Stanislaw Burzynski and "clarity" from the FDA

I've been writing about Stanislaw Burzynski again, just yesterday having mentioned a warning letter that the Burzynski Clinic received from the FDA last month. Given Dr. Burzynski's history of promoting a highly dubious cancer therapy that he calls antineoplastons and administering them to patients under the guise of clinical trials for which he charges patients huge sums of money and of also selling an equally dubious form of "personalized gene targeted cancer therapy" that I've referred to as "personalized cancer therapy for dummies," I took a very dim view of his having received yet another warning from the FDA, to the point that I wondered once again how this guy gets away with it. The FDA is normally so hard-ass when it comes to overseeing clinical trials, not green-lighting phase 3 trials without a solid base of evidence suggesting efficacy in phase 1 and 2 trials. Yet somehow Burzynski, whose evidence base supporting the efficacy and safety of his antineoplastons is thin gruel indeed, manages to get phase 2 after phase 2 trial approved and even a phase 3 trial. True, the trial, having been approved well over two years ago, is still not open to accrual (a story whose details I'd love to find out), but it's there, and Burzynski fans use it as "evidence" that the FDA must think there's something to his treatments.

That's why I had to pause a minute when I came across a post by Catherine Shaffer over at Bioworld, which bills itself as the "daily pharmaceutical news source," entitled FDA’s Confusing Action Against Burzynski – What Does it Really Mean? Shaffer has obviously seen the same warning letter to the Burzynski Clinic that I have, not to mention several other bloggers, and, from the point of view of someone who reports on pharma issues, she is obviously puzzled. She sees the FDA's action as symptomatic of a lack of clarity over what, exactly, constitutes a "promotional claim":

While the OPDP’s move is a welcome step in shutting down Burzynski’s clinical trial pyramid scheme, in which, according to some patient fundraising blogs, trial participants pay more than $100,000 to become guinea pigs for antineoplaston therapy, the letter provides little clarity regarding what is or is not a promotional claim.

The letter specifies, “This provision is not intended to restrict the full exchange of scientific information concerning the drug, including dissemination of scientific findings in scientific or lay media. Rather, its intent is to restrict promotional claims of safety or effectiveness of the drug for a use for which it is under investigation and to preclude commercialization of the drug before it is approved for commercial distribution.”

However, some of the so-called violations strongly resemble claims made in countless biotech and pharma press releases posted on company websites.

As I mentioned yesterday, the FDA letter warned Burzynski that his advertisements on his website violate the Federal Food, Drug, and Cosmetic Act, specifically FDA regulations 21 CFR 312.7(a). These are regulations that prohibit a sponsor or investigator from representing an investigational drug in a promotional context as safe and effective while it is still under investigation. This particular regulation also prohibits commercial marketing or test marketing of an investigational drug and prolonging a trial after the results of the investigation are enough to support a marketing application. Of course, I could never figure out how Burzynski is not charged with violating the part of the regulation that prohibits commercial marketing of an investigational drug. I realize that he enrolls all of his patients in one of his dubious clinical trials (and charges them enormous amounts of money for the honor), but he really does appear to skirt the line and go beyond it when he makes claims for his antineoplastons.

My musings on how Burzynski gets away with what he gets away with aside, believe it or not, not long after I wrote yesterday's post, a fleeting thought crossed my mind wondering how Burzynski's claims on his website (which are now largely gone, obviously having been yanked by Burzynski in response to the FDA letter) compare to claims found on the websites of pharmaceutical and biotech companies. In particular, Shaffer wonders about a statement like this:

"ANP [antineoplastons] was well tolerated with easy manageable side effects of fatigue, skin rash, and electrolyte abnormalities and no chronic toxicities . . . These results compared favorably to radiation therapy and chemotherapy (Mandell, et al. 1999, 7 percent overall survival at 2 years and 0 percent at 5 years), but should be confirmed in phase III trials scheduled to begin in 2009."

Shaffer does have a point in that the definition of what is considered "promotion" of an investigational new drug is rather vague. In fact, it's more than vague; it's more or less undefined. I also actually agree that this particular quote seems to be not particularly hyperbolic or objectionable as far as promotional statements on pharmaceutical websites go; that is, if you don't know Burzynski's background and just how bad the scientific studies he marshals to support his antineoplastons and take his papers' findings at face value.

Shaffer seems to recognize this and even suggests that the totality Burzynski's history might well have led to the issuing of this letter:

But again the FDA’s communication falls short of total clarity as to why certain claims violate regulations and others don’t. In the Burzynski case, the clinic’s lack of evidence to back up its claims, and track record of plundering its patients’ retirement funds may contribute to the OPDP’s actions, but nothing in the OPDP letter actually cites false claims or misunderstanding by patients. “The totality of these claims suggest that Antineoplastons, investigational new drugs, are safe and/or effective for the treatment of various types of brain tumors indicated above, when they have not been approved for these uses,” the letter states, suggesting that the only and entire violation by the Burzynski clinic is that it said the words “safe and effective” before the drugs had been approved ‑ words which are ubiquitous in drug company statements regarding clinical trials of unapproved drugs.

