? Now or historically?
This is what she does. http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/…
@mho --
A reliable source? No. The press looks like it all comes from Burzynski.
But there are clinic promotional materials -- which, fwiw, are posted on the FDA's website in the "warning letters/enforcement actions" section -- according to which A10 and AS2-1 were designated orphan drugs for brainstem gliomas in September 2004.and extended to all gliomas in 2008.
Seems unlikely that BRI would risk erring on such a point, since it also files with the SEC, which would frown on that kind of misstatement.
You never know, though.
And they were designated, but were not approved.
I don't know what that means. I just can't see why the FDA would do this unless they had to.
I imagine/think/hope that Burzynski's too much of a potential political risk to be worth an expenditure of legislative clout these days.
No. Sodium phenylbutyrate (which Scamislaw touts as being an antineoplastinoid "prodrug" for the "gene-targeted therapy" side business) is an orphan drug.
^ Perhaps I'm mistaken. It appears that Burzynski has twice announced (in 2004 and 2008) that "Astugenal" and "Astenegal" have been granted OD status. This of course depends on expiration of the patents.
The best realistic outcome would be if the parents looked around for reputable oncologists, who patiently and compassionately explained why Burzynski's magic potion is bunk, and convinced them to use whatever real SBM options remained (or if it's too late for that, go to palliative care mode for patient quality of life).
To the extent that some of these parents relentlessly cling to false hopes for ANPs, accept the fact that nothing can persuade them otherwise, and the outcomes for their children will be tragic.
Realistically, seek whatever good can be salvaged from the tragic outcomes, such as data that can be used to conclusively shut down the whole ANP scam and ideally put Burzynski out of business permanently.
The fact that Burzynski can wring 100,000 dollars per month out of people who are desperate, demonstrates that he is either a full-fledged psychopath, or that he is thoroughly delusional about his quackery. Each of those types is equally dangerous.
@Narad --
The status of both is that they're designated orphan drugs.
Says so right here:
http://www.accessdata.fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cf…
It also says they're "not FDA approved for Orphan indication."
But I believe that just means they're not approved for a specific indication by the FDA -- ie, they're investigational.
I guess it's possible that the FDA has agreed to let Burzynski's sponsorship....No, that doesn't make sense.
Anyway. That's the status.
My completely uninformed, shot-in-the-dark legal reasoning is that since Burzynski was shut down for the shortcomings of BRI, not the shortcomings of ANPs, the FDA has no cause to deny another physician to use them on the same or similar terms that Burzynski did.
Because they (ANPs) are exactly the same drugs they've always been. No more and no less is known about them. So if they were okay then, they should be okay now.
Confirmation of what has happened:
http://www.usatoday.com/story/news/nation/2014/03/21/burzynski-cancer-p…
That's interesting. One immediate upshot of there not being an indication seems to be that anybody else could do the same thing with the same stuff.
OK, maybe I should have properly figured all of this out long ago. The only benefit to an orphan designation is 7 years' exclusivity after marketing approval (unless you're gouging Medicaid for colchicine, in which case there's a three-year bone tossed for sunk costs, or something; it's starting to come back to me).
In the fanciful scenario in which anybody but Burzynski can demonstrate effectiveness, that period of exclusivity is more or less theirs for the taking.
It seems that the move by the FDA takes the politicians right out of it.
So, if i'm reading Szabo's article correctly, Buryzinski's the one supplying the meds? That makes no sense - he'll be off the hook medically while still profiting financially. Very frustrating.
According to the article, "Burzynski will supply antineoplastons for free, says his attorney, Richard Jaffe."
Of course, we don't know what he'll charge as "case management" fees.
@Narad --
Right. But the logical implication of that is that it can't be marketed but can be used, as long as its use conforms to the criteria it was designated for, by a doctor/institution that complies with all the regulations and guidelines. Right?
As I understand it, assuming standard treatment options have been exhausted, if those conditions have been met, the FDA actually doesn't have regulatory authority to refuse compassionate use unless the risk has been demonstrated to outweigh the (putative) potential benefit.
And as I also understand it, the risk is toxicity. But that's a risk with chemo. So in order to refuse compassionate use they'd have to prove a negative (ie -- that it definitely doesn't work.)
So I think they're just stuck, atm. They can block Burzynski, but not ANPs.
