Odds and ends left over after the Panorama Burzynski Clinic report: Burzynski versus his own SEC filing

I realize that I’ve been focusing on Stanislaw Burzynski the last couple of days, but it’s just been one of those weeks. Between the release of Eric Merola’s latest paean to the Brave Maverick Doctor and BBC Panorama’s report on Burzynski and his activities, it’s been an eventful week. My review of the second Burzynski movie and the Panorama report explain a lot, but there are some loose ends left over. So I might as well take care of that today before resuming regular blogging topics. (Yes, I know Stanislaw Burzynski is a regular blogging topic, but too much of a bad thing can get tiresome, no matter how much outrage I feel and express over his activities, leading to heapin’ helpings of not-so-Respectful Insolence.

As devastating as the Panorama story was, complete with Burzynski smirking his usual annoying, smug smirk and asking the reporter if he has Alzheimer’s disease because he’s asking him the same question (stay classy, Stash, stay classy), there were a lot of aspects dealt with little or not at all. First and foremost of those issues not dealt with whose absence was a huge mistake was the issue of the most recent FDA investigation of the Burzynski Clinic. It’s so bad that Josephine Jones is openly wondering whether Burzynski lied to the BBC. Regular followers of the Burzynski saga will remember that in January the FDA showed up at Burzynski’s operations to investigate. As Merola likes to harp on, FDA investigators stayed until March. Currently, we are awaiting the FDA’s decision, which is usually posted to the FDA website in the form of a formal letter. In any case, the reason this is relevant is because the FDA put a clinical hold on antineoplastons and barred the enrollment of any new patients on any of Burzynski’s protocols. Moreover, in response to a warning letter from the FDA last fall about promoting an unapproved drug, in January the Burzynski Clinic removed all references to antineoplaston therapy on its website, which is rather like Major League Baseball removing all references to, well, baseball on its website.

To recap, we know that last year a child suffered a severe adverse reaction to antineoplaston therapy, which led to the FDA putting a clinical hold on antineoplastons for children. Then, in January apparently, the clinical hold was placed on antineoplastons for adults as well, although apparently patients already receiving them could continue to do so. Actually, I wondered about that when I saw a rather fascinating part of the Panorama report, namely a tour of Burzynski’s manufacturing facility, which, we are told, can crank out 300 L of antineoplaston solution per day.

Which brings us to one of the odds and ends I wanted to touch upon, and it’s an issue that Josephine Jones touches on as well. Throughout Eric Merola’s infomercial for Burzynski and the BBC Panorama report, we are told by Burzynski, his acolytes, and his shills that antineoplastons will be approved by the FDA “soon,” that he’s been doing the trials to gain FDA approval over the last 15 or 20 years, and, oh, by the way, not to worry. We have been promised repeatedly that all those phase II clinical trials that Burzynski registered will similarly be published “soon.” Even Pete Cohen, Hannah Bradley’s partner, showed up on BBC Radio 5 promising that Burzynski is furiously submitting manuscripts for publication. But what’s really happening?

Josephine Jones points us to this recent SEC report for the Burzynski Research Institute for the fiscal year ending February 28, suggesting that we read the section entitled Partial Clinical Hold on Phase II and Phase III Clinical Trials. So I did. Now I’m not a businessman, and I don’t understand anything but the very basics of business. A lot of these SEC reports might as well be Greek to me, but I do know cancer science. I also know what Burzynski and his acolytes have been saying, one of which is that the phase III trial wil probably never be done because it’s “too expensive.” Yet in the report, we read:

On February 23, 2010, the Company entered into an agreement with Cycle Solutions, Inc., dba ResearchPoint (“Research Point”) to initiate and manage a pivotal Phase III clinical trial of combination Antineoplastons A10 and AS2-1 plus radiation therapy (RT) in patients with newly-diagnosed, diffuse, intrinsic brainstem glioma. Research Point has secured interest and commitments from a number of sites selected. Upon completion of this assessment, a randomized, international Phase III study will commence. The study’s objective is to compare overall survival of children with newly-diagnosed, diffuse, intrinsic brainstem glioma (DBSG) who receive combination Antineoplastons A10 and AS2-1 plus RT versus RT alone.

