30,000 suffering in Tucson, Phoenix areas
Dr. Susan Hoover, Dr. John Galgiani (center) and Dr. David Nix are preparing to begin an FDA human clinical trial to prove the safety and effectiveness of a drug they hope will cure valley fever.
University of Arizona researchers are ready to launch a long-delayed human clinical trial on a drug they hope will cure valley fever.
Nikkomycin Z, discovered in the 1970s, will be tested in Tucson on people diagnosed with fresh cases of valley fever to show the drug’s safety and offer insights on its effectiveness, said Dr. John Galgiani, director of the Valley Fever Center for Excellence.
Valley fever – also known as Coccidioidomycosis – is a fungal pneumonia with no cure that primarily strikes people in desert areas of southern Arizona and the San Joaquin Valley in California, Galgiani said.
Microscopic valley fever spores, 3 to 5 microns in size, are found in soil. Disruption from construction or wind helps the spores go airborne where they can be inhaled into the lungs, he said. The spores then change into larger structures, spherules. The spherules grow and burst, releasing endospores. Each endospore can turn into a new spherule and increase the infection.
Valley fever, which is not contagious, usually results in fever symptoms within three weeks of exposure. People who live in the area long enough are likely to contract the disease, Galgiani said, even though they may attribute the illness to a cold or the flu.
Arizonans living in Tucson and Phoenix and along the Interstate 10 corridor account for 100,000, or 60 percent, of the valley fever infections seen each year, Galgiani said.
Of that number, about 30,000 are sick enough to seek medical attention, he said.
Some people recover on their own without medical intervention, Galgiani said.
A moderate, uncomplicated case runs from weeks to months and includes a cough, chest pain, fever, weight loss, fatigue, bone and joint pains and skin rashes.
In some cases, people die.
Tucsonan John Piikkila, 62, has suffered valley fever’s effects on and off since 1976. He believes he contracted the disease while building his home.
He has been hit with fevers, weakness, fungal outbreaks and joint pain for decades.
The availability of nikkomycin Z could have changed his life, he said.
“That would have been a world of difference. I could have avoided double pneumonia and a lot of things,” Piikkila said. “It cost me a lot of time, sapped my strength and it was pretty drastic.”
Lab mice were successfully cured of valley fever in the 1980s, and researchers hope the clinical trial will show that nikkomycin Z will kill the fungus in humans.
Existing treatments suppress but do not eradicate the disease, Galgiani said.
The research group, headed by Dr. David Nix, Dr. Susan Hoover and Galgiani, received $1 million from the U.S. Food and Drug Administration in August to fund the clinical trial, slated to last three years.
The three researchers are UA professors and members of the BIO5 Institute, which seeks to tackle scientific problems through ramped-up collaboration among scientific disciplines.
Researchers are ready to begin enrolling qualified participants, who must meet specific criteria and will be referred to the study by their physicians, said Hoover, medical director of the clinical trial.
In Tucson, valley fever has been the leading single cause of death in people with AIDS, Galgiani said.
The primary focus of the clinical trial is proving the safety of the drug, Hoover said. Participants will have their vital signs and liver and kidney functions checked during and after their participation.
The effectiveness of the drug will be checked by monitoring how participants feel and how chest X-rays and CT scans show the pneumonia before and after administration of the drug, Hoover said.
The clinical trial will not determine what dosage is needed to cure valley fever. That will take place in a Phase 3 trial following the current phases 1 and 2 human trials, pending funding, she said.
The current trial will start patients on a dose of 50 milligrams twice a day, said Nix, principal investigator for the clinical trial.
After that dose is shown safe, the dosage will be increased on subsequent participants until it reaches 750 milligrams three times daily, he said.
Nikkomycin Z was discovered by Bayer AG in the 1970s while the company sought ways to suppress the growth of fungi in produce to avoid food spoilage.
Medical applications were discovered in 1990, and California-based Shaman Pharmaceuticals, a natural products company, obtained the drug in 1995.
The company in 1997 ran a 12-person, single-dose Phase 1 trial in England to investigate safety. No problems arose in that phase, which studies the safety of a drug in healthy subjects.
The drug was purchased in 2001 by California State University’s Bakersfield Foundation for Research.
UA, eager to try to move the drug to the market, purchased nikkomycin Z in May 2005, and the Valley Fever Center for Excellence began efforts to raise funds to get clinical trials moving.
Finally, after 10 years of no activity, a clinical trial needed to bring the drug to market is funded and ready to go.
The UA team has 2.5 kilograms, or 5.5 pounds, of nikkomycin Z remaining for tests, project leader Galgiani said.
That amount has been put into capsules and should be enough to meet the needs of the current clinical trial.
It will cost more than $2 million to produce more of the drug to be used in a Phase 3 trial required before it can be approved for use, Galgiani said.
The National Institutes of Health donated $400,000 worth of lab work that verified the remaining drug was suitable for testing, he said.
The institutes also donated $225,000 to fund planning for the initial trial, Galgiani said.
“It’s a priority project with NIH,” Galgiani said. “Valley fever is an unmet need. No drug cures the disease.”
Lack of funding caused the decadelong delay in testing the drug.
Nikkomycin Z was designated by the FDA as an orphan drug because it fights a disease that has fewer than 200,000 victims at any one time, Galgiani said.
At any given time, 50,000 people have valley fever, of which 30,000 are in Phoenix, Tucson and within 50 miles of the I-10 corridor between the cities, he said.
“It doesn’t seem like an orphan disease here because it is so prevalent,” he said.
It would cost $40 million to $60 million for additional testing and the manufacturing needed to bring the drug to a pharmacist near you, and investors must be attracted to commercialize the drug, Galgiani said.
A successful trial could prove the value of nikkomycin Z to investors, Hoover said.
Even though the clinical trial is ready to begin, weather will play a role in the study.
The peak incidence of valley fever is October to December, after the soil dries out and the spores become airborne following the summer monsoon rains, when the number of infections falls, Galgiani said.
Another spike in infections runs from April to July, he said.
Finding suitable infected participants may take some time, he said.
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Valley fever spores such as these are actually 3 to 5 microns in size. After being inhaled, they reproduce and cause infection.
John Piikkila, who was diagnosed with valley fever in 1976, believes he contracted the disease while building his home in the Tucson area.
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If you want to participate in the study
People selected for the nikkomycin Z clinical trial must be referred to the program by their physicians.
Subjects may be ages 18 to 50, male or female. Those who are pregnant are not eligible.
Eligible subjects must have experienced symptoms for less than 30 days and must be enrolled in the study within seven days of diagnosis.
Participants will begin with a baseline health study followed by two weeks of drug administration and two weeks of follow-up.
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ON THE WEB
Valley Fever Center for Excellence: www.vfce.arizona.edu
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