摘要:

All the drugs appearing in the Adis Profile Summary table have been selected based on information contained inR&D InsightTM, a proprietary product of Adis International. As the emphasis ofDrugs in R&Dis on the clinical potential of new drugs, selection of agents for a full profile is based on the extensiveness of available data. Information on all drugs in clinical development, as identified fromR&D InsightTM, is included in the summary table. Information and/or profiles of agents in preclinical development may be included as appropriate.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

BTI 322 (Anti-CD2 monoclonal antibody, monoclonal antibody Lo-CD2-a, Lo-CD2-a) is a rat IgG2b &kgr; anti-CD2 monoclonal antibody that binds specifically to the CD2 antigen receptor on T cells and NK cells, thereby suppressing their function. Currently, the drug is being codeveloped by BioTransplant and MedImmune after the 2 companies formed a strategic alliance to develop products for the prevention and treatment of organ transplant rejection.A phase I/II clinical trial has been completed for the prevention and treatment of acute kidney transplant rejection, and for the treatment of acute graft-versushost disease (GVHD), a potentially fatal complication that occurs when immune cells of the foreign graft initiate an inflammmatory reaction against tissues of the recipient. A multicentre, phase II clinical trial for the latter indication is evaluating the effects of BTI 322 in adult recipients, of allogenic bone marrow or stem cells, who have experienced acute GVHD and have not responded to corticosteroid treatment. BTI 322 is also undergoing development for the treatment of other autoimmune diseases.A humanised form of the product (MEDI 507), which is currently being prepared by MedImmune, is undergoing clinical trials for the prevention and treatment of acute kidney transplant rejection.BTI 322 is also a component of a new specific immune tolerance therapy which is being developed by BioTransplant for the transplantation of human organs with reduced chronic immune suppression (AlloMuneTM) and for the transplantation of porcine organs into humans (XenoMuneTM). Under the AlloMuneTMregimen, a 3-stage treatment being tested; transplant patients first receive BTI 322, then radiation treatment followed by bone marrow transplantation from the organ donor, before finally receiving the organ itself. The chimeric bone marrow created by the bone marrow transplantation educates the T cells in the thymus to accept tissue from both the host and the donor as ‘self’. MedImmune has no rights to the development or commercialisation of either AlloMuneTMor XenoMuneTMaccording to the agreement with BioTransplant.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Campath-1G (Campath IgG, Campath-1-IgG antibody) is a rat anti-human IgG2b monoclonal antibody specific for the campath-1 (CDw52) surface antigen on T lymphocytes. It effectively depletes lymphocytesin vivo. Campath-1G was isolated by researchers at Cambridge University (England) and has been assigned to British Technology Group and licensed to Glaxo Wellcome (UK). Phase II clinical trials for the treatment or prophylaxis of organ transplant rejection and graft-versus-host disorders are underway in England and South Africa.Campath-1G effectively depletes donor lymphocytes by specific specifically targeting the campath surface antigen on these cells to prevent graft-versus-host disease (GVHD). However, depletion of mature lymphocytes may result in elimination of immunocompetent cells responsible for control of infection.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

CHH 380 (chimeric anti-CD7 antibody, SDZ CHH 380) is a chimeric mouse/human monoclonal antibody which acts against the CD7 protein (a prime mediator of immunological responses) on the surface of activated T cells, thereby blocking their action. Novartis has discontinued development of CHH 380, but Celltech (UK), Genentech (USA), the Royal Free Hospital (UK) and Stanford University (USA) are developing the drug for the prevention/treatment of organ transplant rejection and rheumatoid arthritis. Development for use in transplant rejection is in phase III clinical trials in Canada, the UK and the USA. CHH 380 is available for licensing.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

