Washington Editor

Amgen Inc. is requesting U.S. regulatory approval under fast-track guidelines for palifermin, a first-in-class investigational compound for oral mucositis.

The potential indication would be to reduce the incidence, duration and severity of oral mucositis in patients with hematologic malignancies undergoing high-dose chemotherapy, with or without irradiation, followed by a bone marrow transplant. If approved, palifermin would be the first therapy for the indication, the Thousand Oaks, Calif.-based company said.

Currently marketed treatments include certain mouthwashes to address the pain associated with the illness.

Trish Hawkins, Amgen spokeswoman, told BioWorld Today the firm hasn't given guidance as to when it expects FDA action. However, fast-track products in general are reviewed in six months.

Palifermin, a recombinant human keratinocyte growth factor, targets epithelial cells lining the mouth and gastrointestinal tract by binding to certain epithelial cell-surface receptors. That binding stimulates epithelial cell proliferation, differentiation and up-regulation of cytoprotective mechanisms.

Amgen licensed the compound from the National Institutes of Health in Bethesda, Md., in 1991.

The BLA is based on a pivotal 212-patient Phase III study, which demonstrated that patients with hematologic malignancies undergoing high-dose chemotherapy, with or without irradiation, and bone marrow transplant support who received palifermin, suffered less ulcerative oral mucositis (Grades 2-4) compared to those receiving placebo (15.7 days vs. 8.4 days).

Patients were randomized to receive either palifermin (106 patients) at a dose of 60 mcg/kg per day, or placebo (also 106 patients), for three days before high-dose chemotherapy and total-body irradiation. All patients then received peripheral blood progenitor-cell transplants, followed by three more days of either palifermin or placebo.

Palifermin helped protect patients from the most severe form of oral mucositis (Grade 4) with 20 percent of palifermin-treated patients experiencing that side effect, compared to 62 percent of placebo-treated patients, Hawkins said.

On average, patients receiving palifermin reported a reduction in soreness of 54 percent, compared to the placebo arm (p=0.0001). The reduction in soreness translated into, on average, a 40 percent improvement in palifermin-treated patients' ability to eat, drink, swallow, sleep and talk (p<0.001).

Amgen presented the data last year at the American Society of Clinical Oncology meeting and at the American Society of Hematology meeting. (See BioWorld Today, June 2, 2003, and Dec. 10, 2003.)

As part of a $86.5 million deal, Biovitrum AB, of Stockholm, Sweden, has Nordic co-promotion rights to palifermin in oral chemotherapy-related inflammations. Amgen owns all other rights. (See BioWorld Today, Sept. 9, 2003.)

Amgen is pursuing regulatory approval of palifermin in other countries outside Europe.

In other business late Thursday, Amgen said data from a Phase III study demonstrated that administration of Neulasta (pegfilgrastim) in the first and subsequent cycles of chemotherapy significantly lowered the rate of infection, as manifested by febrile neutropenia (low white blood cell count with fever), hospitalization and the use of intravenous anti-infectives in breast cancer patients receiving moderately myelosuppressive (strong) chemotherapy. The results will be presented today at the Multinational Association of Supportive Care in Cancer annual meeting in Miami.

Neulasta was approved by the FDA in 2002 for decreasing the incidence of infection, as manifested by chemotherapy-induced neutropenia, in patients with nonmyeloid malignancies receiving myelosuppressive cancer drugs with a clinically significant incidence of febrile neutropenia. Similar indications for Neulasta were approved in Europe and Australia the same year.

Amgen's stock (NASDAQ:AMGN) was up 30 cents Thursday to close at $54.52.