Do two intravenous iron sucrose preparations have the same efficacy?

Abstract

Background. Intravenous (i.v.) iron sucrose similar (ISS) preparations are available but clinical comparisons with the originator iron sucrose (IS) are lacking.Methods. The impact of switching from IS to ISS on anaemia and iron parameters was assessed in a sequential observational study comparing two periods of 27 weeks each in 75 stable haemodialysis (HD) patients receiving i.v. iron weekly and an i.v. erythropoiesis-stimulating agent (ESA) once every 2 weeks. Patients received IS in the first period (P1) and ISS in the second period (P2).Results. Mean haemoglobin value was 11.78 ± 0.99 g/dL during P1 and 11.48 ± 0.98 g/dL during P2 (P = 0.01). Mean serum ferritin was similar for both treatment periods (P1, 534 ± 328 μg/L; P2, 495 ± 280 μg/L, P = 0.25) but mean TSAT during P1 (49.3 ± 10.9%) was significantly higher than during P2 (24.5 ± 9.4%, P <0.0001). The mean dose of i.v. iron per patient per week was 45.58 ± 32.55 mg in P1 and 61.36 ± 30.98 mg in P2 (+34.6%), while the mean ESA dose was 0.58 ± 0.52 and 0.66 ± 0.64 μg/kg/week, respectively (+13.8%). Total mean anaemia drug costs increased in P2 by 11.9% compared to P1.Conclusions. The switch from the originator IS to an ISS preparation led to destabilization of a well-controlled population of HD patients and incurred an increase in total anaemia drug costs. Prospective comparative clinical studies are required to prove that ISS are as efficacious and safe as the originator i.v. IS.

First Asia-Pacific educational workshop on non-biological complex drugs (NBCDs), Kuala Lumpur, Malaysia, 8 October 2013

“…The fi rst was of the substitution of a follow-on iron sucrose product (Ferex, BMI Korea) for the originator (Venofer®, Vifor Pharma Ltd, Switzerland) in gynaecological patients that resulted in signifi cantly more adverse events and higher overall costs [2]. The second was of inferior therapeutic effects and increase in costs seen after substitution of the follow-on Fer Mylan for Venofer® in French renal dialysis patients [3]. Substitutions were both based on theoretical cost savings and the clinicians were not aware of the switch until after they observed the negative effects.…”

“…The adequacy of this regulatory approval process has been questioned because therapeutic non-equivalence and non-interchangeability of authorized follow-on IV iron sucrose products have been reported [2,3]. Therefore, authorities addressed the urgent need to defi ne best practices for nanosimilar approval and post-approval pharmacovigilance to maximize the chances that such follow-on products provide patients with non-inferior safety and clinical outcomes [4][5][6][7][8][9].…”

Complexity in the making: non-biological complex drugs (NBCDs) and the pharmacopoeias

“…ISSs in Europe received marketing authorization through the generic drug pathway, suggesting interchangeability. Clinical reports such as reported in [10], however, have recently shown that IS and ISSs may not have the same or similar effi cacy and safety profi le, and thus appear not to be interchangeable. A regulatory pathway, comparable to the one applied for biosimilars, is therefore currently discussed as mentioned above.…”

The regulator’s perspective: How should new therapies and follow-on products for MS be clinically evaluated in the future?

“…41 It was concluded that the follow-on product was not therapeutically equivalent to the reference iron-sucrose complex. 41 In addition, it was shown that the reference iron-sucrose preparation and its follow-on products had different effects on nitrosative stress, apoptosis, oxidative stress and biochemical and inflammatory markers in rats. 42 Therefore, on March 2011, the CHMP adopted a Reflection Paper on non-clinical studies for generic nanoparticle iron medicinal product applications.…”