AUTH/3465/2/21 - Complainant v Vifor

Alleged off-licence promotion of Venofer

  • Received
    01 February 2021
  • Case number
    AUTH/3465/2/21
  • Applicable Code year
    2019
  • Completed
    25 August 2021
  • No breach Clause(s)
  • Additional sanctions
  • Appeal
    No appeal

Case Summary

An anonymous, contactable complainant, who described him/herself as a concerned UK health professional, alleged that use of the PIVOTAL study by Vifor Pharma UK Limited to promote Venofer (iron sucrose for intravenous (IV) administration) promoted its off-licence use. The complainant referred to a sponsored symposium. Venofer was indicated for, inter alia, the treatment of iron deficiency in chronic kidney disease when oral therapy was less effective.

The complainant provided a link to a Vifor sponsored symposium entitled ‘High dose proactive intravenous iron treatment in ESKD [end-stage kidney disease] – sub-analysis of the PIVOTAL study’. The 15-minute symposium took place in October 2020.

The complainant stated that the PIVOTAL trial used Venofer in patients proactively, rather than using its licensed indication.

The complainant noted that the Venofer licence stated:

‘Venofer is indicated for the treatment of iron deficiency in the following indications:

• Where there is a clinical need for a rapid iron supply,

• In patients who cannot tolerate oral iron therapy or who are non-compliant,

• In active inflammatory bowel disease where oral iron preparations are ineffective,

• In chronic kidney disease when oral iron preparations are less effective.

The diagnosis of iron deficiency must be based on appropriate laboratory tests (e.g. Hb, serum ferritin, TSAT, serum iron, etc.).
(Hb haemoglobin, TSAT transferrin saturation).’

The complainant stated that in the trial, patients did not have to have iron deficiency to receive treatment, they merely did not receive treatment if there was a raised ferritin level. The complainant alleged that to use the PIVOTAL trial was highly likely to promote Venofer off-licence since the entire design of the trial was off-licence.

The detailed response from Vifor is given below.

The Panel noted that according to the Venofer SPC, one of the licensed indications for the medicine was in the treatment of iron deficiency in chronic kidney disease when oral iron preparations were less effective, with the diagnosis of iron deficiency being based on appropriate laboratory tests (eg Hb, serum ferritin, TSAT, serum iron, etc.). The SPC did not specify what test values were required for the diagnosis of iron deficiency.

The Panel noted the complainant’s concern that patients in the PIVOTAL study did not need to have iron deficiency, they merely did not receive treatment if there was a raised ferritin level. The Panel noted that patients in the high-dose, proactive treatment arm all received Venofer unless they had raised ferritin levels (>700μg per litre) or a TSAT score of ≥40%; for those in the low-dose arm, reactive treatment, Venofer therapy was appropriate for patients with ferritin levels of <200μg per litre and a TSAT score of <20%.

With regard to ferritin levels, the Panel noted that the Guidelines for the Laboratory Diagnosis of Functional Iron Deficiency stated that in CKD patients on haemodialysis, ferritin levels of up to 800µg per litre were consistent with a diagnosis of iron deficiency and that ferritin values up to 1200µg per litre did not exclude the possibility of functional iron deficiency and that some such patients might respond to IV iron therapy. An algorithm for the management of CKD patients stated that haemodialysis patients with ferritin levels of <200μg per litre had classical iron deficiency (ie those in the low dose arm of the PIVOTAL study) and that haemodialysis patients with ferritin levels >200µg per litre but <800µg per litre had functional iron deficiency (ie the patients in the high dose arm of the study).

With regard to TSAT levels, the Panel noted that the guidelines referred to above stated that values of <20% indicated the need for parenteral iron in the setting of anaemia treated with erythropoiesis stimulating agents but that used in isolation, TSAT had poor sensitivity and specificity in detecting those who would respond to IV iron.

Overall, the Panel did not consider that the complainant had shown that the use of Venofer in the PIVOTAL study was off-licence; it appeared to the Panel that the use of Venofer was in line with the indication as set out in the SPC and complied with the current, clinically accepted definition of iron deficiency in haemodialysis patients. No breaches of the Code were ruled including Clause 2.