AUTH/2830/3/16 - Pharmacosmos v Vifor

Promotion of Ferrinject

  • Received
    31 March 2016
  • Case number
  • Applicable Code year
  • Completed
    07 December 2016
  • Breach Clause(s)
  • Sanctions applied
    Undertaking received
  • Additional sanctions
  • Appeal
    Appeal by respondent
  • Review
    February 2017 Review

Case Summary

Pharmacosmos alleged that Vifor's promotion of Ferinject (ferric carboxymaltose for injection/ infusion) represented a clear and national pattern of misleading and disparaging claims about the safety profile of its product, Monofer (iron isomaltoside). Both medicines were for the treatment of iron deficiency when oral iron was ineffective or could not be used. 

Pharmacosmos noted that there were no comparative efficacy or safety studies for Monofer and Ferinject. Further, a review of all medicines in the same class by the European Medicines Agency (EMA) concluded that there were no meaningful differences in the safety profiles of the available products. 

Pharmacosmos stated that many of the issues that it had raised with Vifor in inter-company dialogue stemmed from comments made to it by health professionals. The health professionals were reluctant to be named and so it was difficult to substantiate their allegations. Pharmacosmos had recently raised six new examples with Vifor which it stated supported its position. Pharmacosmos recognised that the examples were anecdotal but that for clarity it had not made specific allegations for each one but wished to portray them as part of the overall picture to give credence to its concerns of a pattern of disparaging comments. 

Pharmacosmos stated that although Vifor consistently denied inappropriate activity, it had made several commitments during inter-company dialogue including an agreement to brief all employees about the use of certain documents and the nature of discussions regarding the adverse events profile of Ferinject and Monofer. Unfortunately, however, a report from one health professional led Pharmacosmos to question the integrity of Vifor's commitments.

Pharmacosmos drew particular attention to an additional report it had received about a medical information email sent by Vifor to a named hospital specialist nurse who stated that she did not request the letter. The letter referred to a report from a pharmacovigilance body in the Netherlands; Pharmacosmos queried whether the UK nurse would know about or request such a report. Pharmacosmos noted that the medical information letter stated that a representative had asked for the report to be sent. Pharmacosmos alleged that Vifor had provided the information proactively and that as this was one example of a representative disparaging Monofer, it was likely that the other cited examples of disparagement were also true. Pharmacosmos stated that an appraisal of Vifor's representatives' training material would corroborate its concerns because it was likely to link the dextran derived nature of the Monofer molecular structure to a higher (alleged) propensity for adverse events. Further, the nurse's experience referred to above raised doubts about the quality of investigations undertaken by Vifor and the effectiveness of the direction given to representatives with regard to comparing product safety profiles in response to concerns raised in inter-company dialogue. 

Pharmacosmos alleged that Vifor had misled health professionals by implying there was a difference in the safety profiles of Monofer and Ferinject when no formal comparison between the two existed. The consistent and widespread pattern of comments from health professionals indicated that, on the balance of probability, Vifor representatives had proactively raised the safety profile of Monofer in order to imply differences between the products. Pharmacosmos referred to the six recent examples. 

Pharmacosmos concluded that whilst it had hoped that Vifor had adequately and appropriately addressed the six alleged cases of disparaging and misleading claims highlighted during inter-company dialogue, it was shocked and concerned to learn that this activity had continued, as outlined in the nurse's first-hand account. Anxiety of clinical staff could increase the incidence of adverse events and given the nature of Vifor's alleged activities this was likely to have a direct impact on staff's confidence with Monofer and therefore put patients' lives at risk. 

Pharmacosmos stated that the referenced incidents of alleged disparaging and misleading claims by Vifor representatives had all been raised verbally to Pharmacosmos by health professionals in the UK and Ireland. To provide further context to what and how the information was shared with Pharmacosmos the relevant members of the Pharmacosmos team were asked to provide written statements, copies of which were provided. For completeness, Pharmacosmos provided statements to each case referenced in its complaint and noted that it had anonymised the names of the health professionals as it did not have their permission to identify them. Pharmacosmos further stated that it was its interpretation that 'information from [named] Hospital' related to Grant et al (2013) that described a local hospital audit of Monofer. 

The detailed response from Vifor is given below. 

The Panel noted Pharmacosmos' allegation that Vifor representatives had disparaged Monofer and provided misleading information about Monofer safety by implying there was a difference in the safety profiles of Monofer and Ferinject when no formal comparison between the two products existed. Pharmacosmos provided six anecdotal examples and Vifor responded to each with specific details. The Panel did not consider these examples per se when making its ruling as Pharmacosmos had not made specific allegations for each example but had cited them to substantiate its concerns of a pattern of disparaging comments.

The Panel noted that in addition Pharmacosmos provided a medical information email it alleged was sent proactively (not in response to a request) by Vifor to a specialist nurse at a named hospital as evidence that Monofer had been disparaged. The medical information email was the subject of Case AUTH/2828/3/16. The medical information email stated:


'Thank you for your enquiry on Ferinject (ferric carboxymaltose: FCM). I understand from my colleague, [named], that you have requested a copy of the Lareb report. 

The Netherlands Pharmocovigilance Centre, Lareb, has received concerns from multiple Dutch hospitals in relation to iron isomaltoside after the switch from iron carboxymaltose (FCM). Doctors and nurses reported an increase in the severity and incidence of allergic reaction. The report has not mentioned any specific safety concerns with FCM.' 


The Panel noted that the latter statement was untrue as the report detailed 7 reports of hypersensitivity/anaphylactic reactions associated with the use of Ferinject.