Three years should be plenty of time to line up clinical sites for a phase III trial. Of course, given that after three years the clinical trial hasn’t been opened, more than likely no reputable institution wants to partner with the Burzynski Research Institute, and ResearchPoint collected its checks. Then came the partial clinical hold, which affected this phase III trial as well as all the phase II trials, and, fortunately for patients, Burzynski’s antineoplaston operation is shut down. Revealed in the SEC report, of all places is why.

It’s a long excerpt, but I think it’s important. There’s a lot of legalese and FDA bureau-speak, but the meaning should be fairly clear to a layperson:

In a letter dated June 25, 2012, the Company informed the FDA of a serious adverse event which may have been related to the administration of Antineoplastons. On July 30, 2012, the FDA placed a partial clinical hold for enrollment of new pediatric patients under single patient protocols or in any of the active Phase II or Phase III studies under IND 43,742. The FDA imposed this partial clinical hold because, according to the FDA, insufficient information had been submitted by the Company to allow the FDA to determine whether the potential patient benefit justifies the potential risks of treatment use, and that the potential risks are not unreasonable in the context of the disease or condition to be treated. The FDA cited 21 C.F.R. § 312.42(b)(2)(i), 21 C.F.R. § 312.42(b)(1(iv), and 21 C.F.R. § 312.42(b)(3)(i), as grounds for imposition of a clinical hold; and 21 C.F.R. § 312.305(a)(2), a criteria for expanded access use. The FDA advised the Company that until it resolved the matter to FDA’s satisfaction, the Company could not enroll new pediatric patients in any protocol under such IND. The Company later notified the FDA in a September 24, 2012 letter that it was closing pediatric protocol BT-10 (under IND 43,742) for enrollment effective September 25, 2012, and that it would also terminate the protocol once all active patients had completed the study.

In other words, no more antineoplastons for children, not now, and, hopefully, not ever. Burzynski can continue to treat children on his protocols who had already started treatment, but that’s it. This is very good news. After all, the Burzynski Research Institute is shutting down the pediatric protocol.

This ultimately led to the partial clinical hold being extended to adults:

In a teleconference on January 9, 2013 between the FDA and the Company, followed by a letter of the same date, the FDA notified the Company that the agency was placing IND 43,742 on partial clinical hold, due to a lack of a complete response to the issues raised by the FDA and what the FDA deemed a misleading, erroneous, and incomplete investigator brochure. The FDA cited 21 C.F.R. § 312.42(b)(2)(i) and 21 C.F.R. § 312.42(b)(1)(iii), as grounds for imposition of a clinical hold. The FDA further advised the Company that until it resolved the matter to the FDA’s satisfaction, that the Company could not enroll new adult or pediatric patients in any protocol under such IND. The FDA also placed protocols B-52 and B-54 on clinical hold due to what the FDA deemed to be an unreasonable and significant risk of illness or injury to human subjects. The FDA cited 21 C.F.R. § 312.42(b)(2)(i) and 21 C.F.R.§ 312.42(B)(1)(i), as grounds for imposition of a clinical hold. The FDA advised the Company that until it resolved the matter to FDA’s satisfaction, the Company could not legally conduct the identified clinical studies under such IND.

In a letter dated April 9, 2013, the Company responded to the issues raised by the FDA in its January 9, 2013 letter to the Company. In a letter dated May 9, 2013 from the FDA, the FDA advised the Company that the Company’s April 9, 2013 letter was not a complete response to all the issues listed in the FDA’s letter dated January 9, 2013, and the FDA also identified the issues that were not fully addressed by the Company’s response. The FDA further advised the Company that until it satisfactorily addressed all the issues in the FDA’s letter dated January 9, 2013, that the FDA could not complete its review, and the clinical hold could not be removed.

So basically, the FDA extended its clinical hold; the Burzynski Research Institute answered the FDA’s charges; and the FDA was not satisfied. Until the Burzynski Research Institute can adequately address those concerns, there will be no new patients enrolled. If I were a betting man, I’d bet that no new patients ever will be enrolled because maybe, just maybe, the FDA is finally cracking down on Burzynski for real. At least, that’s whI hope. I’m all too aware that it looked just as bad for Burzynski in the 1990s, which was the last time the FDA made a serious run at the Burzynski Research Institute, and Burzynski managed to slither away, to come back bigger and stronger than ever. Even so, Burzynski’s own SEC filings suggest that all the bold talk of imminent approval of antineoplastons by the FDA and publication of the papers that will prove to the world that antineoplastons work are pipe dreams, stories to keep the marks on board and hoping. Indeed, even the report seems to concede that antineoplastons will likely never be approved, even going so far to point out that “the Company cannot predict if and/or when it will submit an NDA [New Drug Application] to the FDA, nor can the Company estimate the number or type of additional trials the FDA may require.” Burzynski also warns that “there can be no assurance that an NDA for Antineoplastons, as a treatment for cancer, will ever be approved by the FDA.”

