A white powdered chemical compound emerged from two University of Maryland School of Medicine laboratories more than 10 years ago with a name destined for oblivion, but a future that now looks promising as a treatment for the most challenging cases of prostate cancer.
Today, VN/124-1 is a drug candidate with a name — galeterone — a pharmaceutical company founded on its potential and a record of strong preliminary results in clinical trials with human patients.
The Food and Drug Administration has put galeterone on a fast track for approval to treat prostate cancer, which kills about 30,000 men a year in the United States. Researchers in hospitals and clinics across the country and in Canada are finishing the trial's second round and preparing for the third, expected to begin early next year.
Dr. Kevin J. Cullen, director of the University of Maryland's Marlene and Stewart Greenebaum Cancer Center, acknowledged that results are preliminary, but he said it's an auspicious beginning.
"I can think of maybe one other drug in the 30 years I've been doing oncology that showed these kind of results," Cullen said. He called it an "incredibly promising start for this medicine."
Dr. Mario Eisenberger, heading the clinical trial at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, said the drug has had impressive results, but "I don't think anyone can say at this point in time whether galeterone is going to be better than the other" drugs already used to treat prostate cancer.
Before galeterone was a medicine, it was a compound born of a collaboration that began in 1996 between two University of Maryland researchers, Angela M. H. Brodie and Vincent C.O. Njar.
The approach was built on work for which Brodie has won some of the most prestigious awards in the field — research not in prostate but breast cancer. In the last 10 years, she won the Charles F. Kettering Prize and the Dorothy P. Landon-AACR Prize for Translational Cancer Research for her work in the 1970s and 1980s helping to develop compounds that block production of estrogen, the female hormone, that fuels the growth of most breast cancers.
More recently, she's turned her attention to prostate cancer, which feeds on the male hormone. She wondered if the approach that worked with estrogen would work with the androgens, or hormones, that fuel prostate cancer: testosterone and the more potent dihydrotestosterone.
Up to now, one main treatment for the most challenging prostate cancers has been shutting down androgen production from the testicles. The procedure, referred to as castration, is most commonly done today by medication not surgery. The testicles produce about 90 percent of the body's androgen. Most of the rest is produced by the adrenal glands, and a small measure from the prostate tumor itself.
Njar and Brodie were looking for a way to fight prostate cancer that continutes after castration.
Their approach is one in a succession of hormone-based treatments that have been used for years, but it's different in combining several effects at once. This one works in three ways to interfere with androgen's effect on prostate cells.
The medication decreases androgen production and interferes with the process by which the substance binds to the prostate cell molecule that responds to the hormone, known as the receptor. These effects have been produced before, but galeterone is the only medication that also appears to damage the receptor itself.
The triple threat showed impressive results in tests with mice about 10 years ago. Brodie and Njar and their research team published results in the Journal of Medicinal Chemistry in 2005, concluding that the compound "is a potent inhibitor of human prostate tumor growth and is remarkably more effective than castration."
After that publication, Tokai Pharmaceuticals, a company in Cambridge, Massachusetts, named and licensed the compound as "galeterone." Clinical trials with human patients started in November 2009.
To fund its anticipated growth, Tokai applied in August to sell $75 million of stock in an initial public offering. While its stock sale is pending, company officials are not available for comment.
According to information posted on Tokai's website, researchers have given the drug to 200 patients in the first two trial phases.
Of the 49 patients in the first trial, 24 showed 30-percent reduction in prostate specific antigen, or PSA, and 11 showed a 50-percent cut. Elevated levels of PSA can be, but are not necessarily, a marker for prostate cancer.
In the second phase, 51 patients — both with and without metastasis, or cancer spread beyond the prostate — followed for 12 weeks also showed significant PSA reductions. Of this group, 82 percent to 85 percent experienced reductions of about a third, three-quarters saw a reduction by at least half.
Cullen said he was struck by the results even in the first phase, conducted less for effects on the cancer than to see how well patients can tolerate the medication at low doses. With such low doses in the first phase of a clinical trial, results like that are "almost unprecedented," he said.
Galeterone causes none of the adverse effects associated with chemotherapy, including nausea and hair loss. So far, Brodie said, the chief side effect could be deficiency of cortisol, but that has not been a problem so far. The hormone plays a role in regulating blood sugar, suppressing immune response and metabolizing fat, protein and carbohydrates.
Eisenberger said the effects can include fatigue and itching, but nothing requiring cortisol treatment.
Brodie and Njar are making no bold pronouncements at this point, just eagerly awaiting further results.