In the past year, much has changed for Jonnie R. Williams Sr. and his dietary supplement company, Star Scientific, Inc. In December 2013, the US Food and Drug Administration (FDA) sent a warning letter to Williams notifying him that two of his company’s products — Anatabloc® and CigRx® — did not meet the legal definition of a dietary supplement and were therefore adulterated under the Federal Food, Drug, and Cosmetic Act.1 Both products contain anatabine, a minor alkaloid present in small quantities in tobacco (Nicotiana tabacum, Solanaceae) and certain other plants (see Table 1), which the company promotes for its anti-inflammatory properties and smoking cessation benefits.2 Shortly thereafter, Williams stepped down as the CEO of Star Scientific, and by mid-2014 the company had rebranded itself as Rock Creek Pharmaceuticals, Inc. and moved its headquarters from Glen Allen, Virginia to Sarasota, Florida.3
In January 2014, less than a month after Williams resigned as CEO of the company he founded, Robert McDonnell, the former Republican governor of Virginia, and his wife, Maureen, were indicted on 14 criminal counts of corruption, filed in the US District Court for the Eastern District of Virginia.4 The McDonnells were charged with accepting more than $177,000 in loans and gifts from Williams in exchange for “official acts” performed by the governor and his office to promote Star Scientific products such as Anatabloc.5 Williams — the prosecution’s key witness — agreed to testify in exchange for full immunity.3
The McDonnells’ corruption trial began in late July 2014 and was the focus of much media attention.5 On August 11, two weeks after the trial began, Rock Creek Pharmaceuticals announced in its quarterly report to the Securities and Exchange Commission (SEC) that it was voluntarily halting sales of Anatabloc and CigRx, citing changing priorities for the company.6
“This action was taken in connection with an ongoing review of the extent to which our dietary supplement business … will impact our primary focus of developing pharmaceutical products from our anatabine-based compounds,” Rock Creek stated in the report.6 “[W]e anticipate that this will bring the FDA warning letter matter to a close.”
The legal matters of Bob and Maureen McDonnell are ongoing. On September 4, 2014, the former governor was found guilty of 11 corruption-related charges — including conspiracy, bribery, and extortion — and his wife was convicted on nine counts. A judge has scheduled sentencing for January 6, 2015, and the McDonnells’ legal team has vowed to appeal the jury’s decision.7
Tobacco for Health: A Brief History of Star Scientific
Williams, an entrepreneur and businessman, dabbled in a number of different ventures in the 1980s including car sales and optometry startups. In 1990, Williams founded Star Tobacco with the goal of making “safer” tobacco.8
“I don’t like tobacco,” Williams said in a Richmond Times-Dispatch article from 1988. “I am more interested in health care.”9
Star Scientific introduced smokeless tobacco products in the 1990s, and Williams eventually patented a tobacco-curing process using microwave radiation, which greatly reduced the amount of tobacco-specific nitrosamines, a group of potent carcinogens, in the dried plant material. In the late ’90s, the company significantly reduced the scope of its cigarette manufacturing operations, and Williams was appointed CEO of the newly renamed Star Scientific in 1999.9,10
“For most of its history as a maker of cigarettes, then smokeless tobacco, Star Scientific has presented itself as an innovator, seeking to bring change to an industry that for decades resisted it,” commented the author of a recent article in Richmond Times-Dispatch.10
In a span of roughly two decades, Star Scientific transformed from a cigarette manufacturer to a “technology-oriented company” concentrating on the nicotine-like chemical anatabine. The company’s new health-focused goal, according to Star Scientific, is “to develop a range of non-nicotine dietary supplements and related pharmaceutical products that could be beneficial in maintaining a healthy metabolism and in supporting good nutrition.”11
On August 5, 2010, Star Scientific launched CigRx, a dissolvable smoking cessation lozenge that contains anatabine and yerba maté (Ilex paraguariensis, Aquifoliaceae) as its active ingredients.14 One year later, the company introduced the dietary supplement Anatabloc, which retailed for $99.99 for a 30-day supply.2 According to its online description, “Anatabloc® leverages the body’s natural process for regulating its own inflammation using anatabine, a naturally-occurring compound found in some plants, combined with Vitamin A and D3.”2 In 2012, a $300 facial cream was added to the product line, promoted as being “infused with anatabine citrate, a rare ingredient that is exclusive to Anatabloc.”15
