Eden Prairie firm's drug could join arsenal in war on terror

The threat of a nuclear terrorist attack on U.S. soil and abroad looms large at a tiny Eden Prairie pharmaceutical company working on an experimental drug that would treat exposure from radioactive fallout.

Suitcase bombs. Dirty bombs. Accidents or attacks at nuclear power plants. Mass panic. Gridlock. Chaos. The dire scenarios deeply trouble Humanetics Corp. CEO Ronald Zenk.

"Right now, civilians are defenseless in the wake of a nuclear event," he says.

Bolstered by $3 million in Defense Department funding, the privately held company has begun clinical trials in animals and a small number of people testing a drug called BIO 300, which aims to combat acute radiation syndrome (ARS), or radiation sickness.

ARS is a potentially fatal disease caused by a high dose of radiation over a short time, according to the Centers for Disease Control and Prevention. In most fatal cases, the cause of death is the destruction of bone marrow, resulting in infection and internal bleeding.

Humanetics isn't the first company with a potential anti-radiation drug to be courted by the Bush administration, which says it is intent on developing drugs to help the nation defend itself in case of a bioterror attack.

A small San Diego biotechnology firm, Hollis-Eden Pharmaceuticals Inc., spent $85 million over the past decade to develop a similar drug -- only to have the contract canceled by the Department of Health and Human Services. Today, the company's stock price is badly battered and its employee ranks depleted in a recent cutback.

Despite this cautionary tale, Humanetics executives believe BIO 300 has the potential to be approved for treatment of radiation sickness -- which includes damage to the forbears of infection-fighting white blood cells and platelets in bone marrow.

Zenk says that his drug works differently and that the company's broader focus on protecting the civilian population is different, as well. He foresees large companies stockpiling BIO 300, as well as pharmacies and grocery stores; protecting yourself in the wake of a nuclear attack could be as simple as getting a flu shot.

Orphan status

Humanetics cleared an important milestone last month when it was granted an orphan-drug designation from the Food and Drug Administration (FDA). The designation promotes the development of drugs treating rare diseases and conditions -- those typically passed over by large pharmaceutical companies -- that affect fewer than 200,000 people in the United States.

The FDA classification gives companies such as Humanetics seven years of market exclusivity, preventing rivals from developing similar products that siphon away royalties; a 50 percent tax credit for conducting often-expensive clinical trials; and reduced fees for FDA applications.

Although the FDA says the program is successful, the designation doesn't guarantee approval of a drug.

More than 200 drugs and biological products for rare diseases have been approved since the orphan designation was introduced in 1983. Among them: Antizol, used to treat those who have ingested antifreeze, and Acetadote, which mitigates an overdose of Tylenol, which can cause liver damage. (Antizol was marketed by Minnetonka-based Orphan Medical Inc., which was bought by a California company in 2005.)

While Zenk believes the potential market for BIO 300 is "quite large," radiation sickness now is quite rare -- hence its orphan status. The biggest releases of radiation involved the victims of atomic bombs dropped on Hiroshima and Nagasaki during World War II, as well as radiation-related deaths and illnesses associated with the Chernobyl nuclear power plant accident in 1986.

There are drugs now available that treat people exposed to radiation, such as potassium iodide to ward off thyroid cancer. And Prussian Blue, a drug made from blue dye, can remove some radioactive materials from the body, but it must be administered by a doctor.

None of the current remedies protect the body from the damaging effects radiation has on bone marrow, said Dr. John Zenk, Humanetics' chief medical officer and the CEO's first cousin. Ideally, he said, a BIO 300 pill or injection could be taken preventively by the military, first responders and civilians if a radioactive leak has been detected -- especially since people might not know whether they've been contaminated.

Humanetics said it obtained the license for BIO 300 from the Henry M. Jackson Foundation for the Advancement of Military Medicine, a private, not-for-profit organization that supports military research. Terms of the license agreement were not disclosed.

Difficult clinical trials

Testing an anti-radiation drug such as BIO 300 to make sure it is safe and effective brings with it a unique, even daunting, set of challenges.

Because it would be unethical to expose humans to a life-threatening condition such as radiation to test the effectiveness of the drug, the company first tested it on mice, and continues to study it on canines and primates.

While the FDA permits this type of testing, "regulators remain skittish about approving a product based solely on [effectiveness] in animals," according to a 2005 report issued by the American Enterprise Institute for Public Policy Research.

Humans can be used in studies to assess the drug's safety. Humanetics recently completed enrollment in a 24-patient clinical trial at MAPS Applied Research Center in Edina. "We are looking for any adverse event in them; it doesn't have to be related to the drug, it could be a hangnail, but we have to document everything," said Dr. Zenk, who is also the study's principal investigator.

The company will need to conduct a pivotal trial, probably in canines, before seeking FDA approval in 2009.

Yet the drug approval process can be uncertain business. "If it's a drug taken prophylactically, where you give it to people who might be exposed, there has to be really convincing evidence it's safe," said Dr. Daniel Weisdorf, a professor of medicine at the University of Minnesota and director of the U's Adult Blood and Marrow Transplant Program.

Countermeasures to terror

Humanetics was founded in 1988 selling nutritional supplements. Zenk will not disclose financial figures, but says the company has 360 shareholders, including several unnamed investment funds and hedge funds.

After the Sept. 11 terror attacks, the federal government invested $5.6 billion in Project BioShield, a program designed to develop medical countermeasures protecting Americans against a chemical, biological, radiological or nuclear attack. The program gave drug and biotech companies a powerful incentive because it guaranteed a market for successfully tested drugs.

But three years after President Bush signed legislation creating Project BioShield, critics say the program has been plagued by delays and management problems in developing drugs needed to combat bioterror.

Officials at Hollis-Eden have said they are still befuddled as to why its Neumune anti-radiation drug was thwarted. And last year, the government canceled an $877.5 million BioShield contract with a California company called VaxGen Inc. to develop an anthrax vaccine, saying the drug did not meet expected milestones. VaxGen has recently laid off 25 percent of its workforce, and its stock plummeted.

Humanetics is seeking funding from Project BioShield, in addition to its Defense Department appropriation. "[BioShield] is a very good idea," Zenk said. "I think they're struggling with what the top priorities are that we need to protect against. I'm not deterred at all."

Janet Moore • 612-673-7752

Janet Moore • jmmoore@startribune.com