It's not like Burzynski is the only source of USP-grade phenylbutyrate or phenylacetate nor the only source of information about their clinical trials. The former (PB) is an approved drug for a urea cycle disease (as mentioned above). I found info about PB online at Memorial Sloan Kettering's website. That site's page lists several references for it's off-label use, but the latest one for cancer is from 2009, and is clearly a negative result. Why people (esp those who are not desperate cancer patients) can't see through Burzynski's lies is a mystery to me. If these orphan drugs were so amazingly effective, then dozens of oncologists would have replicated SB's work over the last 30+ years.
I can't help thinking that the FDA has, what we used to phrase, 'Sloped Shoulders'.
What I mean by that is they're unwilling to take the crap for any decision they make so they pass it on to someone else.
It's unclear to me that this is related to the OD designation, but unwinding the Code of Federal Regulations is something that I'm not always up to.
This is 21 C.F.R. § 312.310. "FDA may permit" doesn't sound like an obligation, but as above, it would require quite a bit of digging to sort out whether courts have construed the section as such.
True.
And even then, there's usually only one attorney in the world -- probably somewhere in Maryland -- who actually understands what the law is, in my experience of such things.
Maybe the ANP Coalition hired him or her.
Ann: Since I first heard about Burzynski a few months ago, I am continually surprised at the new and crazy things that I learn about the situation. Read some of the shocking stories here, or the links that I posted in comment 19 from the 90s: https://theotherburzynskipatientgroup.wordpress.com/
It is tragic because these families have been told the worst news imaginable and Burzynski swoops in and says that he can save them. They spend all their savings and the donations of well-meaning friends. If they don't happen to live very long, Burzynski blames anyone but himself.
The lobbyist for the ANP Coalition is already spinning Refael Elisha Cohen's story so in the event that he passes from this world, the FDA will be blamed for not allowing the "miracle cure" until it was too late.
And you can see from the USA Today article, there are former clients of Burzynski whose ANP-treated kids died but still think ANP might work for others.
@BobG
Sodium phenylbutyrate is a simple salt, so in principle you could replace the sodium with just about any counterion you could imagine. However, given the insane doses of phenylbutyrate given, I imagine that whatever counterion you might choose, no matter how ordinarily innocuous it might be, you'd probably end up giving an overdose of it.
Looks like esterification is a possibility.
The FDA under David Kessler would have never done this!!
A bit off-topic, but I got a petition email today about this case.
The patient (Ray) has adenoid cystic carcinoma and has been taking votrient (pazopanib) and apparently responding.
http://www.gofundme.com/Rays-Cancer-Battle
Apparently it's approved for soft tissue carcinomas, sometimes as a second option when primary treatments have failed. Also, it seems to have nasty side effects. (Wear gloves so you don't actual touch your feces!)
Anyway, does anyone know anything about this usage?
Wow, I googled the number for the ANP Coalition and it's just down the street in Clayton, CA. Who knew such a small town could be a hotbed of Woo.
That's Ric Schiff.
DrDuran @ 60:
If the ANP Coalition is local to you, that means you have potentially many opportunities to observe these people in various contexts.
Never miss a 'learning opportunity,' and I'm sure we'd all be interested to find out whatever you might happen to learn.
@Narad et al
Sure, esterification would be one way to block the carboxylic acid end of what is, after all, a modified fatty acid, and this would replace the sodium in what is, after all, just a sodium salt of this modified fatty acid. Using glycerol to esterify PB just creates a slightly modified monoglyceride. Why not go a step further and put PB into a diglyceride or triglyceride? The effect would probably be the same.
It's curious that Stanislaw never quite got to the chemical identification of his material until it was quite a few years later. Maybe he never really figured it out until somebody else told him. I'm not enough of a historian of Stan to really know the details. What becomes obvious though is that in failing to understand the simple chemistry of his miracle substance, Stan was not in a position to do a little chemical tinkering in order to develop a compound with the same pharmaceutical effects (whatever those might be) while sparing the patients the peril of a lethal salt dose.
Like I've said, he's at best a lousy scientist. He more or less isolated some stuff that is less prevalent in some cancer patients, made a wild hypothesis that the difference was causal rather than some secondary metabolic effect, and started pumping it into patients. What he was missing was some sort of tissue culture assay or animal assay for an anticancer effect, so the road to improvements on the stuff was blocked for him. Meanwhile, he seems to have failed at demonstrating the merit of his wild hypothesis.
His next problem was that when he found out (if he has ever accepted the idea deep down) that his "antineoplaston" is really Phenylacetate or phenylbutyrate, it was already too late for him, because lots of other people -- real scientists -- were playing with PB and modified PB as therapy for various things. It's also curious that in the various papers that report on studies of PB and PA, there don't seem to be references to anything Stan has done. Even if he were a grade A jerk, if he had done any real science it would get cited in one of these papers.