Star Scientific announced in December 2012 that it would focus on dietary supplements, officially severing ties with the tobacco industry. Despite Star Scientific’s revamped mission and new products, the company has reported 11 consecutive years of financial losses through 2013, according the most recent SEC report available.6
“Our future prospects,” Star Scientific notes in the report, “therefore are dependent on the expanded distribution and consumer acceptance of our dietary supplement products and cosmetic product.”6
McDonnells Indicted and Convicted of Corruption
Williams allegedly first became acquainted with Bob McDonnell during his 2009 gubernatorial race, when McDonnell’s staff requested the use of Williams’ private jet for campaigning purposes. Shortly after McDonnell was elected governor of Virginia, Williams asked to meet with the McDonnells at a political event in New York City, and they remained in varying degrees of contact through March 2013.4
The federal indictment charges that over a period of roughly two years, the McDonnells schemed to provide “official actions … to legitimize, promote, and obtain research studies for Star Scientific’s products, including Anatabloc®” in exchange for loans and gifts from Williams, reportedly totaling more than $177,000.4,5
McDonnell — whose campaign slogan was “Bob’s for Jobs” — has maintained that any actions he took to support Williams or Star Scientific were consistent with his goal to promote Virginia businesses.16
The 43-page indictment provides numerous examples of such “official actions” performed by McDonnell, including the following:
“Arranging meetings for [Williams] with Virginia government officials, who were subordinates of the Governor, to discuss and promote Anatabloc®;
“Hosting, and the defendants attending, events at the Governor’s Mansion designed to encourage Virginia university researchers to initiate studies of anatabine and to promote Star Scientific’s products to [medical] doctors for referral to their patients;
“Contacting other government officials in the OGV [Office of the Governor of Virginia] as part of an effort to encourage Virginia state research universities to initiate studies of anatabine;
“Promoting Star Scientific’s products and facilitating its relationships with Virginia government officials by allowing [Williams] to invite individuals important to Star Scientific’s business to exclusive events at the Governor’s Mansion; and
“Recommending that senior government officials in the OGV meet with Star Scientific executives to discuss ways that the company’s products could lower healthcare costs.”4
Maureen McDonnell, who, according to her daughter’s court testimony, had a “mild obsession” with Williams, also was allegedly involved in promoting Anatabloc in return for luxury gifts, including designer clothes, shoes, and a $6,500 Rolex for her husband.4 At a campaign event for Mitt Romney in 2012, Maureen — who was “particularly enthusiastic” about Anatabloc — reportedly suggested to Ann Romney that the supplement “could potentially cure [her] multiple sclerosis.”18
Legal and Regulatory Concerns
On December 20, 2013, anatabine became the latest dietary supplement ingredient with claimed botanical origins to receive a warning letter from the FDA. However, in contrast with recent FDA actions against supplements with controversial “botanical” ingredients — e.g., DMAA (1,3-dimethylamylamine) and dendrobium (Dendrobium nobile, Orchidaceae) extract — the FDA did not comment on the natural or synthetic source of anatabine in Star Scientific’s products. Instead, the agency focused on the product’s therapeutic claims and anatabine’s new dietary ingredient (NDI) and investigational new drug (IND) status.1
According to the FDA’s warning letter, Star Scientific’s website “promotes the product Anatabloc for conditions that cause the product to be a drug under section 201(g)(1)(B) of the Federal Food, Drug, and Cosmetic Act.”1
In the “Health Research” section of its website — which has since been taken down — Star Scientific cited studies that suggested anatabine may be helpful in treating multiple sclerosis, mitigating “neuro-inflammatory conditions,” preventing ulcerative colitis, treating Alzheimer’s disease, and “alleviat[ing] the negative consequences of traumatic brain injury.”1
At the time of this writing (October 2014), only two randomized, controlled human clinical trials have been published on anatabine. The first study, published in July 2013, found no benefit of anatabine over placebo in muscle damage indicators or strength recovery in 18 men following strenuous workouts.19 The second study, published a few months later, examined the effects of anatabine in 146 participants with Hashimoto’s disease,20 a condition otherwise known as chronic lymphocytic thyroiditis.21 The authors found that anatabine had an impact on the levels of one thyroid antibody and recommended further study. (Both studies were funded by Rock Creek Pharmaceuticals and included company employees as authors.)
