New Growth Factor Products Highlighted at ASH Meeting

ASH—Researchers at the American Society of Hematology meeting in San Diego presented studies of three new growth factors under development by Amgen: megakaryocyte growth and development factor (MGDF); novel erythropoiesis stimulating protein (NESP); and keratinocyte growth factor (KGF).

MGDF is a recombinant segment of the Mpl ligand (thought to be the primary regulator of platelet development and proliferation) linked to polyethylene glycol (PEG).

In a phase I/II randomized, placebo-controlled study, subcutaneous administration of MGDF was shown to increase circulating platelets and total platelet yields in platelet donors and was well tolerated. Lead investigator David Kuter, MD, DPhil, of Massachusetts General Hospital, said that by improving platelet-donation efficiency, use of MGDF could reduce the recipient’s exposure to multiple donors, thus improving safety.

In this study, MGDF was given to 65 healthy platelet donors, and the resulting apheresis products were later transfused into cancer patients with chemotherapy-induced thrombocytopenia. The donors showed a significant improvement in apheresis yield, and when this product was transfused into recipients, there was a dose-dependent rise in the post-transfusion platelet count.

Roy Beveridge, MD, of Fairfax Hospital, Virginia, presented the second MGDF study, a phase II randomized, placebo-controlled trial of 50 breast cancer patients undergoing high-dose chemotherapy/ABMT with G-CSF (Neupogen).

Those receiving MGDF after transplant at one of two MGDF doses had a 34% reduction in the duration of severe thrombocytopenia and a 48% reduction in the number of platelet transfusions. The drug was well tolerated at both doses, Dr. Beveridge said, and a phase III trial is ongoing in this setting.

A similar study from UCLA in breast cancer patients showed that giving MGDF before rather than after high-dose chemo-therapy with stem cell support improved platelet counts but did not impact platelet recovery or transfusion requirements.

Longer Serum Half-Life

Preclinical studies of Amgen’s novel erythropoiesis stimulating protein (NESP) suggest that it may have clinical advantages over the company’s recombinant erythropoietin (rHuEPO, Epogen). NESP has approximately a threefold longer serum half-life than Epogen, which might permit less frequent dosing, Amgen investigator Joan Egrie, PhD, said in her poster presentation.

“NESP is both biochemically distinct from rHuEPO and has significantly increased in vivo biological activity,” she said. The agent was 3.6 times as potent as rHuEPO in increasing the hematocrit in normal mice when injected by an intraperitoneal or intravenous route thrice weekly. On a once weekly dosing schedule, NESP was about 20-fold more efficacious than rHuEPO, she said. Phase I/II clinical trials of NESP are currently being conducted in the treatment of anemia in patients with chronic renal failure.

Preventing Mucositis

In animal studies, recombinant keratinocyte growth factor (KGF) has been shown to selectively stimulate the growth of epithelial cells in the mouth, esophagus, and intestine, and may be beneficial in helping reduce severe oral mucositis in cancer patients receiving aggressive chemotherapy and/or radiation therapy. As more cancer patients receive aggressive therapy, mucositis has become increasingly common and is often the dose-limiting factor.

In a randomized, placebo-controlled phase I study, conducted in 61 normal volunteers, KGF proved safe and well tolerated at doses that elicited biological activity in the oral mucosa, Amgen researchers said at a poster presentation.

Phase I/II clinical trials are currently underway to explore the use of KGF as a treatment for the reduction of mucositis resulting from chemotherapy and/or radiation therapy in patients with head and neck cancer or advanced colorectal cancer, and in those receiving high-dose chemotherapy with stem cell support for lymphoma.