There's no doubt about it: Medical school is demanding.
The Office of Orphan Product Development in the Food and Drug Administration has awarded $1,049,978 to The University of Arizona’s Valley Fever Center for Excellence to fund a phase 1 and 2 clinical trial for nikkomycin Z, a promising investigational treatment for valley fever.
Additional support for the development of nikkomycin Z has come from the National Institutes of Health, the Critical Path Institute, the UA’s BIO5 Institute, New York-based JT Tai & Company Foundation and donations from individuals, especially animal lovers because valley fever also is a major problem for dogs and other pets. Valley fever is a disease of the lungs caused by the fungus coccidioidomycosis that is common in the southwestern United States and northwestern Mexico.
The three-year trial is a safety trial that will involve 60 patients with primary valley fever pneumonia who have not been sick for more than 30 days prior to enrollment in the trial, says David Nix, an associate professor in the UA College of Pharmacy and BIO5 member. His responsibilities for the clinical trial include drug handling, some of the laboratory analyses, data management, safety reporting and data analysis. BIO5 member Susan Hoover, UA College of Medicine assistant professor, is responsible for evaluating and treating patients enrolled in the study. The team is ready to enroll patients, who will be referred by the physicians who diagnose them with valley fever.
Getting nikkomycin Z to this point has required a coordinated effort on the part of numerous UA departments. For example, Vahe Bandarian, PhD, an associate professor in the UA biochemistry and molecular biophysics department, is working with the bacteria that produces nikkomycin Z. Right now, the bacteria produces not only nikkomycin Z, but a range of other similar molecules that are difficult to separate from nikkomycin Z. If he is successful, the bacteria will not produce the molecule that is most difficult to separate from nikkomycin Z, thus making it easier to purify the drug. That means it will be more cost effective to manufacture the drug in large quantities.
The possibility of producing the drug by chemical synthesis is being explored by BIO5 member Robin Polt, a professor in the UA department of chemistry.
“At least nine UA departments and six sources of funding are involved thus far in moving nikkomycin Z forward,” says John Galgiani, a BIO5 member and director of the Valley Fever Center for Excellence in the UA College of Medicine and Southern Arizona VA Healthcare System. “But getting nikkomycin Z into the hands of patients with valley fever will likely require $40-60 million more than has been raised to date.”
The first clinical trial is just the beginning of a much longer process that includes running additional clinical trials, developing a less expensive process for producing the drug, simplifying the purification process and scaling up the manufacturing of the drug to make large quantities.
The 1983 Orphan Drug Act allows the federal government to assist in the development of treatments for rare (orphan) diseases, which according to the FDA, are diseases that affect fewer than 200,000 people a year. Though rare in the rest of the nation, valley fever is a serious health problem in the Southwest. There are approximately 150,000 new infections each year, 100,000 of which are in Arizona.
Valley fever is an infection caused by inhaling fungal spores found in desert soil. Most individuals contract a lung infection that is self-limiting without treatment. Symptoms range from very mild to pronounced enough to interfere with daily activities for weeks to months. A small percentage of cases are serious and often involve body sites other than lungs.
With currently available treatments, some patients require many years of treatment or even life-long therapy just to suppress the infection. In 2006, 5,494 cases of valley fever were reported in Arizona, a 45 percent increase from the 3,772 cases in 2005. The number of reported cases is a fraction of total cases, since most are not recognized.
Results from experimental studies in animal models show that the valley fever fungus can be eradicated with the drug nikkomycin Z. “This offers hope that nikkomycin Z might be curative in people,” says Dr. Galgiani. “The anti-fungal drugs now used help the immune system control the disease, but do not kill the fungus.”
Since the UA acquired nikkomycin Z in 2005, the Valley Fever Center for Excellence, the UA Colleges of Medicine and Pharmacy, the BIO5 Institute and The Critical Path Institute have been working collectively to help find appropriate mechanisms to get the drug into clinical trials and tested for efficacy in humans.
The Valley Fever Center for Excellence (VFCE) is jointly sponsored by The University of Arizona and the Southern Arizona VA Healthcare System (SAVAHCS). One of eight centers of excellence in the UA College of Medicine, the VFCE provides information to the public, physician consultations with VFCE doctors and physician referrals for patients, and promotes research into all aspects of the disease.