Star Scientific noted in its most recent annual SEC filing that it was taking steps to address some of the concerns in the warning letter. “In light of our receipt of the FDA letter, we have substantially limited the marketing and advertising of our dietary supplements,” the company wrote.11
INDs & NDIs
According to the FDA’s warning letter, anatabine was authorized as an IND on June 8, 2012.1 On August 11, 2014, however, the FDA notified Rock Creek Pharmaceuticals that its IND application had been put on a clinical hold pending clarification of previously submitted data.6
As the FDA explains online, an IND application is designed “to determine if the product is reasonably safe for initial use in humans.”22 Importantly, the FDA continues, an “IND is not an application for marketing approval. Rather, it is a request for an exemption from the Federal [statute] that prohibits an unapproved drug from being shipped in interstate commerce.”22
“Under section 201(ff)(3)(B)(ii) of the [Food, Drug and Cosmetic] Act,” the FDA notes, “a dietary supplement may not include an article authorized for investigation as a new drug for which substantial clinical investigations have been instituted and made public, unless the article was marketed as a dietary supplement or food before its investigation was authorized.”1
Anatabine’s IND authorization, as detailed in the December 20 warning letter, thus complicates Anatabloc’s classification as a dietary supplement. Star Scientific began marketing Anatabloc one year before and CigRx two years before anatabine’s June 2012 authorization as an IND. According to FDA’s warning letter, however, because anatabine is considered an NDI, and Star Scientific had failed to comply with legal requirements to provide the FDA notice within 75 days prior to introducing Anatabloc into the US market as an NDI, the marketing of anatabine prior to the IND authorization was not lawful.
Therefore, anatabine was not “marketed” as a dietary supplement before it obtained status as a “drug” under the relevant provision of federal law (i.e., 21 USC§ 321(ff)(3)(B)(ii)). And, according to the FDA, the company’s failure to file an NDI notification (NDIN) for the compound — before it sought to study anatabine as a new drug — disqualifies it from the definition of dietary supplement and precludes its marketing as a dietary supplement.1
In June 2014, Star Scientific submitted an NDI notification for anatabine in an attempt to address this issue, qualifying its decision in the August SEC report: “Although the company does not believe that an NDIN is a prerequisite to the lawful marketing of the nutritional supplement,” the company explains, “the NDIN was voluntarily submitted to provide the FDA with preclinical and clinical data concerning the supplement.”6 On September 12, 2014, the newly renamed Rock Creek Pharmaceuticals — formerly the name of a Star Scientific subsidiary, and, as of June 2, the company’s official new name — announced that it had received a response from the FDA regarding their NDIN. The FDA, reiterating certain points from the 2013 warning letter, responded in opposition to the request, telling the company that they consider anatabine citrate to be a drug that is “the subject of a previously filed Investigational New Drug Application.”23
Presence in Food & Origin of Anatabine
Unlike the previously mentioned example of DMAA — which has yet to be definitively proven to exist naturally in botanicals24 — anatabine is known to be present in small quantities in certain plants such as tobacco, tomatoes, potatoes, and eggplant (see Table 1).1,12,13 However, this does not automatically qualify anatabine as a so-called old dietary ingredient (i.e., the term frequently used to refer to an ingredient marketed prior to October 15, 1994, when Congress passed the Dietary Supplement Health and Education Act of 1994).
