New iron-chelating drugs for the treatment of transfusional iron overload and other diseases

Iron chelation therapy has improved dramatically with the introduction of deferiprone (L1) more than 10 years ago. In particular, selective deferiprone/deferoxamine combination therapy protocols appear to be universally effective in the treatment of iron overload. New chelators have also been developed, some of which are under clinical evaluation, such as deferasirox (ICL-670; Exjade), deferitrin (GT-56-252), L1NAII and starch deferoxamine polymers. ICL-670 has recently been approved by the U.S. FDA under the accelerated approval regulations with postmarketing surveillance requirements for up to 2012. It is effective in reducing liver iron but is generally ineffective in causing negative iron balance or reducing cardiac iron. ICL-670 and the other experimental iron chelating drugs have no major advantages in efficacy and toxicity in comparison to deferiprone, deferoxamine or their combination. It is likely that the new experimental iron chelating drugs will be used in combination therapies with deferiprone, deferoxamine and possibly other chelators for improving existing therapies. A major setback of these new drugs is that their cost will be prohibitive for the vast majority of thalassaemia patients living in developing countries. In contrast, the price of deferiprone is likely to be reduced because one of its major patents is due to expire.