By the way, there's a caution in that PB esterification study that kind of jumps out at you. At the time of that publication, PB was being tried as a treatment for sickle cell disease due to its ability to promote the production of fetal globin. That's a pretty serious effect, considering that fetal globin is mostly shut off after birth. This suggests that PB has some potentially radical effects on gene expression, and not all of them are likely to be beneficial. The induction of genes that should ordinarily be switched off is one of the characteristics of cancer cells. Alternatively, it would be amusing if PB stimulates the particular microRNA that induces the stem cell state.
The triple was tried:
"Based on the AUCs for PB, the bioavailability of the glycerol monoester or triester are about 63 and 42%, respectively, of that of the sodium salt. However, the bioavailability of the glycerol-mono-PB ester is not significantly different from that of the sodium salt. The bioavailability of the glycerol-tri-PB ester is significantly lower than that of the sodium salt."
The original hypothesis was "antineoplaston deficiency". The Japanese contingent is still coughing this one up.
You guys are all bankrolled by the pharmaceutical industry. You claim this guy is all about the money but so is your industry. And I don't believe Dr. Burzynski to be. At this point all you can hope to accomplish is to slow the knowledge and subsequent public availability of ANP long enough for the industry to adapt so it doesn't collapse or better yet, steal his proprietary property. The US govt and NCI already tried once and failed. Chemo and radiation kill people every day! Yet you stopped his trials because a boy died of electrolyte imbalance? It is sad but the traditional methods kill many more, irrespective of whether we look at totals or proportions. You claim he hasn't completed phase III trials but no peer reviewed journal will let him publish the results. If people are going to die anyway, they should be allowed to make their own informed decisions.
@ John Taylor
Ever seen a picture of the house Dr. Burzynski bought?
Not about the money?
Let him prove his anti-plastons work. But he doesn't. He just lures vunerable people in, by telling them, he can cure them. To me he is just a greedy bastard.
There's nothing proprietary left. Anybody could administer mixtures of PA and PAG. Nobody's bothering.
He never even started the one Phase III trial. If you mean the Phase II trials, nothing is stopping him from making public the manuscripts and the rejection letters.
all bankrolled by the pharmaceutical industry
When did this become the standard cacophemism for "can be bothered looking up the facts"?
...because it is hard to argue with someone -- even if only a drive-by commenter in this case -- who takes it as axiomatic that to display any knowledge of the topic in question is to betray oneself as a paid employee of a vast conspiracy.
Mr. Taylor: "You guys are all bankrolled by the pharmaceutical industry. "
That is a pretty interesting defense of a guy who runs a factory to make ANP, a pharmaceutical, and requires his patients to buy it from the pharmacy that he owns (at inflated prices).
So, is it "Big Pharma bad", but "Con man who makes pharmaceuticals good"?
a guy who runs a factory to make ANP, a pharmaceutical, and requires his patients to buy it from the pharmacy that he owns (at inflated prices).
Burzynski used to make his own chemicals but these days I believe he buys them wholesale from pharmaceutical warehouses. "Requires his patients to buy it from the pharmacy that he owns (at inflated prices)" is still true, however.
He doesn't equip his patients with the Hickman catheter for drug administration, either; they're sent to a private hospital for that (with a separate item on their bill). And now that he's realised that patients can administer the chemo themselves and monitor their own condition, he sends them home to do that, thereby saving on nursing staff. In short, it is not at all clear to me what service he provides to his customers, other than to alleviate them of wallet congestion.
I'm not.
It's not my industry. I agree that it's distinguished by soulless greed. But that doesn't excuse Burzynski.
Oh no?
On what do you base that belief?
The only person who could possibly speed or slow the knowledge and public availability of ANPs is Burzynski.
He's had decades to get the job done, during the bulk of which he wasn't being prosecuted or interfered with by anyone at all.
They also save many lives.
Did not.
The FDA stopped his trials because multiple patients had severe toxic reactions and he continued to treat them. Among other things. The destruction of records and 102 overdoses are also mentioned.
No. Based on what's in the public record, if you look at proportions, it's hard to get more fatal than being treated by Burzynski is. Actually.
He should self-publish then. It's unconscionable that he doesn't. The internet's right there. And it's a matter of life and death, ostensibly.
I agree.
This is not about them.
If doctors are going to practice, they should abide by the same rules as all other doctors when it comes to stuff like not destroying records and/or avoiding overdoses.