Novel immunosuppressive agents in kidney transplantation

Table 1 Summary of investigational and available agents

Generic	Brand	FDA indication	Company
Alefacept12	Amevive	Treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy	Astellas
Alemtuzumab2	Campath	Treatment of B-CLL	Berlex Laboratories
ASKP1240		Not FDA approved	Astellas
Azathioprine	Imuran	Adjunctive therapy in prevention of rejection of kidney transplants; management of active rheumatoid arthritis	Generic manufacturers
Basiliximab	Simulect	Prevention of acute rejection in kidney transplantation	Novartis
Belatacept	Nulojix	Prevention of acute rejection in renal transplant recipients	Bristol-Myers-Squibb
Bortezomib	Velcade	Treatment of multiple myeloma; treatment of relapsed or refractory mantle cell lymphoma	Millenium Pharmaceuticals
Cyclosporine	Neoral	Prevention of acute rejection in renal transplant recipients	Novartis
Eculizumab	Soliris	Treatment of PNH to reduce hemolysis and aHUS	Alexion Pharmaceuticals
Efalizumab12	Raptiva	Management of moderate to severe chronic plaque psoriasis in adults	Genentech
Everolimus	Afinitor, Zortress	Treatment of advanced renal cell cancer (Afinitor®); treatment of subependymal giant cell astrocytom associated with tuberous sclerosis (Afinitor®); treatment of advanced, metastatic or unresectable pancreatic neuroendocrine tumors (Afinitor®); prophylaxis of organ rejection in patients at low-moderate immunologic risk receiving renal transplants (Zortress®)	Novartis
Mycophenolate Mofetil	Cellcept	Prophylaxis of organ rejection concomitantly with cyclosporine and corticosteroids in patients receiving allogeneic renal cardiac, or hepatic transplants	Genentech
Mycophenolate Sodium	Myfortic	Prophylaxis of organ rejection concomitantly with cyclosporine and corticosteroids in patients receiving allogeneic renal transplantation	Novartis
Horse or Rabbit anti-thymocyte Globulin	Atgam or Thymoglobulin	Treatment of corticosteroid resistant rejection in kidney transplantation	Pfizer/Sanofi
Rituximab	Rituxan	Treatment of CD20-positive non-Hodgkin’s lymphomas ; Treatment of moderately- to severely-active rheumatoid arthritis in adult patients with inadequate response to one or more TNF antagonists; Treatment of Wegener’s granulomatosis; Treatment of microscopic polyangiitis	Genentech
Sirolimus	Rapamune	Prevention of acute rejection in renal transplant recipients	Pfizer
Sotrastaurin, AEB-0711		Not FDA approved	Novartis
Tacrolimus	Prograf	Prevention of acute rejection in renal transplant recipients	Astellas
Tacrolimus Prolonged Release	Astragraf XL	Preventing organ rejection in kidney transplant recipients, as combination therapy with mycophenolate mofetil and corticosteroids, with or without tasiliximab induction	Astellas
Tolfacitinib1	Xeljanz	Treatment of moderate to severe rheumatoid arthritis	Pfizer
Voclosporin		Not FDA approved	Isotechnika Pharma

¹No longer being investigated for transplantation;

²Withdrawn from United States Market. FDA: Food and Drug Administration; B-CLL: B-cell chronic lymphocytic leukemia; PNH: Paroxysmal nocturnal hemoglobinuria; aHUS: Atypical hemolytic uremic syndrome.

Table 2 Non-Food and Drug Administration approved/investigational agents and their mechanism

Drug name	Mechanism of action
Induction
Efalizumab1	Humanized antibody, CD11a/LFA-1
Alefacept1	Costimulation inhibitor, CD2 LFA3
Maintenance
Voclosporin, ISA247	Calcineurin inhibitor
Sotrastaurin, AEB0711	Protein kinase C inhibitor
Tofacitinib, CP-6905501	JAK 3 inhibitor
ASKP1240	Anti-CD40 monoclonal antibody
Treatment of Antibody Medicated Rejection
Bortezomib	Proteasome inhibitor
Eculizumab	Monoclonal antibody, C5 complement protein

¹No longer being investigated for transplantation.

Table 3 Clinical trials

Agent	Identifier	Study name	Start date
ASKP1240	NCT01780844	A Study to Assess the Efficacy and Safety of ASKP1240 in de Novo Kidney Transplant Recipients	February 2013
Voclosporin	NCT01586845	Safety and Efficacy Study of Voclosporin and Tacrolimus in Transplantation	March 2013
Prolonged Release Tacrolimus	NCT01294020	Study to Compare the Pharmacokinetics of Tacrolimus in Stable Pediatric Allograft Recipients Converted From Prograf® to Advagraf®	May 2011
Bortezomib	NCT01873157	Bortezomib in Late Antibody-mediated Kidney Transplant Rejection (BORTEJECT)	October 2013
	NCT01349595	Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation	December 2011
	NCT01842074	Desensitization With Bortezomib Before a Living Kidney Donation (VELDON)	January 2013
	NCT01502267	Desensitization Protocol for Highly Sensitized Patients on the Waiting List for Kidney Transplant	January 2010
	NCT00722722	The Impact of Velcade on Antibody Secreting Cells in Sensitized Renal Allograft Candidates	June 2008
Eculizumab	NCT01349595	Impact of Proteasome Inhibition on Anti-Donor HLA Antibody Production After Kidney Transplantation	December 2011
	NCT01327573	Eculizumab Therapy for Chronic Complement-Mediated Injury in Kidney Transplantation	March 2011
	NCT01095887	Eculizumab Added to Conventional Treatment in the Prevention of Antibody-mediated Rejection in ABO Blood Group Incompatible Living Donor Kidney Transplantation (ABOi)	March 2010
	NCT01403389	A Study of the Activity of Eculizumab for Prevention of Delayed Graft Function In Deceased Donor Kidney Transplant	August 2011
	NCT01567085	Safety and Efficacy Of Eculizumab In The Prevention Of Antibody Mediated Rejection (AMR) In Sensitized Recipients Of A Kidney Transplant From A Deceased Donor	May 2012
	NCT01106027	Dosing Regimen of Eculizumab Added to Conventional Treatment in Positive Crossmatch Deceased Donor Kidney Transplant	March 2010
	NCT01399593	Safety and Efficacy of Eculizumab to Prevent AMR in Living Donor Kidney Transplant Recipients Requiring Desensitization	September 2011