AUTH/3460/1/21 - Complainant v Novartis

Promotion of Beovu

  • Received
    21 January 2021
  • Case number
  • Applicable Code year
  • Completed
    24 August 2021
  • No breach Clause(s)
  • Additional sanctions
  • Appeal
    No appeal

Case Summary

A contactable complainant who later became non-contactable and who described him/herself as a health professional was concerned about the lack of safety information given in a journal advertisement (ref BRO20 – C053, November 2020) for Beovu (brolucizumab) placed in the December 2020 issue of the British Journal of Ophthalmology by Novartis Pharmaceuticals UK.

Beovu was presented as a pre-filled syringe for intravitreal injection, for use in adults for the treatment of neovascular (wet) age-related macular degeneration (nAMD).

The advertisement in question was headed ‘For adults with wet AMD, their vision is a masterpiece’ and included four claims for Beovu which were attributable to the HAWK and HARRIER trials. The first three claims were about the efficacy of Beovu and the fourth stated that in HAWK and HARRIER Beovu ‘Exhibited an overall well-tolerated safety profile in treated patients.’

The complainant submitted that Beovu had been the subject of serious, sight-threatening complications which were noted in the pivotal trials, acknowledged as a safety signal by Novartis, and were subject to a mandated summary of product characteristics (SPC) update. The complainant considered that it was irresponsible to promote Beovu without providing safety information; it was worrying, misleading and risked patient safety.

The detailed response from Novartis is given below.

The Panel noted that the advertisement was placed in the British Journal of Ophthalmology and that the Beovu SPC stated that Beovu must be administered by a qualified ophthalmologist experienced in intravitreal injections. The Panel noted that this was a very specialist area.

The Panel noted that the complainant made no reference to any of the claims but was concerned about the lack of safety information in the advertisement given the serious, sight-threatening complications that had been noted with Beovu. The Panel noted Novartis’ submission that adverse events of retinal vasculitis and/or retinal vascular occlusion were first seen in post-marketing reports and not in the pivotal trials as submitted by the complainant. A review of the post-marketing cases, with a comparison of inflammatory adverse events seen in the Beovu Phase 3 trials (HAWK and HARRIER) confirmed the safety signal. The Panel noted Novartis’ submission that following confirmation of the signal, it informed all relevant health authorities globally; neither the Medicines and Healthcare products Regulatory Agency (MHRA) nor the European Medicines Agency (EMA) expedited processes or asked for further actions beyond the standard processes for safety notifications and label updates. In October 2020, the EMA approved an update to the Beovu SPC, sections 4.4 (special warnings and precautions) and 4.8 (undesirable side effects), with no special conditions or requirements as part of its marketing authorisation. The Panel noted that the SPC stated that the frequency of retinal vascular occlusion and retinal vasculitis was ‘not known’.

The Panel considered that it was not necessarily unacceptable not to include detailed safety data in an advertisement as long as the material complied with the Code and was not misleading in that regard. Material must not be inconsistent with the particulars in a medicine’s current SPC. The Panel considered that whether specific safety data needed to be highlighted in promotional material, in addition to that which was required to be included within the prescribing information, depended on a consideration of all of the circumstances including the nature of the information, the therapy area and the content, context and layout of the material. The intended audience was also a relevant factor.

The Panel noted that the prescribing information at the base of the advertisement stated, under ‘Warnings/Precautions’, that retinal vasculitis and/or retinal vascular occlusion had been reported, typically in the presence of intraocular inflammation and that patients should be instructed to report any relevant symptoms without delay. The prescribing information also included ‘retinal vascular occlusion’ and ‘retinal vasculitis’ under the ‘Undesirable effects’ section with the frequency being unknown. The Panel further noted Novartis’ submission that the prescribing information contained all relevant information for prescribers and there was no requirement to specifically address individual warnings or precautions, beyond inclusion in the prescribing information, particularly as there were no special/restricted conditions of use imposed by the EMA within the marketing authorisation and/or the SPC.

The Panel noted that the only claim in the body of the advertisement with regard to safety was ‘In HAWK & HARRIER, Beovu Exhibited an overall well-tolerated safety profile in treated patients’. The HAWK and HARRIER studies compared the safety and efficacy of Beovu vs aflibercept and in a post hoc analysis of the pivotal trials, a Novartis commissioned review noted that despite the vision loss associated with increased incidences of intraocular inflammation, retinal vasculitis and/or retinal vascular occlusion associated with Beovu, the overall rates of at least moderate vision loss were similar between the Beovu and aflibercept treatment arms (7.4% vs 7.7% respectively). The Panel noted that the post hoc review of HAWK and HARRIER (Monés et al, 2020) stated that it was critical that physicians appropriately monitored Beovu patients for this safety signal and that the findings would help to evaluate the risks and benefits of Beovu treatment. The Panel further noted Novartis’ submission that the authors of the peer-reviewed HAWK and HARRIER manuscript (Dugel et al, 2021), which was published after post-marketing reports of retinal vasculitis and/or retinal vascular occlusion, stated that ‘although numerical differences were found in some adverse events and serious adverse events ... brolucizumab exhibited an overall well-tolerated safety profile’.

The Panel noted that the National Institute for Health and Care Excellence (NICE) was aware that Beovu’s SPC noted a risk of retinal vasculitis and retinal vascular occlusion. The evidence review group explained that because these adverse events were rare, it was not likely to affect the view that the overall impact on health of those associated with brolucizumab were similar to those of aflibercept and ranibizumab. The committee concluded that adverse events with brolucizumab were likely to be similar to aflibercept and ranibizumab.

The Panel considered that in the particular circumstances of this case, given the very specialist therapy area and the experience that prescribing opthalmologists would have with intravitreal injections, the advertisement did not imply that there were no safety concerns with Beovu. In the Panel’s view, the complainant had not established that it was misleading to have not included additional safety data in the body of the advertisement. The Panel did not consider that the advertisement was misleading as alleged and did not consider that the complainant had established that the advertisement did not encourage the rational use of Beovu. No breaches of the Code were ruled.

The Panel noted its comments and rulings above and considered that the complainant had not shown that high standards had not been maintained. No breaches of the Code were ruled including of Clause 2.