“[T]he mere presence of anatabine in such foods, without any evidence the foods were promoted for their anatabine content,” the FDA states in the warning letter, “does not constitute ‘marketing’ of anatabine as a food under section 201(ff)(3)(B).”1
Although the FDA did not go into detail about the natural or synthetic derivation of anatabine in Star Scientific’s supplements, several publicly available documents suggest a possible synthetic origin. In an archived version of Anatabloc’s website under the question heading “Does Anatabloc® contain Tobacco?” the company states: “Although we first looked at the anatabine alkaloid in tobacco plants, the anatabine in Anatabloc is not derived from tobacco.”25
On March 23, 2010, Rock Creek Pharmaceuticals filed a patent titled “Methods of synthesizing anatabine.” According to the document, “The present invention relates to improved methods of synthesizing anatabine, especially methods that are useful in larger scale syntheses.”22
McDonnell, who has claimed that his support of Anatabloc was part of his job as governor to promote Virginia businesses, originally was not aware of the compound’s synthetic origin. “It was only later that McDonnell learned, he said [in his court testimony on August 22, 2014], that Star synthesized anatabine out of state instead of drawing it from tobacco leaves.”26
Perhaps the most straightforward reason why the FDA claims Anatabloc is not a legal dietary supplement is because anatabine is found in — and can be derived from — the tobacco plant. “[I]t appears that anatabine can be manufactured from tobacco,” the FDA observes in its warning letter.1 “It is important to note that tobacco, including its constituents, is excluded from the definition of ‘dietary supplement’ under section 201(ff)(1) of the Act” (see Table 2).
After the McDonnells’ roughly six-week federal trial — “the biggest trial in Virginia political history”27 — it took the jurors less than two days to render a verdict. Pending an appeal, Bob McDonnell could face up to 10 years in prison for his corrupt dealings with Williams.28
In his 23 years as the head of Star Scientific, Williams oversaw the company’s transition from a cigarette manufacturer to an innovative dietary supplement business. However, in just the past year, new legal, regulatory, and financial issues have put the company in a state of flux once again.
The tone of Rock Creek Pharmaceutical’s most recent SEC quarterly report is, at times, decidedly somber. “Since the introduction of Anatabloc®, the Company’s revenues have been derived almost exclusively from the sale of this product. Future sales of the Company’s dietary supplements will be dependent on it resolving issues with the [FDA] relating to the status of its Anatabloc® and CigRx® products,” the report states.10 “In the long term, the Company expects that its revenues will shift to be more dependent on the ability to successfully implement its drug development program, but it has no drug products in advance development as of this date.”
Bob McDonnell’s future remains uncertain as well. Less than two weeks after his conviction, McDonnell asked a federal judge to be acquitted of his charges, claiming that there was “insufficient evidence” and that the term “official acts” was improperly defined during his trial.29 McDonnell’s lawyers will appeal the verdict after his sentencing on January 6, 2015. It remains to be seen what impact this ongoing case will have on the future of Rock Creek Pharmaceuticals and Anatabloc.
- Star Scientific, Inc. 12/30/13 warning letter. US Food and Drug Administration website. Available at: www.fda.gov/iceci/enforcementactions/warningletters/2013/ucm379639.htm. Accessed August 29, 2014.
- Anatabloc: 300ct original bottle. Anatabloc website. Available at: https://store.anatabloc.com/anatabloc-original-300. Accessed September 2, 2014.
- Green F. Former Star Scientific CEO Williams lands immunity. Richmond Times-Dispatch. July 12, 2014. Available at: www.roanoke.com/news/virginia/former-star-scientific-ceo-williams-lands-immunity/article_5a2f6878-fe6c-5b84-9dbc-077c444bf104.html. Accessed September 2, 2014.
