Table 4. UK and US off-label promotion cases involving the same drug for the same off-label use.
| Drug | Company | Off-label Use | UK Case Summary | Year | Charge | US Case Summary 1 | Year | Settlement 2 |
|---|---|---|---|---|---|---|---|---|
| Aranesp (darbepoetin alfa) | Amgen | Unauthorized dosing regiment | Aranesp was approved for use once a week. However, advertisement quoted a paper entitled “Darbepoetin Alfa Administered Every 2 Weeks Alleviates Anemia in Cancer Patients Receiving Chemotherapy.” The implication of using Aranesp every 2 wk was that the initial dose would be higher. (no. 1554/2/04) | 2004 | £2,500 | From 2002 until 2007, Amgen allegedly promoted Aranesp for (1) unapproved dosing regiments and (2) unapproved indications. Regarding the former, the complaint accused Amgen of building the Aranesp commercial strategy around a less frequent dosing schedule but with doses that were two to four times larger than approved. | 2012 | US$762 million 3 |
| Seretide (UK), Advair (US) (fluticasone/salmeterol) | GlaxoSmithKline | Mild COPD | Seretide was licensed in a restricted group of COPD patients, i.e., those with severe disease and a history of repeated exacerbations, who had significant symptoms despite regular bronchodilation. Furthermore, only one of the six Seretide formulations was so licensed. Claim in detail aid and journal ad, “Seretide in COPD,” without qualification implied that all formulations of Seretide could be used in any patient with COPD and this was not so. (no. 1551/2/04) | 2004 | £2,500 | GSK allegedly promoted Advair off-label (1) for mild COPD and (2) as first-line therapy in mild asthma. Regarding the former, the complaint accused GSK of building the Advair commercial strategy around its “Only 1” campaign (July 2008–June 2010), which encouraged prescribing to patients who had had only one exacerbation. GSK allegedly made false and misleading statements about relevant treatment guidelines, trained representatives to lie about the guidelines, and gave representatives buttons to wear with the phrase “only one.” | 2012 | US$25 million 4 |
| Abilify (aripiprazol) | Otsuka (UK, US) Bristol-Myers Squibb (UK) | Nonschizophrenic psychotic disorders | Abilify was indicated for schizophrenia. Leave piece announcing launch stated “Highly effective symptom control in acute psychosis” and “Abilify helped to control the symptoms of acute psychosis as early as week 1.” However, schizophrenia is only one of the very many causes of acute psychosis, e.g., mania, depression, and drug abuse. (no. 1623/8/04 and 1624/8/04) | 2004 | £2,500 | Allegations that, from 2002 through the end of 2005, Otsuka promoted Abilify off-label for (1) paediatric use and (2) to treat dementia-related psychosis. Regarding the latter, the complaint accused Otsuka representatives of participating in a specialized long-term care sales force that called almost exclusively on nursing homes, where dementia-related psychosis is far more prevalent than schizophrenia or bipolar disorder for which the drug was licensed. | 2008 | US$4 million |
| Risperdal (risperidone) | Johnson & Johnson (Janssen) | Children | J&J subsidiary Jansen issued advertisement featuring a lone female figure in a playground walking away from a trail of articles that included a doll, photograph album, wedding veil, handbag, and toothbrush. The impression that the figure had possibly once owned the articles on the ground was compounded by the adjacent text “Prescribe early, because what she loses, she could lose forever.” The statement “Prescribe early” implied that the figure in the photograph was a young person. The Risperdal SPC stated that the product had not been studied in children or adolescents younger than 18 y. (no. 2059/10/07) | 2007 | £2,500 | From 1999 through 2005, Janssen allegedly promoted Risperdal for use in children, individuals with mental disabilities, and elderly dementia patients. J&J and Janssen allegedly knew that Risperdal posed certain risks to children, including risk of hormonal disturbances. Nonetheless, one of Janssen’s Key Base Business Goals was to grow and protect the drug’s market share with child/adolescent patients. The FDA repeatedly warned the company against promoting it for use in children. Janssen allegedly paid speaker fees to doctors to influence them to write prescriptions and told these doctors that if they wanted to receive payments for speaking, they needed to increase their Risperdal prescriptions. | 2013 | US$2.2 billion |
| Versatis/Lidoderm (lidocaine) | Grünenthal (UK), Endo (US) | Non-postherpetic neuralgia (PHN) | (1) Ad in the BMJ with claim “New for burning, shooting, stabbing pains” implied that Versatis was licensed to treat any such pain irrespective of its origin, when in fact the drug was only licensed for PHN. (no. 1960/2/07). (2) See Table 1 case no. 2330/7/10. | 2007, 2010 | £2,500, £2,500 | From March 1999 through December 2007, Endo promoted Lidoderm for use in the treatment of non PHN-related pain. Allegations that sales managers provided instruction to sales representatives concerning how to expand sales conversations with doctors to off-label uses. Endo admitted that it intentionally promoted Lidoderm to health care providers for unapproved indications. | 2014 | US$193 million |
| Botox (botulinum neurotoxin) | Allergan | Headache (HA), etc. | (1) Product monograph and objection handler contained claim that Botox was “… approved in over 70 countries, with 20 licensed indications.” The PMCPA considered that although both documents listed the six indications approved in the UK, reference to the 20 licensed indications worldwide might solicit questions about indications not licensed in the UK. (no. 2215/3/09). (2) A survey headed “Neurology Pharmaceutical Survey” together with a check for £35 was sent by a market research agency. Six of the 22 questions referred to the use of botulinum injections for the treatment of primary HA or migraine, which were off-label uses. The PMCPA considered that the survey would stimulate interest in the off-label use of Botox. Upon reading the report, the MHRA concluded that the survey and associated payment breached advertising regulations by promoting Botox off-label and offering doctors a prohibited benefit. Allergan agreed to issue corrective statement to recipients of survey and check. The MHRA deemed it in public interest not to pursue doctors who had accepted the payment in good faith but asked them to donate the money to charity, (no. 2274/10/09). | 2009, 2009 | £5,000, £2,500 | Allergan plead guilty to allegations of off-label promotion for HA, pain, spasticity, and juvenile cerebral palsy. The allegation was that Allergan exploited its on-label cervical dystonia (CD) indication to grow off-label pain and HA sales. In 2003, Allergan developed the “CD/HA Initiative” as a “rescue strategy” in the event of negative results from its clinical trials to ensure continued expansion into the pain and HA markets. As part of this initiative, Allergan claimed that CD was “underdiagnosed” and possible to diagnose based on HA and pain symptoms, even when the doctor “doesn’t see any.” Allergan’s marketing tactics also included calling on doctors who typically treat patients with off-label conditions and assisting doctors in obtaining reimbursement for off-label uses. Allergan held workshops to teach doctors and their office staffs how to bill for off-label uses, conducted detailed audits of doctors’ billing records to demonstrate how they could make money by injecting Botox, and operated the Botox Reimbursement Hotline, which provided free on-demand services to doctors for off-label uses. Allergan also lobbied government health care programs to expand coverage for off-label uses, directed physician workshops and dinners focused on off-label uses, paid doctors to attend “advisory boards” promoting off-label uses, and created a purportedly independent online education organization to stimulate off-label use. | 2010 | US$600 million |
1 Summaries based on DOJ press releases: http://www.justice.gov/.
2 May include both civil settlements under the FCA and criminal settlements. May also include settlements for illicit activities other than off-label promotion.
3 The settlement also included illicit promotion of other drugs.
4 Settlement for COPD part. Settlement for Asthma part was US$686 million.