Prograf® (tacrolimus)     On March 25, 1984, a substance was discovered in a soil sample taken at the foot of Mt. Tsukuba which stands just outside Tokyo. The substance, given the name tacrolimus, was found to possess a powerful suppressive effect on interleukin-2 production.

Based on evidence that tacrolimus was able to block initial T-cell activation, inhibiting the differentiation and proliferation of cytotoxic T-cells, speculation about the substance's immunosuppressive properties grew.

Two year's later, preliminary results of studies using tacrolimus in animals were reported and the 11th World Congress of the Transplantation Society in Helsinki, Finland, by researchers from Chiba University of Japan.
 

Pivotal research in Pittsburgh

The Helsinki presentation caught the attention of transplant professionals from around the world. Almost immediately, pivotal research into the clinical safety and efficacy of tacrolimus began at the University of Pittsburgh Medical School. Meanwhile, a wide range of studies were being conducted under the direction of Fujisawa. From pharmacokinetics, to short-and long-term toxicity, tacrolimus was scrutinized relentlessly. Results of this work were presented in June 1987 at a satellite symposium of the European Society for Organ Transplantation in Gothenburg, Sweden. This early success vaulted tacrolimus into the international spotlight. The promise of what tacrolimus could offer patients was now becoming a reality.

From rescue to primary therapy

Less than five years after its discovery, the University of Pittsburgh Transplant Group began the world's first trial of tacrolimus in humans. Initially, tacrolimus was given to patients who were taking conventional drugs, but who were facing retransplantation because of ongoing rejection or undesirable toxicities. The patient and graft survival rates among these "rescue and conversion" patients were dramatic. Building on these promising results in "rescue" patients, tacrolimus use expanded quickly in the spring of 1990 to first line prophylaxis of rejection in liver patients.

Introduced to the world

Based on the data obtained from Pittsburgh, Kyoto, and other universities around the world, tacrolimus, now known as Prograf® (tacrolimus capsules and injection), received clearance from the Ministry of Health and Welfare in April 1993 and was introduced to the Japanese market in June 1993.

Based on two large Phase III comparative clinical trials, ^1,2 Prograf received clearance from the Food and Drug Administration of the United States in April 1994, and was made available in June 1994 for commercial use.

Two months later, in the United Kingdom, Prograf received clearance from the Medicines Control Agency for primary immunosuppression in kidney and liver allograft recipients, and in kidney and liver allograft rejection resistant to conventional immunosuppressive regiments.

Today, Prograf is allowing transplant professionals in multiple countries around the world to follow a new path in immunosuppression