A federal corruption probe involving a prominent U.S. governor and his wife over potential gifts from a wealthy CEO of a dietary supplement company?
So what do I find most interesting?
What's in those supplements that facilitated the CEO's wealth?
Last week, former Virginia governor Robert F. McDonnell and his wife, Maureen, were indicted for allegedly accepting "loans and gifts of money, clothes, golf fees and equipment, trips, and private plane rides" valued at $165,000 from Jonnie R. Williams, Sr., former CEO of Star Scientific.
The 43-page indictment includes the charge that Williams' support would in turn garner favor from the governor's office for his Glen Allen, Virginia-based company under McDonnell's expressed priority "to promote the matter and cause of economic development for businesses and industries in Virginia." McDonnell's campaign slogan was, "Bob's for Jobs."
Star Scientific had been struggling as of late due in part to action by the U.S. Food and Drug Administration questioning the company's marketing of their two major products: Anatabloc, "anti-inflammatory support of the immune system," and CigRx, for smoking cessation. These concerns culminated with an exhaustively-documented FDA warning letter to Williams and Star Scientific dated December 20, 2013.
What is anatabine and what does it do?
The supplement product lines contain a naturally-occurring chemical called anatabine, a close relative of nicotine. Anatabine is a minor component of tobacco and has been used as a biomarker for tobacco use in human studies of nicotine patches for smoking cessation. Anatabine is also found in plants from the Solanaceae family, food plants such as tomatoes, peppers, cauliflower, eggplants and potatoes.
Anatabine is certainly an interesting chemical from a pharmaceutical standpoint. In vitro data with human blood and in vivo mouse studies indicate that it can inhibit the production of cytokines triggered by inflammatory stimulators by preventing activation of a transcriptional regulatory protein called STAT3. What's not known is whether anatabine would reach these active concentrations in people who take the supplements. But that's what a Phase I clinical trial is for, something that's not required for dietary supplements.
In October, results from a human trial of anatabine (oddly promised in a press release last January) were published online in the Journal of Clinical Endocrinology and Metabolism. Rock Creek-funded a nine-site, placebo-controlled clinical trial of three-times-daily anatabine in 165 patients with Hashimoto's thyroiditis.
The responses varied wildly across individual patients: "Mean ± SD TgAb values decreased by 46.2 ± 101.1 and 3.9 ± 83.9 World Health Organization units for the anatabine and placebo groups, respectively." But a significantly higher number of anatabine-treated subjects experienced a ≥20% decrease in anti-thyroid antibodies relative to the placebo group. However, 36% of patients reported dizziness even though researchers started with a low dose to prevent this nicotinic side effect.
Hashimoto's, or chronic lymphocytic autoimmune thyroiditis, was the first autoimmune disease described and is characterized by antibody-mediated attack of the thyroid gland. The rationale for the study was that tobacco smokers and airline flight attendants exposed occupationally to tobacco smoke back in the old days experience Hashimoto's thyroiditis at lower incidence than the total population. These observations led researchers to hypothesize that something in tobacco smoke might protect individuals from this thyroid disease.
The accounts of this work are tangled, and were misstated in earlier versions of this article. Some Star-sponsored work on anatabine in mice had been published by Johns Hopkins University’s Dr. Paul W. Ladenson, director of their division of endocrinology, metabolism and diabetes. He also commented in a Star press release about human studies of the drug he was not involved in. The Street’s Adam Feuerstein charged that Star Scientific had inappropriately promoted their human trial as being associated with Hopkins. Feuerstein wrote a scorching review of that episode last January. A lawsuit has been filed alleging wrongdoing by Star Scientific; the company denies any wrongdoing.
(Star Scientific's VP of Communications and Investor Relations Tahlia Tuck reminded me that Dr. Ladenson was involved in the ASAP trial, not as a site director but in the capacity of "senior endocrinological consultant for the study," as described in their January 7, 2013 press release.)
Ladenson's work was supported by private philanthropy so I took a look at NIH's grants database to see if the nation's medical research agency has funded any work on anatabine as a therapeutic agent. Thus far, only three investigators have received support for anatabine work, all from the National Institute on Drug Abuse and only as a biomarker in smoking cessation studies (Dr. Sharon M. Hall, UCSF, 2001-2008; Dr. Stephen S. Hecht, University of Minnesota, 2004-2008; and Dr. Cheryl Ann Oncken, University of Connecticut, 2002, 2006).
