Immunosuppressants in Transplant Therapy

Cyclosporine is the leading immunosuppressive drug used to prevent organ and graft rejection in transplantation. Industry participants estimate that the population of transplant survivors is over 220,000 worldwide with at least 140,000 in the U.S. and at least 80,000 in the rest of the world. The majority of these patients are prescribed cyclosporine for the rest of their lives. The worldwide sales of cyclosporine products are approximately $1.2 billion with $400 million to $500 million in the U.S.

The 24,076 organ transplants performed in the U.S. in 2001 were carried out at 416 transplant centers involving 875 organ specific transplant programs. The most common organ transplant was of the kidney with over 14,000 recipients. The national transplant waiting list in the U.S. comprises 79,000 prospective patients with almost 51,000 requiring kidneys. The number of registered donors is growing and the long-term survival rate of transplant patients is improving. These factors should result in growth of the population of transplant patients requiring lifelong immunosuppression and therefore an increase in the immunosuppressant market.

The characteristics of the cyclosporine market are well matched to the implementation of booster therapy. Ample literature precedent, including long-term prospective clinical trials, of the benefits of CYP 3A inhibition in cyclosporine therapy exists. The drugs studied have included azole antifungals, calcium channel blockers and macrolide antibiotics. The most studied of these is the antifungal agent ketoconazole. Studies of various regimens with ketoconazole-boosted cyclosporine demonstrated that dosage could be reduced by 70% to 85% while maintaining therapeutic blood concentrations. No adverse drug events were reported for the co-administration therapy. A five-year follow-up study comparing patients on ketoconazole co-administration with cyclosporine versus those without boosting demonstrated that there was no clinically significant difference in patient or graft survival. Despite the apparent success of this therapy, the use of ketoconazole has fallen out of favor due to regulatory and medical misgivings regarding the prescription of drugs that have antimicrobial activity to patients that do not have relevant infections.

The systems and practices of titrating the concentration of cyclosporine in patients are already in place and can be used to monitor conversion of patients to booster-based therapy. Kidney transplant patients represent the largest population of transplant patients and will be the initial focus of a BAS Booster regulatory application. The combination of the BAS Booster and cyclosporine is projected to afford a significant pharmacoeconomic benefit.


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