- United States of America v. Robert F. McDonnell (Counts 1-13) and Maureen G. McDonnell (Counts 1-11, 13-14), defendants. Indictment. January 21, 2014. Available at: www.documentcloud.org/documents/1008135-mcdonnell-indictment.html. Accessed August 26, 2014.
- Zapotosky M, Weiner R. Judge sets July trial for former Va. governor McDonnell. Washington Post. January 24, 2014. Available at: www.washingtonpost.com/local/crime/former-va-gov-robert-f-mcdonnell-to-appear-in-court/2014/01/24/f7041bf4-8480-11e3-8099-9181471f7aaf_story.html. Accessed September 2, 2014.
- Rock Creek Pharmaceuticals, Inc. Quarterly report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the quarterly period ended June 30, 2014. Securities and Exchange Commission website. Available at: http://app.quotemedia.com/data/downloadFiling?webmasterId=101533&ref=9747442&type=HTML&symbol=RCPI&companyName=Rock+Creek+Pharmaceuticals+Inc&formType=10-Q&dateFiled=2014-08-11&cik=0000776008. Accessed September 3, 2014.
- Gabriel T. Virginians, surprised by ex-governor’s conviction, ponder the fallout. New York Times. September 6, 2014. Available at: www.nytimes.com/2014/09/06/us/juror-says-evidence-against-ex-virginia-governor-was-overwhelming.html?_r=0. Accessed September 6, 2014.
- Helderman RS, Vozzella L. Jonnie R. Williams, key witness against McDonnells, has a complicated past. Washington Post. February 3, 2014. Available at: www.washingtonpost.com/local/virginia-politics/jonnie-r-williams-key-witness-against-mcdonnells-has-a-complicated-past/2014/02/03/8886cc36-8768-11e3-833c-33098f9e5267_story.html. Accessed September 2, 2014.
- Moomaw G. Star Scientific CEO has a long history of salesmanship. Richmond Times-Dispatch. April 7, 2013. Available at: www.timesdispatch.com/business/tobacco-industry/star-scientific-ceo-has-a-long-history-of-salesmanship/article_0619cc78-b591-550b-b2f3-2f816e723f77.html. Accessed September 2, 2014.
- Blackwell JR. Star Scientific’s next controversy? Dietary aids. Richmond Times-Dispatch. April 14, 2013. Available at: www.timesdispatch.com/business/economy/star-scientific-s-next-controversy-dietary-aids/article_a53f0f10-a332-5bfb-a0cb-89c9d7400c5f.html. Accessed September 2, 2014.
- Rock Creek Pharmaceuticals, Inc. Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 for the quarterly period ended December 31, 2012. Securities and Exchange Commission website. Available at: www.sec.gov/Archives/edgar/data/776008/000114420413015866/v336730_10k.htm. Accessed September 3, 2014.
- Rock Creek Pharmaceuticals, Inc. EP 2751091 A2: Products for anti-inflammation support. Filed July 12, 2012. Available at: www.google.com/patents/EP2751091A2?cl=en. Accessed August 26, 2014.
- Anatabine. Dr. Duke’s Phytochemical and Ethnobotanical Databases. August 18, 2014. Available at: www.ars-grin.gov/cgi-bin/duke/chemical.pl?LANATABINE. Accessed September 2, 2014.
- How it works. CigRx website. Available at: https://cigrx.com/. Accessed September 2, 2014.
- Anatabloc rare cellular facial crème. Anatabloc website. Available at: https://store.anatabloc.com/anatabloc-rare-cellular-facial-cr%C3%A8me. Accessed September 2, 2014.
- Glueck K. Bob McDonnell testifies on marriage woes. Politico. August 20, 2014. Available at: www.politico.com/story/2014/08/bob-mcdonnell-trial-110195.html. Accessed September 2, 2014.
