A gastroenterology journal has issued expressions of concern for forty articles about a probiotic formulation that has been at the center of a long-running legal saga in the United States and Europe.
The articles appeared in the Journal of Crohn’s and Colitis, the official journal of the European Crohn’s and Colitis Organisation (ECCO) and date back to 2007. All mention a proprietary formulation of probiotics – and therein lies the tale.
The formulation in question was developed decades ago by an Italian researcher named Claudio De Simone. Until 2016, the formulation was sold in United States by Sigma-Tau as VSL#3 – and was referred to as such in scores of journal articles in the gastroenterology literature. In Europe and Canada, Ferring Corp. had the rights to sell VSL#3, although it ceased doing so a few years ago (more on that in a moment).
But De Simone had a falling out with Sigma-Tau and its parent company and joined forces with another firm, ExeGI. And he brought VSL#3, to which he claimed rights, with him.
Sigma-Tau (which had merged with another firm to become Alfasigma) continued to sell a version of the formulation under the name VSL#3. De Simone and ExeGI objected, and sued the company for false advertising. Among the allegations was that Alfasigma was citing clinical studies of VSL#3 without noting that the product used in those trials was not identical to the one it was now selling.
In 2018, a federal court ruling in Maryland agreed, awarding De Simone nearly $20 million in damages and other fees in the case – a judgment that was upheld on appeal. The ruling also barred Alfasigma from citing trials of the De Simone formulation as if it were its own product.
At this point, an author’s note is warranted. As editor of Gastroenterology & Endoscopy News, one of us (AM) published a review article on probiotics that included several studies of VSL#3. That prompted a threatening letter from an attorney for ExeGI demanding that we:
and the Article’s authors disclose to it all communications and other information sufficient to determine the role of Alfasigma, or its licensor VSL Pharmaceuticals, Inc., or any person or entity acting in concert or participation with them, that may have influenced the preparation of the Article. Furthermore, ExeGi requests that the journal publish an update to recognize that the formulation studied under the name VSL#3 is now only available under the trademark Visbiome, and that there are no published human trials in Pouchitis, UC or HE using the current VSL#3 product. We appreciate that the authors and the journal’s editors want to ensure that doctors and patients receive accurate scientific information. We note the importance the journal’s editor places on scientific accuracy, as reflected in his publication of the www.retractionwatch.com blog, which does an excellent job highlighting the clinical retractions that do periodically take place.
In the aftermath of the 2018 U.S. ruling, a fair trade NGO in Europe brought its own legal challenges against both Ferring and ECCO. De Simone, a witness in the cases but not a party to them, says Ferring settled. However, De Simone accused ECCO of continuing to ignore a ruling that would require it to note the difference between the original formulation of the probiotic and other versions.
According to De Simone, the society has so far been sanctioned financially multiple times in the matter.
The Journal of Crohn’s and Colitis has now issued the following notice:
The probiotic which has been referred to as VSL#3 in Journal of Crohn’s and Colitis (JCC) publications is the subject of several ongoing legal disputes in different countries. Some of these disputes regard JCC publications. The plaintiffs claim that the formulation of VSL#3 that has been assessed in studies cited in JCC is different from the formulation of VSL#3 that is currently available on the market. As the legal disputes and scientific examinations on this question are still ongoing, Journal of Crohn’s and Colitis readers should be aware that the formulation of the currently available VSL#3 may not be the same as the VSL#3 that has been scientifically assessed in studies that are subject of this article or are referenced to in this article. The readers are invited to read the Letter to the Editor from the Governing Board of ECCO on this subject https://doi.org/10.1093/ecco-jcc/jjab225.
That letter states, in part:
Although the legal disputes and scientific examinations on this question are still ongoing, ECCO has been obliged by a temporary court injunction not to refer to this probiotic without a clarification note. Thus, ECCO would like to draw the readers’ attention to this issue. Readers should be aware that the formulation of the currently available VSL#3 may not be the same as the VSL#3 that has been scientifically assessed in studies that are subject of JCC articles or that are referenced in JCC articles.
ECCO has made every effort to compile a list of articles that are affected by this issue.1–40 However, this list should not be considered comprehensive and complete.
Starting even before this temporary injunction was issued, ECCO already moved in the more recent ECCO Topical Reviews [ECCO Topical Review: Complementary Medicine and Psychotherapy in IBD, and ECCO Topical Review: Refractory Inflammatory Bowel Disease] to a generic description of the strain mixture contained in this probiotic, as follows: ‘A multistrain probiotic containing eight different probiotics [Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, Streptococcus thermophilus].
The editor of the journal did not immediately respond to a request for comment.
De Simone says he is “not at all” satisfied with the expressions of concern and that he believes the journal’s description of the probiotic mix “fraudulent” and “even worse” than the status quo.
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The issue seems to be one of patent law more than anything else.
In an undated letter on the Visbiome website, de Simone states that
“In the early 1990s, I invented the 8-strain, high potency probiotic which was….. sold with the brand name VSL#3…”
and follows this up with
“For more than two decades, I have protected the secret formula required to produce this probiotic….”
It is astounding that over 40 so-called scientific trials in serious gastrointestinal diseases have been carried out using a treatment
“ (with a) secret formula….” Where were the institutional controls over such trials in humans and where were the editors who published the results of a “secret formula” ?
The comparison that immediately springs to mind is the snake oil salesman of the nineteenth century who would sell preparations “with a secret formula” to unsuspecting yokels.