from today's Contra Costa Times:
Firm makes big bet on novel cancer drug
SuperGen hopes decitabine will pay off as treatment, but it still needs FDA approval
By Judy Silber
CONTRA COSTA TIMES
--------------------------------------------------------------------------------
The future of a novel cancer therapy was in doubt when Dublin-based SuperGen Inc. decided to invest in it.
Called decitabine, the drug had languished in clinical trials for more than 15 years. The Israeli company that had acquired it through a merger didn't want it.
But executives at SuperGen saw potential in decitabine. It attacked cancer through a biochemical mechanism increasingly recognized by researchers as important. Recent clinical trials had started a buzz among physicians that a new application of the therapy had promise.
Trading stock for the drug, SuperGen acquired decitabine in September 1999.
While the drug's future is still uncertain, recent studies have generated hope that SuperGen's bet on decitabine will pay off. Buoyed by positive results from a recent clinical trial, the company is now considering applying for European approval of the drug.
There's no guarantee decitabine will prove an important addition to the arsenal of cancer-fighting therapies. None of the clinical trials currently testing the drug's effectiveness have been completed, leaving approval from the U.S. Food and Drug Administration --necessary to sell the drug -- uncertain.
But enthusiasm has accelerated. The number of scientific publications about decitabine more than doubled in 2000 compared with 1999. SuperGen has helped carry out nearly a dozen clinical trials for a variety of cancers. And a Scottish research group will soon begin yet another, focusing on whether decitabine can help patients whose exposure to chemotherapy has made them resistant to treatment.
"We're all so excited about how things are happening so quickly now," said Dr. Karl Mettinger, SuperGen's chief medical officer. "This is really becoming a hot area in cancer research."
SuperGen could use a success story.
Over the past year, the company has lost favor with Wall Street as investors scorned all but the most successful biopharmaceutical companies, said Gary Davis, senior vice president of equities research at Jesup & Lamont. Collecting data about what many consider SuperGen's most promising product -- rubitecan, for pancreatic cancer -- has taken longer than expected. Additionally, in December 2000, several key executives left the company, said Davis.
The company's stock has suffered. It closed at $11.97 on Monday, far below its 52-week high of $30.75.
Unlike many biopharmaceutical companies, SuperGen doesn't develop drugs from scratch. Rather, since 1991, it has licensed or bought drugs from other companies and shepherded them through clinical trials. Only one has gotten FDA approval, a therapy called Nipent for hairy cell leukemia. And while that's one more than many small biopharmaceutical companies, Nipent's approximately $10 million in sales aren't enough to support SuperGen's research activities, let alone post a profit.
Positive results from either decitabine or rubitecan could give the company a substantial boost, for both have potentially large markets. Much of the research on decitabine focuses on blood disorders like leukemia, but the company has also begun testing decitabine in combination with other chemotherapy drugs on solid tumors like breast, colon and lung cancer.
So far, the studies are only preliminary. However, results from a phase II clinical trial on myelodysplastic syndrome, a pre-leukemic syndrome primarily afflicting the elderly, are so compelling the company is considering applying for European approval. A phase III trial, most likely necessary for FDA approval, is expected to take another 18 months. While only about 10,000 U.S. patients a year may benefit, FDA approval would at least put decitabine on the market. Since oncologists often use approved drugs to treat other diseases, demand for the drug could then broaden.
But perhaps the most exciting possibility for decitabine is that of reversing the resistance many cancer patients develop to chemotherapy. Resistance prevents the anti-cancer drugs from working, accelerating the progress of the disease. If encouraging results from animal studies hold up in people, decitabine could have widespread use for many cancers.
Decitabine's relatively newfound utility stems from the discovery that it does a good job at blocking a biochemical process called methylation.
For years, researchers believed that cancer arises from successive mutations knocking out genes important in controlling cell growth. While mutations no doubt play a decisive role, over the past few years scientists have come to accept that methylation too has an impact on cancer, said Dr. Jean-Pierre Issa, an associate professor of medicine in the department of leukemia at MD Anderson Cancer Center in Houston.
Like mutations, methylation -- which adds an extra chemical group onto DNA -- disrupts the production of some proteins important for regulating cells. So far, research has shown that low doses of a drug like decitabine seemingly reverse the damage caused by methylation. Cells regain their normal complement of proteins, or at least those affected by methylation.
For some blood diseases like leukemia, that may be enough to stop cancer cells from dividing. And if decitabine can reverse the methylation implicated in chemotherapy resistance, it could mean longer lives for some cancer victims.
Of course, researchers will need to collect much more data before determining decitabine's effectiveness. However, the drug and a greater understanding of methylation have opened up new possibilities for treating cancer.
"I am excited and genuinely so," said Robert Brown, a professor of cancer therapeutics at the University of Glasgow in Scotland, who is leading the chemotherapy resistance studies. "We really are looking at a different way of thinking about drug resistance." |
