Curr Opin Investig Drugs 2001 Feb;2(2):222-30
University of Michigan Medical Center, Division of Rheumatology, Ann Arbor 48109-1065, USA.
Hoechst Marion Roussel (HMR; now Aventis Pharma) launched leflunomide (HWA-486), an immunomodulator and a disease-modifying antirheumatic drug (DMARD), for the treatment of rheumatoid arthritis (RA) in the US in late 1998 .
By August 2000, the compound had been launched extensively across all of Latin America and in all major European countries .
The compound is also under preclinical investigationfor the prevention of transplant rejection , .
In 1998, HMR filed for approvalfor RA in Europe . In September 1998, the FDA approved leflunomide for the treatment of active RA in adults and it was launched shortly thereafter , , .
In September 1999, the EU Commission accepted the view of the Committee for Proprietary Medicinal Products, published in May 1999 , , and gave approval for the use of leflunomide in RA in adults .
Lehman Brothers has reported that EU launch was delayed by rare side effects including pancytopenia .
In August 1998, the Arthritis Advisory Committee unanimously recommended that leflunomide be contraindicatedfor pregnancy, and that a pregnancy registry should be established to monitor possible teratogenic effects of the drug .
Kyorin had a licence to develop leflunomide in Japan.
Product approval was scheduled for 1998 , but no development has been reported since 1994.
Preclinical studies in an animal model of experimental allergic encephalomyelitis (EAE) have shown leflunomide to be a powerful immunosuppressant which may have potential in diseases such as multiple sclerosis .
Leflunomide is rapidly processed in vivo to its active metabolite, A-771726 (RS-61980) , .
In 1996, leflunomide was designated as one of HMR's nine top-priority products, serving an unmet medical need and addressing a potential market in excess of US $500 million per year .