Human Genome Sciences, Inc. (HGSI), a company with the mission to treat and cure disease by bringing new gene-based drugs to patients, has initiated to develop a long-acting form of Granulocyte Colony Stimulating Factor (G-CSF) for the treatment of chemotherapy-induced neutropenia. The new drug, called Albugranin, was made using Human Genome Sciences' proprietary albumin fusion technology. The Company also announced that it is discontinuing development of Mirostipen as a single, stand-alone agent for treatment of the same disorder.

Albugranin is a long-acting form of G-CSF, made by fusion of the gene for human albumin to that of human G-CSF. The fusion protein is produced in yeast cells. Albugranin stimulates neutrophil production in mice and in monkeys, and has a substantially longer half-life in the serum of both species than does G-CSF itself.

David C. Stump, M.D., senior vice president, drug development, said, "Chemotherapy-induced neutropenia is a serious medical condition requiring both close monitoring and treatment. Our preclinical studies in both mice and primates show that a single dose of Albugranin displays a long half-life, which leads to long-term stimulation and production of circulating neutrophils. Based on these pharmacologic properties, I believe it may be possible to administer Albugranin only once per each cycle of chemotherapy. Our preclinical development studies of Albugranin have progressed well. We hope to file an Investigational New Drug application with the U.S. Food and Drug Administration for treatment of chemotherapy-induced neutropenia with Albugranin within the next several weeks."

Separately, two phase 2A trials of another drug, Mirostipen, evaluated for the treatment of chemotherapy-induced neutropenia have been completed. Full details of the trials may be reported later by the clinical investigators.

The mechanism of action of Mirostipen differs significantly from that of G-CSF. Mirostipen selectively and reversibly inhibits proliferation of bone marrow hematopoietic stem cells, whereas G-CSF specifically stimulates neutrophil proliferation and release into the bloodstream. Preclinical studies demonstrated that Mirostipen spares hematopoietic stem cells from killing by cancer chemotherapy drugs and radiation.

The ability of Mirostipen to treat chemotherapy-induced neutropenia was evaluated in two phase 2A dose escalation studies. In one study, patients with primarily breast cancer were treated with doxorubicin and docetaxol. In a second study, patients with a variety of solid tumors were treated with topotecan. The patients in both studies were given daily injections of either placebo or Mirostipen just prior to and with chemotherapy through four complete cycles of treatment. Patients in the topotecan trial were also treated with G-CSF in addition to Mirostipen in cycles three and four of chemotherapy.

The results show that Mirostipen is well tolerated when administered intravenously at doses from 1ug/kg to 100ug/kg per day. Adverse events occurred similarly in patients treated with Mirostipen versus placebo. There was some evidence of Mirostipen biological activity observed in later chemotherapy cycles at the intermediate dose level, 10ug/kg/day, in one of the trials. The frequency of serious neutropenia, and the time to nadir of neutrophil counts both were decreased. In the other trial, the number of neutrophils increased earlier upon treatment with Mirostipen at 5ug/kg/day in combination with G-CSF as compared to G-CSF alone.

David C. Stump, M.D., said, "These phase 2A trials of Mirostipen show that the drug is well tolerated in patients undergoing chemotherapy. However, in my opinion, the biological activity observed in patients is not sufficiently robust to meet our criteria for continued development of Mirostipen as a single, stand-alone agent for chemotherapy-induced neutropenia. While we are discontinuing development of Mirostipen, we are accelerating our efforts to develop Albugranin for the same indication. We retain our interest in this important area of cancer supportive care and are pleased to have another promising drug to evaluate."

Craig A. Rosen, Ph.D., executive vice president, research and development, said, "Our studies with Albugranin have convinced us that the drug has the potential to provide patients with an improved treatment option for chemotherapy-induced neutropenia. Cancer supportive care is an area of great interest to our company, and an increasingly important area of medicine. I agree with our decisions to discontinue development of Mirostipen as a single, stand-alone agent, and to accelerate the development of Albugranin. Given the distinct mechanisms of action of the two drugs, the possibility remains that at some later date, Mirostipen may be developed as part of combination therapy with Albugranin."