FDA awards grant to study generic transplant drug tacrolimus

The US Food and Drug Administration (FDA) has awarded a federal grant worth US$2.3 million to researchers at the University of Cincinnati, Ohio, USA, in order to continue studies into tacrolimus, a drug commonly used to stop rejection in transplant patients.

The grant has been awarded to the research group led by Professor Rita Alloway, Research Professor of Medicine and Director of Transplant Clinical Research at the University of Cincinnati, Department of Internal Medicine. The three-year grant will enable the group to carry out both retrospective and prospective trials studying the brand-name immunosuppressant Prograf (tacrolimus) compared to generic versions of tacrolimus in high-risk transplant patients.

Tacrolimus is an immunosuppressive drug that is used after organ transplant to reduce the activity of the patient’s immune system and so lower the risk of organ rejection.

Astellas Pharma manufactures the brand-name version of the drug, Prograf. Generics of tacrolimus have been available in the US since 2009 and there are currently six tacrolimus oral tablet generics approved by FDA. To date there are no injectable generics of tacrolimus approved in the US. In Europe, Astellas Pharma markets tacrolimus under the brand name Advagraf and Modigraf. No generics have yet been approved centrally by the European Medicines Agency (EMA), although in October 2013 the agency was reviewing an application for a generic version of the drug [1]. However, tacrolimus oral tablet generics have been approved at a national level in several EU countries.

Generic forms of tacrolimus are currently dispensed to more than 70% of transplant patients. ‘The largest concern for clinicians is the switchability between various generics,’ says Professor Alloway. ‘When patients receive their prescription, they could be getting medication from different manufacturers each month.’

These studies aim to address these concerns. In the retrospective study, transplant recipients will be assessed for variability one year prior and one year post-conversion to generic tacrolimus. Evaluations will include incidence of rejection, hospital admission, changes in renal function and changes in transplanted organ function. The prospective study will compare the relative bioavailability and steady-state pharmacokinetics of six tacrolimus formulations in a prospective, 6-way crossover study. The study will include 30 transplant patients expressing the CYP3A5 enzyme and 30 non-expressor transplant patients. CYP3A5 expressors have been shown to require larger doses of tacrolimus to attain therapeutic blood concentrations. This study design comparing all tacrolimus formulations in CYP3A5 expressors and non-expressors was based upon preliminary data which suggests that CYP3A5 expressors may exhibit greater variability in C_max than non-expressors.

In 2012, Professor Alloway also received a US$2.7 million grant from FDA to study whether the two most disparate generic versions of tacrolimus are bioequivalent to the brand-name version of the drug in stable transplant patients [2].

The results of these studies are expected to address public concerns regarding the use of generic tacrolimus.

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Source: www.gabionline.net