The soluble tumour necrosis factor (TNF) receptor, etanercept (Enbrel®, TNFR-Fc, TNR 001), is a fusion peptide consisting of 2 molecules of the p75 TNF&agr; receptor linked to the Fc portion of immunoglobulin G1. Etanercept antagonises the activity of the immunostimulant cytokine TNF&agr;. Produced by various lymphoid cells in response to inflammatory stimuli, low concentrations of TNF&agr; increase macrophage and polymorphonuclear leucocyte cytotoxic effects, stimulate polymorphonuclear leucocyte cell surface receptors and regulate the production of other cytokines.Immunex (American Home Products) holds commercial rights to etanercept for North America and Wyeth-Ayerst (also American Home Products) has exclusive rights for territories outside North America. Boehringer Ingelheim in Germany is responsible for manufacturing the drug in commercial quantities.Etanercept has been launched in the US for the treatment of moderate-tosevere rheumatoid arthritis in patients who have had an inadequate response to disease-modifying antirheumatic drugs. Etanercept may be used in combination with methotrexate. The potential of etanercept for use in organ transplant rejection indications is being investigated in preclinical studies in Canada and in phase I/II clinical trials in the US. Immunex is also conducting a phase II clinical trial in the US of etanercept in patients with advanced congestive heart failure. Immunex and the National Institute of Infectious and Allergic Diseases in the US have completed a phase I trial of etanercept for the treatment of advanced HIV-1 infection.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;FTY 720 is a novel immunosuppressant agent derived from the ascomycete Isaria Sinclairii through modification of the structure of myriocin (ISP-I), the original product obtained from the culture filtrates of this fungus. It has a unique mechanism of action as it works by inducing lymphocytes involved in the immune response by apoptosis.It is under development with Yoshitomi and Taito in Japan, where it is in preclinical trials for possible use in autoimmune diseases, graft-versus-host disease and organ transplant rejection. The developers claim that FTY 720 requires only a low dose and has few adverse reactions.Novartis has licensed worldwide clinical development and marketing rights of the compound outside Japan for the use in transplantation and autoimmune diseases.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

Inolimomab [anti-CD25 monoclonal antibody B-B10, anti-interleukin-2 receptor monoclonal antibody B-B10, B-B10, BT 563, Leukotac®] is a murine IgG1-kappa monoclonal antibody directed against the &agr;-chain (pp55 region) of the human interleukin-2 receptor (CD25). It is undergoing clinical trials with Biotest Pharma in Germany for the suppression or reversal of graft-versus-host disorders (GVHD) and acute transplant rejection (phase III). It is also undergoing clinical trials in France (phase III) for GVHD, and clinical trials in the Netherlands (phase III) for the prophylaxis of organ transplant rejection.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

ISIS 2302 (INXC ICAM1, Oligo-TCS®) is a novel anti-inflammatory agent which acts by inhibiting the synthesis of intercellular adhesion molecule-1 (ICAM-1), a surface glycoprotein which promotes leucocyte adhesion during immune and inflammatory responses. ISIS 2302 is a human antisense phosphorothioate oligonucleotide composed of 20 bases (GCCCAAGCTGGCATCCGTCA) which targets the RNA of ICAM-1, thus inhibiting its translation from RNA to peptide. ISIS 2302 is the analogue of a murine ICAM-1 inhibitor, ISIS 3082, a research tool used to test the effects of inhibiting ICAM-1 in animal models and that has demonstrated the ability to prolong cardiac graft survival in mice.ISIS 2302 is in phase II trials for a variety of inflammatory diseases with Isis Pharmaceuticals in the USA and with Boehringer Ingelheim, a licensee company, in Europe. These studies cover 5 disease areas: renal transplant rejection prophylaxis, ulcerative colitis, Crohn's disease, psoriasis and rheumatoid arthritis. The pivotal-quality phase IIb trial of ISIS 2302 for the treatment of Crohn's disease has been initiated in 300 patients with steroid-dependency in about 40 clinical sites in North America and in Europe. An aerosol formulation of ISIS 2302 is being explored in preclinical studies as a potential therapy for asthma.Intravenous ISIS 2302 resulted in some clinical improvement in patients with psoriasis, but this effect was only short-lived. The company is now conducting preclinical investigation of topical ISIS 2302 for the treatment of psoriasis.Isis Pharmaceuticals is working with Inex Pharmaceuticals on the development of a transmembrane carrier systems (TCS) formulation of ISIS 2302, called INXC ICAM1, for intracellular delivery to endothelial cells. TCS is a proprietary delivery system developed by Inex. It aims to fully encapsulate drugs and carry them to disease sites and into cells. In preclinical studies, high levels of encapsulation into the TCS have been achieved, with a significant increase in drug accumulation at sites of inflammation. At present the TCS formulation is being investigated in the US as an anti-inflammatory agent.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

