AUTH/2841/4/16 - Anonymous, non contactable v GlaxoSmithKline

Promotion of Anoro Ellipta

  • Received
    25 April 2016
  • Case number
    AUTH/2841/4/16
  • Applicable Code year
    2015
  • Completed
    03 November 2016
  • No breach Clause(s)
    2, 3.2, 7.2, 9.1
  • Breach Clause(s)
    3.2, 7.2 (x2), 9.1
  • Sanctions applied
    Undertaking received
  • Additional sanctions
  • Appeal
    appeal by respondent
  • Review
    November 2016 Review

Case Summary

​An anonymous, non contactable complainant complained about the promotion of long-acting beta agonist/long-acting muscarinic antagonists (LABA/ LAMA) combination inhalers for the treatment of chronic obstructive pulmonary disease (COPD). The complainant referred to the first medicine to be licensed within this class, Ultibro Breezhaler (indacaterol maleate and glycopyrronium bromide) noting that it was clear from its European Public Assessment Report (EPAR) that the Committee for Medicinal Products for Human Use (CHMP) turned down an application that included its use to reduce COPD exacerbations, because its effects in that regard were too small to recommend such use. Ultibro Breezhaler was subsequently licensed only as a maintenance bronchodilator treatment to relieve symptoms in adults with COPD and thus its promotion in relation to COPD exacerbation reduction was off-label. The complainant cited other examples of what could be considered to be off-label promotion based on the CHMP ruling on LABA/LAMA combination inhaler indications and in that regard noted, inter alia, GlaxoSmithKline's product Anoro Ellipta (vilanterol/umeclidinium) for which, according to its EPAR, a specific licence for exacerbation reduction was never applied for.

Anoro was indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD.

In relation to this case the complainant noted in particular that a MIMS webpage which reviewed Anoro Ellipta included the claim that COPD exacerbations were reduced by 50% compared with placebo. The complainant submitted that the item contained no information warning of the off-label aspects of the promoted use of the product.

The complainant concluded that as there was no specific indication for exacerbation reduction in the registration applications for Anoro Ellipta, the medicine was not licensed for use to reduce exacerbations in COPD patients and so promoting it to reduce COPD exacerbation reduction was off-label.

The complainant stated his/her colleagues had little awareness that LABA/LAMA combination inhalers or LAMA inhalers were being prescribed in an unlicensed manner. Also, formal recommendations for the use of these medicines in exacerbation reduction were increasingly appearing in local clinical guidelines which suggested that promotion of the medicines had not clearly communicated the off-label nature of this use. The complainant stated that the materials for the various inhalers to which he/she had drawn attention were just the tip of the iceberg; he/she knew of numerous educational meetings/symposia involving external speakers where exacerbation reduction data had been presented as part of product promotion.

A potential major concern for the complainant and his/her colleagues was that they might have unknowingly prescribed LABA/LAMA combination inhalers or LAMA inhalers to numerous COPD patients assuming that they were licensed for exacerbation reduction. The statement from the CHMP which considered exacerbation was therefore a sobering thought especially if COPD patients subsequently suffered exacerbations unexpectedly because their prescribed LABA/LAMA combination inhalers might not be effective enough as intimated by the CHMP assessment of Ultibro Breezhaler. COPD was characterised in part by airway inflammation and the extent of inflammation was progressive leading up to an exacerbation. None of the medicines in question contained an anti-inflammatory component. Another very important consideration was that prescribers were unaware from a medico-legal perspective that they would be solely liable for any adverse consequences suffered by patients which might arise.

The detailed response from GlaxoSmithKline is given below.

The Panel noted that Section 5.1 of the Anoro Ellipta summary of product characteristics (SPC) referred to its positive impact on exacerbations of COPD. The Panel noted that Section 1.1 of the National Institute for Health and Care Excellence (NICE) Guideline on the management of COPD listed the symptoms of the disease which were, inter alia, exertional breathlessness, chronic cough, regular sputum production and wheeze. In Section 1.3 of the Guideline, the exacerbation of COPD was described as a sustained worsening of the patient's symptoms from their usual stable state which was beyond normal day-to-day variations and was acute in onset. In the Panel's view, there was a difference between COPD symptoms and exacerbations of COPD although it accepted that patients whose symptoms were well controlled might be less likely to experience an exacerbation of their condition than patients with poorly controlled symptoms. In that regard the Panel considered that exacerbations might be referred to in the promotion of COPD maintenance therapy but that there was a difference between promoting a medicine for a licensed indication and promoting the benefits of treating a condition. In the Panel's view, reference to reduced COPD exacerbation must be set within the context of the primary reason to prescribe ie maintenance therapy to relieve symptoms.

The Panel noted that Anoro Ellipta was first authorised on 8 May 2014. The MIMS article referred to by the complainant was dated 24 June 2014 and headed 'In Depth – Anoro Ellipta: first LABA/LAMA combination inhaler for COPD'. The Panel noted GlaxoSmithKline's submission that it did not commission the MIMS article nor did it have any editorial control over it. The company submitted that it had no awareness of its inception or publication. GlaxoSmithKline had received confirmation from the editor that MIMS articles were produced independently. The Panel considered that as the article at issue was wholly independent of GlaxoSmithKline, it did not come within the scope of the Code and no breach was ruled in that regard.

The Panel did not consider that either the primary care iPad presentation and its accompanying briefing material, nor other material, promoted Anoro Ellipta for the reduction of COPD exacerbation as alleged. Reference to exacerbations had been presented within the context of the licensed indication ie as a benefit of therapy and not the reason to prescribe per se. The Panel considered that the promotion of Anoro Ellipta had been consistent with the particulars listed in the SPC. The materials did not misleadingly imply that exacerbation reduction was a primary reason to prescribe Anoro Ellipta. Briefing materials did not present exacerbation data in such a way as to advocate a course of action which was likely to breach the Code. High standards had been maintained. No breaches of the Code were ruled.

The Panel noted that it had also been provided with copies of three certified presentations delivered by health professionals on behalf of GlaxoSmithKline. Slide 12 of a presentation entitled 'COPD – Latest therapies' stated that one of the aims of treatment was to reduce symptoms and increase the patient's quality of life and also to reduce exacerbations/ admissions and mortality. Slide 36, headed 'Exacerbations', stated, inter alia, that Anoro produced a 50% reduction in time to first exacerbation vs tiotropium. Slide 55 clearly stated the licensed indication for Anoro ie maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. The following, and last 9 slides detailed clinical results for Anoro and gave a brief overview of the medicine. Reduction of exacerbations was not referred to on these slides. On balance, and notwithstanding one brief mention of exacerbation reduction in a set of 65 slides, the Panel did not consider that overall the presentation promoted Anoro for exacerbation reduction. No breach of the Code was ruled. The Panel, however, considered that the claim about reduced time to first exacerbation was misleading given GlaxoSmithKline's submission that clinical studies were not designed to evaluate the effect of Anoro on COPD exacerbations. A breach of the Code was ruled.

A second presentation about breathlessness in COPD, included a number of slides specifically about Anoro including one which referred to exacerbation data from a study comparing Anoro with tiotropium. The licensed indication for Anoro was not clearly stated anywhere in the presentation. Similarly, the final presentation 'Management and prevention of exacerbations of COPD', gave an overview of COPD, the effects of exacerbations on patients and the role of treatment in acute exacerbation. One slide headed 'LAMA-LABA' stated that Anoro reduced COPD exacerbations by 50% vs placebo and also vs tiotropium. Nowhere in the presentation was the licensed indication of Anoro stated. The Panel considered that in the absence of any statement to the contrary, some viewers might assume that Anoro could be prescribed per se to reduce COPD exacerbations for which the medicine was not licensed. In that regard the Panel considered that the presentations were not consistent with the particulars listed in the SPC. A breach of the Code was ruled which was upheld on appeal by GlaxoSmithKline. The Panel considered that although Anoro exacerbation data could be referred to, it was misleading to do so when the licensed indication for the medicine had not been clearly stated and there was no statement to the effect that clinical studies were not designed to evaluate the effect of Anoro on COPD exacerbations. A breach of the Code was ruled.

With regard to the three presentations, the Panel noted its rulings of breaches of the Code above and considered that high standards had not been maintained. A further breach of the Code was ruled.

The Panel noted its rulings and comments above about the presentations but considered that the matters were not such as to bring discredit upon, or reduce confidence in, the industry. No breach of Clause 2 was ruled.