The Panel noted Pharmacosmos' disbelief that a typical UK health professional would know about the Lareb report, which was a specific pharmacovigilance assessment of Monofer made by the Dutch pharmacovigilance authority. Pharmacosmos had also submitted that it was difficult to understand why a health professional would proactively request a copy of that report Pharmacosmos considered the provision of the Lareb report most likely occurred following a representative visit which included comments about the safety profile of Monofer. 

The Panel noted Pharmacosmos' statement that an appraisal of material used to train Vifor representatives would corroborate its concerns because it was likely to draw attention to Monofer's adverse event profile. 

The Panel noted Vifor's submission that during initial training, representatives were briefed not to discuss competitor products in detail beyond the SPC. This briefing included the instruction that for non-Vifor products, representatives had to refer a customer to the product's SPC. The Panel noted Vifor's submission that the Intravenous Iron Differentiator tool and the SPC Comparator were the only materials available to the representatives that mentioned Monofer. Otherwise the customer was advised to contact the medical information department of the product market authorization holder. 

The Intravenous Iron Differentiator tool was a slide set which specifically differentiated Ferinject from Monofer and which was according to its briefing material designed to be used proactively in threatened accounts that were considering switching to Monofer and in accounts that had switched to Monofer. Two slides specifically compared the side-effects and contraindications of Ferinject and Monofer. The briefing regarding these two slides referred to confidence with Ferinject and in that regard implied a lack of confidence with Monofer. The briefing material stated, in summary, that 'The Ferinject proposition is strong, be confident, we have the best treatment'. In the Panel's view the briefing material was at odds with Vifor's submission that it did not permit representatives to discuss comparative safety in a promotional environment. The Panel noted Vifor's submission that the slide on the comparison of dosing was based on the relevant products' SPCs. The Panel noted that the slide also stated that the way in which the Monofer dose was calculated (the Ganzoni formula) was 'inconvenient, prone to error, inconsistently used in clinical practice, and it underestimates iron requirements'. The briefing on this slide referred to Ganzoni-based dosing as being problematic. 

A briefing document approved in January 2016 (Questions and Answers. Reactive responses to competitor messages, listed the comments and messages from customers regarding Monofer and stated 'What we need to do is reactively discuss the FACTS in an accurate and balanced way, to allow the customer to make an informed decision'. It was stated on one slide that one of the benefits of Ferinject, in an implied comparison with Monofer, was confidence because it was the market leader. The document included an explanation that the misconception of the competitor claim 'Reformulation, old Monofer had [adverse events], new formulation is better' suggested that Pharmacosmos acknowledged Monofer had a problem with adverse events as the only reformulation Vifor was aware of was Diafer which was simply half strength Monofer. The final message of the briefing document was again 'The Ferinject proposition is strong, be confident, we have the best treatment'. 

In the Panel's view, there was no doubt that Vifor was specifically targeting Monofer sales and that the representatives had been briefed to discuss the comparative safety of Ferinject vs Monofer. 

The Panel noted Vifor's submission that Grant et al was included with an overview of all relevant papers in the 'Clinical papers' session of the initial training course. Vifor noted that the aim of including that information was to educate Vifor employees on the place Ferinject's data held within the broader context of other products. The emphasis was on Ferinject and representatives were instructed not to use the competitor data with customers unless the data contained information on a Vifor product. 

The Panel noted Vifor's explanation that Grant et al was published as an abstract in Gut in September 2013. Grant et al was an audit of case notes of 40 patients who had received Monofer. The authors concluded 'Utilisation of Monofer in our clinical practice has shown a sub-optimal attainment of Hb target. Furthermore, the frequency of adverse reactions was much higher than expected from those reported in the product SPC or previous studies in renal patients. In light of these observations we no longer use Monofer'. 

A medical update was provided at the December 2013 sales conference which included information on recent publications for Ferinject and Monofer and included, inter alia, Grant et al and the authors' conclusion as stated above. The slide set for the session stated on the first slide that it was for internal use for training purposes. The cover slide did not state, as submitted by Vifor that the training session was for information only. The Panel considered that the slides contained material which Vifor would expect its representatives to use. No context had been given to the results from Grant et al. 

The Panel disagreed with Vifor's submission that it only included safety information relating to Ferinject and Monofer in the Q&A document given that such comparisons appeared in the Intravenous Iron Differentiator tool and in the SPC Comparator tool. With regard to the latter, the Panel noted that the Ferinject and Monofer SPCs were being used by Vifor for a promotional purpose. The Panel noted that the briefing material stated that the tool had been designed to help representatives to directly compare different sections of the SPCs for the most prescribed IV irons including Ferinject and Monofer, it was to be used when asked specific questions about Vifor intravenous (IV) irons and those of its competitors. The briefing also stated that 'You can also project this from your iPad for use with multiple [healthcare professionals] at meetings'. There was no information on how to use the information provided in the tool and how to present the comparisons to a customer. The Panel noted Vifor's submission that representatives were briefed not to discuss competitor products in detail beyond the SPC. In the Panel's view, providing a tool which directly compared SPCs, implying that such direct comparisons of data were valid, went beyond that. The Panel also considered that the SPC Comparator tool went beyond the reminder given in December 2015 that representatives were not to discuss the safety of competitor products and that if a customer requested comparative safety data the request should be forwarded to medical information. 

​The Panel considered that on the balance of probabilities, given the strident tone and content of the sales materials and briefings, Vifor representatives had disparaged Monofer in promotional calls as alleged. The Panel further considered that on the balance of probabilities, Vifor representatives had provided misleading information with regard to the safety of Monofer as alleged. Breaches of the Code were ruled which were upheld on appeal from Vifor.