&NA;The isoxazole derivative leflunomide (HWA 486, SU 101) is a heterocyclic oral prodrug of the active compound A 771726 that has immunosuppressant and anti-inflammatory properties. Its mechanism of action is different to those of other immunosuppressant drugs (including corticosteroids, sirolimus, tacrolimus, cyclosporin and mycophenolic acid), as it inhibits tyrosine kinase and dihydroorotate dehydrogenase, thereby disrupting DNA synthesis in immune cells with consequent inhibition of immunoglobulin secretion and lymphocyte proliferation. Leflunomide's mechanism of action is yet to be fully clarified, however. Leflunomide has been launched in the US as Arava® for the treatment of rheumatoid arthritis in adults.Leflunomide is also being developed for use in organ transplant rejection indications, and has undergone phase I trials in the US and preclinical trials in Belgium, Canada, Germany and the UK. In addition, leflunomide is undergoing a multicentre phase II for the treatment of psoriasis. The compound is also undergoing preclinical trials in Germany for the treatment of multiple sclerosis, systemic lupus erythematosus, autoimmune uveitis and other autoimmune disorders. Leflunomide may have potential to attenuate a major complication of immunosuppression, cytomegalovirus infections, and has demonstrated a novel mechanism of anti-viral activity in preclinical investigations.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS

摘要:

MEDI 500 (G 022, anti-TCR-&agr;&bgr; monoclonal antibody T10B9, T10B9, T10B9.1A31, T-10B9 monoclonal antibody, T12A10) is a murine monoclonal antihuman T cell antibody which is specific for the T cell receptor (TCR)&agr;&bgr; heterodimer found on the surface of most T cells. It is believed that when MEDI 500 binds to these T cells, it suppresses their function, thereby reversing acute organ rejection which is thought to be mediated largely by T cells.MedImmune (USA) began developing MEDI 500 using exclusive rights acquired from the University of Kentucky Medical Center (USA). The drug is now being codeveloped by MedImmune and BioTransplant (USA) after the 2 companies formed a strategic alliance to develop products for the prevention and treatment of organ transplant rejection. MedImmune will fund and assume responsibility for clinical testing and commercialisation of any resulting product.In the USA, MEDI 500 is undergoing clinical development for the treatment of liver transplant rejection, acute heart transplant rejection (phase I) and acute kidney transplant rejection (phase II), and forex vivoT cell depletion for the prevention of acute graft-versus-host disease following bone marrow transplant (phase III). The University of Kentucky has completed phase II trials for the treatment of kidney transplant rejection. MEDI 500 has been used in over 500 patients under physician INDs. The primary potential benefit of MEDI 500 over muromonab CD3 (the only marketed monoclonal antibody for the reversal of acute renal rejection) is an improved adverse effects profile. However, the main apparent disadvantage of MEDI 500 is a short half-life necessitating a more frequent dosing schedule than muromonab CD3.A humanised version of MEDI 500 is under development for the treatment of autoimmune disorders and T cell cancers.

ISSN:1174-5886    

出版商:ADIS    

年代:1999

数据来源: ADIS