That hardly sounds as though antineoplastons will be approved “soon.” After all, an NDA hasn’t even been submitted, and Burzynski is saying in his own SEC filings that he can’t predict when an NDA will be filed. Presumably if Burzynski were truly on the verge of getting antineoplastons approved by the FDA he would have said so in his SEC filing. That’s why his SEC filings are so revealing. Burzynski can distort, exaggerate, and even lie to the public, but lying on an SEC filing would carry serious consequences.

Notwithstanding the response results of the trials that have reached a Milestone, management believes it is likely that the FDA may require additional clinical trials based upon such protocols to be conducted by an institution not affiliated with the Company or Dr. Burzynski before advising that an NDA filing is warranted. In addition, the FDA has indicated it will not accept the efficacy data, but will accept toxicity data generated by the Phase II study according to Protocol CAN-1 because the trial was partially retrospective. At this time, the Company cannot predict if and/or when it will submit an NDA to the FDA, nor can the Company estimate the number or type of additional trials the FDA may require. Further, there can be no assurance that an NDA for Antineoplastons, as a treatment for cancer, will ever be approved by the FDA.

No assurance can be given that any new IND for clinical tests on humans will be approved by the FDA for human clinical trials on cancer or other diseases, that the results of such human clinical trials will prove that Antineoplastons are safe or effective in the treatment of cancer or other diseases, or that the FDA would approve the sale of Antineoplastons in the United States.

Another interesting tidbit in the SEC filing is Burzynski’s report of the results of several of his clinical trials. They aren’t really “results’ per se, in that the information presented really isn’t provided in a form that really allows other investigators to evaluate it and potentially replicate it. Basically it’s a big table listing Burzynski Research Institute clinical trials and response rates reported. One thing that I noticed right away is that in most trials, the number of evaluable patients is smaller, sometimes much smaller, than the number of patients accrued. This is a huge red flag. For instance, in trial BT-20, there were 40 patients accrued by only 22 were evaluable. This sort of dropoout rate is a huge red flag. We don’t know the reasons for this dropout rate. It could certainly skew the results, but even that’s impossible to tell from just a table of response rates and no further information. Of course, I realize that this is an SEC filing, not a scientific paper in the peer-reviewed literature, but if Burzynski has all this data to produce this table it boggles the mind that, given at least a decade and a half since these trials began, he hasn’t been able to publish any meaningful data thus far. That he hasn’t been able to do so is also a big red flag.

One can’t help but wonder why BBC Panorama didn’t look at this information. It could easily have fit into the narrative. Imagine a more prepared reporter, faced with the confident and sarcastic bloviation from Burzynski that antineoplastons will be approved “soon,” pulling out Burzynski’s own SEC filings and telling him that that’s not what he said in those filings. I can only imagine two reasons Bilton didn’t do that: The report wasn’t out when the interview occurred (which is possible, given the mentions of a date in early May) or lack of preparation. If it were the former situation, a more prepared reporter could have hammered Burzynski on how he could possibly say so confidently that antineoplastons were going to be approved “soon” with partial clinical holds by the FDA on children since the fall of 2012 and on adults since January 2013. These are hardly the sorts of issues that suggest imminent approval, contrary to Burzynski’s statements, which now must be viewed, in my opinion, as outright lies. Indeed, even if the SEC filing wasn’t published yet at the time this interview took place, imagine a voiceover tacked on after Burzynski’s statement pointing out that his own SEC filings contradicted his assertions. Moreover, bringing up these issues would arguably have fit into the narrative perfectly to point out that Burzynski is still promoting antineoplastons through surrogates by saying that FDA approval is imminent when, according to his SEC filing, he apparently hasn’t even filed an NDA yet. As much as the BBC got right in its coverage of Burzynski, aspects of its Panorama episode on Burzynski were pure frustration to those of us who have been following Burzynski for a while.