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NOVEL ANTI-TUMOR DRUG TAKES
IMPORTANT STEP TOWARDS FDA APPROVAL

A novel anti-cancer compound synthesized by scientists at the University of California, San Diego more than a decade ago from toxins of the poisonous jack-o-lantern mushroom, has been granted “fast track” status by the U.S. Food and Drug Administration (FDA) after demonstrating promise against one of the most deadly cancers.

“Fast track” designation, an important accelerated phase in the nation’s drug review and approval process, signifies that the FDA can expedite the review and development of the drug candidate irofulven, which in clinical studies has demonstrated shrinkage of solid tumors of the pancreas and other cancers.  Pancreatic cancer claims an estimated 29,000 lives each year in the United States and about 170,000 lives worldwide.  It is one of the most deadly malignancies and has few effective treatment options.

Irofulven is currently being developed by MGI PHARMA, Inc., an emerging oncology-focused pharmaceutical company based in Minneapolis. Phase III clinical trials involving the drug have been underway since early this year at sites in the U.S. and Europe.   
            

“It’s very exciting and rewarding to see the drug reach another important milestone as it moves toward possible approval by the FDA,” says Trevor McMorris, UCSD professor of chemistry, who, with Michael Kelner, professor of pathology in the UCSD School of Medicine, led the original biochemical and biomedical research studies involving the drug.  In 1989, McMorris and Kelner first demonstrated the anti-tumor activity of acylfulvenes, the chemical compound family from which irofulven is derived. (Acylfulvenes, in turn, originate from illudin-S, a toxic constituent of the jack-o- lantern mushroom.)

McMorris and Kelner later began testing and comparing the metabolism of acyfulvenes with that of illudin-S in animal studies, gaining further insight into the compound’s anti-tumor activity.

The two scientists, both members of the UCSD Cancer Center, are continuing to explore and test other acylfulvene-based cancer drug analogs. “We’ve followed the progress of this drug with great interest,” says Kelner, “especially as it advanced from phase I and II of clinical trials conducted by MGI PHARMA and the National Cancer Institute.  Now that irofulven is a phase III clinical trial and has received a ‘fast track’ designation, it’s rewarding to realize this drug could be in its final stage toward receiving FDA approval and may become available to help thousands of cancer patients.”

Irovulven appears promising in pancreatic cancer patients who are no longer responding to gemcitabine, the conventional drug treatment for this disease. In addition, the compound has also demonstrated activity against ovarian cancer (particularly with patients who have had limited or no success with such standard cancer drugs as cisplatinum and paclitaxel) and prostate cancer.

In 1993, MGI PHARMA acquired the rights from the University of California to all illudin-S analogs devised by McMorris and Kelner, including irofulven, which was first synthesized by McMorris.

Irofulven’s unique mechanism of action as an anti-tumor agent is due to its ability to be rapidly absorbed by tumor cells.  Once inside the cells, the compound binds to DNA and protein targets.  This binding interferes with DNA replication and cell division of tumor cells, leading to tumor-specific apoptotic cell death, or “cell suicide.”  During this process, tumor cells tend to automatically shut themselves down when they sense their function is compromised.

Side effects from irofulven are comparable to marketed chemotherapies and include bone marrow suppression (decreased platelets or white blood cell counts), nausea, vomiting and fatigue.

Patients and health care providers seeking information on the various irofulven clinical trials may call MGI PHARMA’s Medical Communications Help Line at
1-800-562- 5580, or the National Cancer Institute’s Cancer Information Service at 1-800-4-CANCER (TTY 1-800-332-8615).