摘要:

Priliximab (Anti-CD4 MAb, CEN 000029, MT 412, cMT 412) is a chimeric anti-CD4 monoclonal antibody constructed from the antigen-binding variable region of the murine CD4 antibody M-T412 and the constant region of the human IgG1 kappa immunoglobulin. Priliximab retains the same high affinity, epitope specificity and ability to down regulate T-helper-inducer function as a pure murine CD4 Ab.It is under development with Centocor (as Centara®) and is in phase I/II clinical trials in the Netherlands and the US for use in Crohn's disease and in Germany for early heart transplant rejection, and phase I clinical trials in the US for the treatment of patients with cutaneous CD4+ T cell lymphoma. Priliximab has shown beneficial effects in patients with rheumatoid arthritis (RA). Clinical trials of priliximab for the treatment of RA are proceeding in the Netherlands and the US. The drug is also under phase II clinical investigation in the US and Europe for the treatment of multiple sclerosis.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;SDZ RAD (Rapamycin SDZ) is an orally active immunosuppressant analog of rapamycin, a macrolide antibiotic produced byStreptomyces hygroscopicus. It has been identified by Novartis, Switzerland, in an attempt to overcome the wide interindividual variation in pharmacokinetic properties observed with the oral administration of sirolimus (rapamycin). SDZ RAD is currently undergoing phase II clinical studies in Germany and phase I/II trials in Switzerland for the treatment of transplant rejection.Similar to sirolimus, its mechanism of action differs from that of both cyclosporin and tacrolimus, providing a rationale for synergism which has been extensively demonstrated.In addition to the mechanism of action, cyclosporin and sirolimus also differ in their respective side effect profiles making sirolimus and its analogs very interesting compounds for clinical transplantation.SDZ RAD has been identified in the effort to overcome the formulation problems of sirolimus while retaining its pharmacological activities. Although there is a small loss in immunosuppressive activityin vitro, when orally administeredin vivoit is at least as efficient as sirolimus in preventing graft rejection in rat models of allotransplantation. Thus, this new sirolimus analog has the potential to confirm in clinical trials the promising results observed in preclinical studies.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Produced by the soil actinomyceteStreptomyces hygroscopicus, sirolimus (AY 22989, NSC 226080, NSC 606698, rapamycin, Rapamune®) is a macrolide antibiotic with potent immunosuppressant and antitumour activity.Sirolimus inhibits the proliferation of T and B cells and the proliferation of growth factor-dependent and -independent non-immune cells. Unlike cyclosporin and tacrolimus, which block Ca++-dependent cytokine transcription early in G1 phase thus inhibiting T cell activation, sirolimus inhibits proliferation of activated T cells by inhibiting cytokine-mediated signal transduction pathways later in G1 phase. Preclinical trials indicated that sirolimus is associated with reduced nephrotoxicity compared with cyclosporin. The therapeutic applicability of sirolimus will largely be decided by its safety and efficacy profile to be established during clinical trials.[1]Sirolimus is currently in phase III clinical trials with Wyeth-Ayerst (a subsidiary of American Home Products) in the USA, Australia, Belgium, Canada, France, Italy, Norway, Spain and Sweden as first-line chronic therapy for the prevention of acute renal transplant rejection and in phase II trials for prevention of liver, bone marrow and cardiac transplant in the USA. The drug is also in phase I clinical trials for the treatment of cancer and appears to be under preclinical development for the prevention of graft-versus-host disorders in bone marrow transplant recipients. Sirolimus also appears to be undergoing preclinical trials in the USA for the treatment of diabetes mellitus, asthma and rheumatic disorders. A phase II trial is being planned in the US to assess the safety and efficacy of sirolimus in patients with recalcitrant psoriasis. Sirolimus is no longer available for licensing.A nanoparticle formulation of sirolimus is to be developed and tested in late stage clinical trials as a result of a recent agreement between Wyeth-Ayerst and NanoSystems LLC. The patented NanoSystems' NanoCrystal® drug formulation technology will be applied in order to improve the bioavailability of the drug thus enhancing its clinical performance.Although structurally similar to tacrolimus, sirolimus acts on the immune system in a different manner. It is synergistic with cyclosporin allowing a sensible reduction of the doses of both drugs.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;SR 31747 is an interleukin-1 antagonist and peripheral opioid sigma receptor antagonist with immunosuppressant properties. It inhibits T cell proliferation and reduces interleukin-1, interleukin-6 and tumour necrosis factor production. SR 31747 is being developed by Sanofi (France), and is undergoing phase II clinical trials for the treatment of autoimmune disorders, rheumatoid arthritis and transplant rejection. It may also have potential for the treatment of psoriasis.SR 31747 is a structurally unique immunosuppressant which has a novel mechanism of action through its inhibition of sigma receptors of leucocytes. It selectively inhibits Th1 lymphocytes. The potential of this agent for the treatment of transplant rejection, autoimmune disorders and rheumatoid arthritis can be defined more clearly once clinical data are available.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;Tresperimus (LF 080299) is an analogue of the immunosuppressant 15-deoxyspergualin (gusperimus). It is under phase II clinical development with Groupe Fournier in France for use in organ transplant rejection and under phase II studies in Europe and US for graft-versus-host disorders.Groupe Fournier is actively seeking co-development and marketing partners in the US and Japan.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS