Oxigene Neu-Sensamide NDA may reference Sensamide pivotal data, FDA has told company -- CEO.

OXIGENE NEU-SENSAMIDE RADIATION SENSITIZER ON TRACK FOR 1998 NDA filing, Oxigene CEO Bjorn Nordenvall, PhD, indicated during a UBS Securities conference in London April 15. A Phase III trial of the high-dose metoclopramide formulation will be completed by the second quarter of 1998, putting the drug on track for a 1999 launch, Nordenvall estimated. The company plans to use a Phase III trial of an earlier formulation, Sensamide, to support the application. FDA has told the company that data from the two formulations can be included in the Neu-Sensamide NDA, Nordenvall said.

Oxigene recently completed patient enrollment in its 218-patient Phase III trial of Sensamide. The trial randomizes patients with stage III non-small cell lung cancer to Sensamide plus radiation or radiation alone. While the trial is being conducted at 15 Northern European hospitals, the study is designed to meet FDA guidelines, Nordenvall said. Results will be presented at the Ninth European Cancer Conference Sept. 13 in Hamburg.

Sensamide has been associated with Parkinson-like central nervous system side effects that can persist for up to 12 hours and must be administered intravenously because of its acidity, Nordenvall said. Neu-Sensamide may be administered intramuscularly and has significantly reduced CNS side effects, Nordenvall maintained. The patent for Neu-Sensamide extends through 2016.

The Neu-Sensamide trial, which is similar in design to the Sensamide Phase III study, will be conducted at 25 hospitals to speed recruitment. Five of the sites will be in the U.S. On April 29, the company announced a collaboration with Harvard Medical School and M.D. Anderson Cancer Center to work on Neu-Sensamide trials as well as trials of other agents. The company also announced plans to open a Boston office to oversee its U.S. clinical activities. Oxigene has offices in New York and Sweden.

To support a claim for Neu-Sensamide use as a radiation sensitizer in all cancers, FDA told Oxigene it must show efficacy in lung cancer and another unrelated cancer, Nordenvall said. The company began a 15-patient Phase I/II trial in glioblastoma patients nine months ago.

Using the NSCLC trials as a model, Oxigene will begin a pivotal trial of Neu-Sensamide in glioblastoma at U.S. and European hospitals following conclusion of the early stage study, Nordenvall said. Until Neu-Sensamide gains approval for the additional cancer indications beyond NSCLC, Nordenvall predicted that there is a "good chance" the drug would be used off-label.

Oxigene has done smaller trials in other cancers, including those of the breast, prostate, and ovary. Oxigene maintains that the high-dose metoclopramide works by blocking the DNA repair function of cancer cells when they are damaged by radiation or chemotherapy, induces apoptosis in cancer cells, and accumulates in the tumor. It also inhibits inflammation through inhibition of TNF-alpha factor, Nordenvall said. The company plans to market Neu-Sensamide in Northern Europe but will seek a partner for North America, the Far East and the rest of the world.

Oxigene will file an IND in May for the chemotherapy sensitizer Oxi-104 for refractory solid tumors, Nordenvall said. Oxigene is considering using Oxi-104 to sensitize cancer patients to cordycepin, a Boston University drug with activity against leukemia and other blood cancers, Nordenvall indicated. BU has started Phase I trials of cordycepin; Oxigene has the right to license the product after Phase I.