I do have to admit that Shaffer has a point, at least insofar as she notices that the FDA letter to Burzynski doesn't explicitly note Burzynski's history of unethical activities and patients who believe that he can save them from terminal cancer. However, I'm not sure I buy her next conclusion, namely that the FDA letter suggests that the only and entire violation is that the Burzynski Clinic used the words "safe and effective" before antineoplastons had been FDA approved. At least, I didn't read the FDA letter as meaning that. I read it as castigating Burzynski for exaggerated claims and claiming that antineoplastons are safe and effective. Still, I can't help but agree that it would have been useful if the FDA had laid out a bit of Burzynski's history as a way of justifying why it has, in essence, zero tolerance for the sort of language Burzynski used in his promotional materials. Moreover, for all the confusion that Shaffer imputes to the FDA's regulations regarding what constitutes "promotion" of investigational drugs, one can't help but note that Burzynski also used testimonials with glowing, near-miraculous results from his antineoplaston therapy and comments attributed to Burzynski that they are very safe.

I can't help but note that the FDA is sending warning letters similar to its letter to the Burzynski Clinic. Indeed, I found out about one recently sent to Genentech. Ironically, I found out about it from a pro-Burzynski source. It seems as though a Burzynski fan (who calls himself, appropriately enough Burzynski Saves) saw what I wrote about the FDA warning letter and decided to Tweet his objection:

GeneTech gets worse letter from FDA than #Burzynski saying they mislead cancer pts but no mention of it? LOL! http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformat…

Burzynski Saves is troll whose head is so far up Burzynski's nether regions that the two of them could share a set of vocal cords. Of course, The more I see Burzynski Saves (which I will now abbreviate, even more appropriately, as BS) in action, the more I wonder if that's more true than just being an amusing way of pointing out just how BS sucks up to Burzynski. BS is so active on Twitter defending Burzynski, I strongly suspect that he's somehow affiliated with the Burzynski Institute or the Burzynski Clinic. Of course, I could be wrong, and BS could just be a fan who's drunk so much of the Burzynski Kool Aid that he's become a true believer wanting to troll the world with the Good News of Burzynski. Whatever the case, I can't ignore something just because the person showing it to me is about as annoying as it gets on Twitter. Well, I could, but I won't.

So I went and read the FDA warning letter to which BS pointed me. Amusingly, I couldn't help but chuckle at how BS misspelled Genentech, but then I went on to look at the letter itself, which is basically an FDA finding that this particular brochure about the cancer drug Tarceva is misleading. The FDA notes that Tarceva is approved for the treatment of locally advanced or metastatic nonsmall cell lung cancer (NSCLC) whose disease has not progressed after four rounds of platinum-based therapy or in NSCLC that has failed a first line chemotherapy regimen and that it can also be used to treat pancreatic cancer in combination with gemcitabine.

The first claim that the FDA doesn't like is that the appearance of a Tarceva-related rash is "associated with a clinical benefit." The FDA states that Genentech grossly overstates the benefit of Tarceva and that the study used to support the above claim about Tarceva doesn't really support it at all. The other objection that the FDA expresses is that it portrays an adverse reaction (the rash) as a a predictor of efficacy. In addition, it is argued that there were several claims that weren't supported by "substantial evidence or substantial clinical experience" and that the promotional material didn't include sufficient data on the risks of the therapy.

So is this sort of thing the same as what Burzynski did? Sort of, but not really. Yes, Genentech's material does appear to go a bit too far in spinning the scientific data and downplaying potential risks, although I admit that I didn't take the time to delve into the several references that support the FDA's charges. No, Burzynski's material is not the same, at least not nearly as much as BS would have you believe and certainly not enough for Shaffer to be justified in seemingly lumping FDA enforcement actions together with routine FDA enforcement actions and warning letters directed at most pharmaceutical companies. Going back to the Genentech letter again, there's a big difference between it and Burzynski. Unlike antineoplastons, Tarceva is already FDA-approved for certain cancers. We know it works for at least some cancers. The question is whether Genentech is claiming more than the data show in its promotional materials for FDA-approved indications for Tarceva and downplaying known risks. The difference, of course, is that Genentech can legally make the claim that Tarceva is safe and effective for certain indications because it's been FDA-approved. It is no longer an investigational drug. In contrast, antineoplastons are still investigational. BS, as usual, is comparing apples and oranges. Moreover, I'm actually happy that the FDA is sending warning letters to pharmaceutical companies for overstating efficacy and safety of FDA-approved drugs in their promotional materials. This is a good thing. We want the FDA to be vigilant and unafraid to challenge even companies like Genentech, which is now owned by pharmaceutical giant Hoffman-LaRoche.

Genentech's violation is not, as BS would lead you to believe, the same thing as what Burzynski did. It's much milder—and, more importantly, the FDA actually called Genentech out for it. BS uses the example in a typical concern trolling fashion in which he tries to accuse me of hypocrisy because I didn't mention the recent FDA warning letter to Genentech. My response is that I'm happy that the FDA sent that letter, assuming its charges are accurate. Unlike Burzynski's followers, I believe in one standard for everyone, including pharmaceutical companies and Burzynski's faux "research institute" when it comes to testing and marketing new therapies. I'd also say that what Burzynski did is clearly much worse in that Burzynski advertised an investigational drug as being safe and effective, while Genentech might have exaggerated the benefits of Tarceva and downplayed its risks. I would, however, tend to agree with Shaffer that the FDA should bring a bit more clarity as to what constitutes claims in promotional material and what does not, but I can make that assertion without equating Burzynski and Genentech, which is what BS would have me do. Even though it's pretty obvious that Burzynski went way beyond the line as he so frequently does and deserved a serious rebuke (which he frequently needs), more clarity can't help but be a good thing. Of course, more clarity regarding what does and does not constitute a promotional claim isn't what's desperately needed in the case of Burzynski. What's desperately needed in Burzynski's case is for the FDA (and the Texas Medical Board) to finally shut him down once and for all for his unethical and harmful activities. I only hope I live to see it.