Duncan Hunter chokes up a little when it is suggested that work he began at Western three decades ago will now, finally, be applied to saving hundreds of lives. "It's a good thing," said the Chemistry professor emeritus after a long pause. "It took 30 years and had its ups and downs. So, yes, it's emotional"
Last week, the U.S. Food and Drug Administration (FDA) approved the use of Azedra, a new compound developed by Progenics Pharmaceuticals Inc., for patients with rare tumors of the adrenal glands. Hunter developed the compound with his Western lab team and applied for the patent 30 years ago.
Azedra is "a bit like a magic bullet" for rare adrenal tumors that can't be surgically removed and require systemic anti-cancer therapy. The compound is highly radioactive and, once injected intravenously is specifically absorbed by, and then attacks the tumor, while the kidneys flush out the material it doesn't use to kill the tumor cells.
Key to its success is the use of a radioactive pharmaceutical called metaiodobenzylguanidine (MIBG), a compound designed to target only the tumor.
"Essentially, every molecule of MIBG has radioactive iodine (iodine-131) on it. It gets absorbed where you want it to; it irradiates where you want it to, and then it decays," Hunter explained.
While a form of MIBG has been used for years, one of the main stumbling blocks has been to find a method to produce MIBG in which every molecule carries the radioactive isotope. The Hunter lab developed a specific resin that would hold the precursor to the radioactive material until ready to be converted into the radiopharmaceutical for use by the body.
In the lab, it worked exactly as intended. In subsequent years, several compounds were tethered to the resin. Four of these were patented; and one of those four was selected for upscaling, clinical trials and eventual commercialization.
Hunter and grad student researcher Richard Xizhen Zhu, MSc (Chemistry), Ph.D.'99 (Chemistry), who worked on the compound, filed a patent through what was then Western's technology transfer office, which has since become WORLDiscoveries.
At that time, the technology transfer office would get involved in patents only if a company was found to invest in the licensing. But scaling up research involving something highly radioactive – with all the inherent and required procurement, security, and safety protocols – would not be an easy 'get.'
It's a process that requires a lot of resources, and when Molecular Insight couldn't stay financially afloat, it appeared as if the project might be over before its time.
In stepped Progenics Pharmaceuticals, which bought the license and rescued the research, resuming clinical trials at several specialized centers in the United States. Progenics' results confirmed the effects and benefits of the pharmaceutical, now named Azedra (iobenguane 131).
Last week, the FDA approved the drug's use in U.S. patients, under the agency's fast-track program – intended to speed approval of breakthrough drugs – and under its orphan drug program, designed to help commercialize therapy for people with rare diseases. Adrenal cancers affect about 1,000 people in the United States each year.
In a statement, FDA official Richard Pazdur, head of the FDA's Oncology Centre of Excellence, said Azedra provides patients with the first FDA-approved therapy for this specific use. It is shown to decrease the need for blood pressure medication and reduce tumor size in about one-quarter of patients – people who had exhausted all other medical options.
Azedra offers hope to patients who have had little medical reason for optimism
Patrick Therrien, Senior Business Development Manager at WORLDiscoveries, said Hunter's work is an example of how long a product can take to go through the testing, development and approvals process.
WORLDiscoveries has, among other tasks, helped manage and update the patent and licensing agreements during the past several years, although this file pre-dates Therrien's arrival by about two decades.
"This is a major milestone," he said. "It shows, not only do we have the great research going on at Western, we have a mature technology transfer office and can see this thing through."