- Vasiliadis J. Defense rests in trial of former Virginia governor. USA Today. August 27, 2014. Available at: www.usatoday.com/story/news/politics/2014/08/27/bob-mcdonnell-corruption-trial/14682191/. Accessed September 2, 2014.
- The five weirdest revelations from the McDonell trial. Daily Beast. August 21, 2014. Available at: www.thedailybeast.com/articles/2014/08/21/the-five-weirdest-revelations-from-the-mcdonnell-trial.html. Accessed September 2, 2014.
- Jenkins NDM, Housh TJ, Johnson GO, et al. The effects of anatabine on non-invasive indicators of muscle damage: a randomized, double-blind, placebo-controlled, crossover study [published online July 22, 2013]. Journal of the International Society of Sports Nutrition. 2013;10:33. Available at: www.jissn.com/content/10/1/33. Accessed September 8, 2014.
- Schmeltz LR, Blevins TC, Aronoff SL, et al. Anatabine supplementation decreases thyroglobulin antibodies in patients with chronic lymphocytic autoimmune (Hashimoto’s) thyroiditis: a randomized controlled trial. Journal of Clinical Endocrinology and Metabolism. 2014;99(1). Available at: www.ncbi.nlm.nih.gov/pmc/articles/PMC3928963/. Accessed September 2, 2014.
- Hashimoto’s disease. Mayo Clinic website. Available at: www.mayoclinic.org/diseases-conditions/hashimotos-disease/basics/definition/con-20030293. Accessed September 2, 2014.
- Drug development and review definitions. US Food and Drug Administration website. Available at: www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationalnewdrugindapplication/ucm176522.htm. Accessed September 2, 2014.
- Rock Creek Pharmaceuticals receives new dietary ingredient notification (NDIN) response [press release]. Sarasota, Florida: Rock Creek Pharmaceuticals; September 12, 2014. Available at: www.nasdaq.com/press-release/rock-creek-pharmaceuticals-receives-new-dietary-ingredient-notification-ndin-response-20140912-00242. Accessed October 9, 2014.
- Smith T. New research supports synthetic origin of DMAA in supplements. HerbalGram. 95;46-49. Available at: http://cms.herbalgram.org/herbalgram/issue95/hg95-feat-dmaa.html. Accessed September 3, 2014.
- Frequently asked questions about Anatabloc®. Anatabloc website. Available at: https://web.archive.org/web/20130825202217/http:/anatabloc.com/faq/. Accessed September 2, 2014.
- Rock Creek Pharmaceuticals, Inc. US Patent 8,207346 B2: Methods of synthesizing anatabine. Filed March 23, 2010. Available at: http://pdf.sumobrain.com/US8207346B2.pdf?AWSAccessKeyId=AKIAIBOKHYOLP4MBMRGQ&Expires=1409789620&Signature=HTl2XSaNkp2jUDOCEjy4UX9QFnk%3D#view=FitH. Accessed August 26, 2014.
- Fain T. McDonnell trial: Former governor sees coincidence, not conspiracy in government’s case. Daily Press. August 22, 2014. Available at: www.dailypress.com/news/politics/dp-20140822,0,5363262.story. Accessed September 2, 2014.
- Vozzella L. Outcome of McDonnell corruption trial may hinge on couple’s alleged marital woes. Washington Post. September 1, 2014. Available at: www.washingtonpost.com/local/virginia-politics/outcome-of-mcdonnell-corruption-trial-may-hinge-on-couples-marital-woes/2014/09/01/03f180aa-2ea8-11e4-9b98-848790384093_story.html. Accessed September 2, 2014.
- Zapotosky M. Ex-Va. governor Robert McDonnell asks for acquittal of public corruption charges. Washington Post. Available at: www.washingtonpost.com/local/virginia-politics/ex-va-governor-robert-mcdonnell-asks-for-acquittal-of-public-corruption-charges/2014/09/18/db5f6f3c-3f99-11e4-9587-5dafd96295f0_story.html. Accessed October 9, 2014.