Sorry – it's a drug, not a supplement
From a regulatory standpoint, Star Scientific seems to have begun digging their grave since 2010 when they began citing scientific studies of anatabine, done mostly in rodents, to make drug claims for their products on their website. Moreover, they were marketing their products under dietary supplement claims that anatabine was a naturally-occurring food constituent.
However, the December 20th FDA warning letter states,
To the best of FDA’s knowledge, there is no information demonstrating that anatabine has been present in the food supply as an article used for food in a form in which the food has not been chemically altered. Although anatabine is present as an inherent constituent of foods such as cauliflower, eggplant, potatoes, and tomatoes, FDA is not aware of any information indicating that anatabine itself is an article used for food. In the absence of such information, anatabine is a new dietary ingredient subject to the premarket notification requirement in section 413(a)(2) of the Act [21 U.S.C. § 350b(a)(2)] and 21 CFR 190.6.
As such, the FDA has ruled that Anatabloc and CigRx are adulterated with an unapproved drug, particularly since an unidentified firm had filed an Investigational New Drug application (IND) with the FDA in June, 2012. The sponsor isn't Star Scientific or Rock Creek because they are still only talking about filing an IND as of their shareholder meeting at the end of last year. When I contacted FDA for information on the IND sponsor, media officer Juli Putnam reminded me,
The FDA cannot comment on any current/pending product applications. The FDA is only able to provide information on approved drug product applications. Any information on an application that has yet to receive an approval or was denied approval belongs to the manufacturer/sponsor developing the drug (21 CFR 314.430).
Star Scientific and their subsidiary, Rock Creek Pharmaceuticals, did themselves no favors when they promoted Rock Creek's U.S. patent for an "improved method of synthesizing anatabine that facilitates large scale commercial production of high purity anatabine (U.S. Patent No. 8,207,346). And just in October, they were awarded another U.S. patent for the citrate salt of anatabine, the form of the drug in their products.
The implication is that the company wasn't using a plant extract as might an herbal medicine company. Instead, they were making an unapproved, synthetic drug that was then being formulated into tablets for Anatabloc and CigRx, as well as two facial cosmetics under the Anatabloc brand. While the company claims they're conducting a two-track business plan – one for dietary supplements and one for a single-molecule pharmaceutical – the FDA clearly states in their warning letter that the supplements are being marketed as an unapproved drug.
On a New Year's Eve report, WAMU-FM's Rebecca Blatt quoted Dr. Daniel Fabricant of the FDA's Division for Dietary Supplement Programs,
“The question put for them is how exactly is the ingredient in Anatabloc a lawful dietary supplement?” Fabricant says. “How can it be sold at all?”
Putting the chemical structure of anatabine on their labels – inaccurately drawn, by the way – implies to the consumer that a real drug can be found within.
It's unclear how Star Scientific, now fully known as Rock Creek Pharmaceuticals, will respond to the FDA warning letter. But in the wake of this and the McDonnell scandal, Jonnie Williams has resigned as CEO but will stay on for a year in a non-executive capacity. He has been replaced by Dr. Michael Mullen, scientific director of Florida's Roskamp Institute, the sponsor of an anatabine trial in Alzheimer's disease patients.
If you're interested in more on the company, Richmond-based freelance writer Peter Galuszka has a deeply-reported backgrounder on Williams at The Hook.
*Correction: I had stated in the original version of this post that Star Scientific had inappropriately promoted their ASAP trial as having been done at Johns Hopkins, which Star Scientific denies. A January 7, 2013 press release, no longer available at their site but archived at PR Newswire, could give this impression. In a second version, based on reader complaints, I challenged Feuerstein's reporting. Upon further review of company press releases and Feuerstein's columns, I confirm that Feuerstein's reporting accurately stated that Star Scientific and analysts had touted the ASAP study as being associated with Hopkins and, on January 23, that Hopkins categorically denied any involvement. Feuerstein also correctly stated that the only true relationship between Star and Hopkins was with the previous preclinical study on anatabine in a mouse model of thryoiditis. I regret the errors.
