Immunosuppressants in advanced clinical development for organ transplantation and selected XXXX .

@entity1 @entity10479 @entity6963 @entity500 @entity1569 @entity5 @entity39 @entity3446 @entity205 @entity618 @entity1140 @entity15 @entity1499 @entity792 @entity309
Immunosuppressants dampen the immune response or restore balance among immune system components. They are primarily used to prevent allograft rejection after organ transplantation and to prevent or treat disease flares in @entity792 . Immunosuppressants available at present include the calcineurin inhibitors ( @entity205 , @entity1140 ), antimetabolites ( @entity500 , @entity6963 , @entity1499 , @entity618 ), antiproliferatives ( @entity3446 ), monoclonal antibodies to T lymphocyte (basiliximab, daclizumab, muromonab-CD3) and anticytokines (anakinra, etanercept, infliximab). The immunosuppressive market grows at a rate of > 10% yearly, with total sales in 2001 of @entity10479 2.7 billion. Immunotherapy in transplantation and @entity792 is tending towards the use of multi-drug regimens tailored for the individual @entity1 . At least 23 new immunosuppressants are currently in advanced clinical testing or preregistration, and can be divided into three groups. First, emerging drugs targeting intracellular ligands in immune cells are primarily analogues of currently-marketed agents, which attempt to provide improved pharmaceutical or safety profiles compared with the prototype compound. They are largely being developed in organ transplantation. Second, emerging drugs targeting cell surface ligands on immune cells attempt to antagonise novel molecular sites to interfere with immune cell activation via costimulatory signals, immune cell adhesion to tissues or the vasculature and immune cell trafficking. These agents are being primarily developed in @entity309 , @entity1569 and/or @entity15 . Finally, emerging drugs acting as anticytokines, which largely follow on from the success of those on the market, by antagonising the function of @entity5 @entity39 factor or a narrow selection of interleukins. All are being assessed in @entity309 . Drug development of immunosuppressants is increasingly attempting to intervene in disease progression over the long term. These efforts bring with them trial design and regulatory issues, such as what markers can be used as trial outcome measures, over what duration do trials need to be conducted and what labelling claims are allowed. With the intensive activity in this field, it is likely that several new drugs will reach the market in the coming decade. One caveat, however, is that emerging immunosuppressants that are likely to capture a reasonable share of this increasingly-fragmented market must demonstrate the ability to achieve disease remission or long-term slowing of disease progression.
