After Japan Crisis, New Urgency for Radiation Drugs

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After Japan Crisis, New Urgency for Radiation Drugs

By ANDREW POLLACK

A flash of blue light signaled the end for Hisashi Ouchi and Masato Shinohara.

It meant that a nuclear chain reaction had started unexpectedly, bathing the two

men in lethal doses of radiation. After they ran out of the room, Mr. Ouchi, who

received the higher dose, briefly lost consciousness, then began vomiting.

But the two men — who were injured in a nuclear fuel accident in Japan in 1999,

not during the current crisis — did not die right away. Drugs and procedures

unavailable when the atomic age began kept Mr. Ouchi alive for 82 days, and Mr.

Shinohara for about seven months.

As radiation spreads in Japan from crippled nuclear reactors, with workers at

the Fukushima Daiichi nuclear plant potentially exposed to extremely hazardous

levels, experts say that progress has been made in developing treatments for

radiation poisoning. But there is still much work to do.

The crisis has put a spotlight on some small biotechnology companies developing

drugs to treat people exposed to radiation. Some say they are accelerating their

efforts in light of the problems in Japan.

Most of the companies are working under contracts from the United States

government, aimed at treating people after a military or terrorist attack

involving a nuclear or radioactive weapon. Such drugs would also be of use in a

nuclear power plant accident, particularly for the nuclear plant workers, who

might be exposed to the highest doses.

" There would definitely be a zone around ground zero where you could save a lot

of people with these drugs, " said Mark H. Whitnall, program advisor for

radiation countermeasures at the Armed Forces Radiobiology Research Institute in

Bethesda, Md.

He said the drugs under development would allow people to survive doses 20 to 40

percent higher than what is now considered lethal. " We'd like to do a lot

better, " he said.

The Japanese crisis has caused upticks in the shares of some of the companies

focusing on this research, like Cleveland Biolabs. Some 5.6 million shares of

Aeolus Pharmaceuticals changed hands on a single day after the crisis began,

over 1,000 times the usual trading volume.

" It was crazy, just crazy, " said McManus, chief executive of the company,

based in Mission Viejo, Calif. In February, it received a federal contract worth

up to $118 million to help it develop a drug to protect the lungs from radiation

damage.

Several of the companies say they want to make their drugs available for use in

Japan, but the government there has not ordered any. The drugs in question have

not been approved by the Food and Drug Administration, and it is unclear whether

anyone in Japan, even workers at the Fukushima plant, have been exposed to

enough radiation to warrant such treatments.

Most of the drugs in development are two to five years away from possible

regulatory approval, federal officials say, and even once approved there would

still be some slight uncertainty about how well they would work in people.

Because it would be unethical to expose people to high levels of radiation in a

clinical trial, the F.D.A. allows approval of this type of drug if it proves

effective in two species of animals and is shown to be safe in people at doses

corresponding to those used in the animals.

Getting federal support for the research is one thing. It might be harder to get

the government to buy large quantities to be stockpiled for use in an emergency.

Hollis-Eden Pharmaceuticals provides a cautionary tale. It was developing a

steroidlike compound that was championed by Defense Department scientists, but

in 2007, after the company spent $85 million on development, the Department of

Health and Human Services decided not to buy the drug, saying it did not meet

technical requirements.

Hollis-Eden's stock price collapsed and has never recovered. The company dropped

the drug and changed its name to Harbor BioSciences.

Some federal officials and experts say that Health and Human Services decided it

needed drugs that could be effective even if given 24 hours after exposure,

reasoning that after a terrorist attack it would be hard to get the drug to

people immediately. The Hollis-Eden drug did not meet that requirement.

The department plans a big purchase, but not of an experimental drug developed

by a tiny company. Rather, it is looking to buy hundreds of millions of dollars

worth of Amgen's Neupogen or a similar drug, including generic versions of

Neupogen that have been approved in Europe, according to Robin ,

director of the department's Biomedical Advanced Research and Development

Authority.

Neupogen helps the body build infection-fighting white blood cells, which can be

depleted by radiation. The drug is approved to help prevent infections in cancer

patients undergoing chemotherapy, but the F.D.A. has issued an " emergency use

authorization " that would allow the drug to be used to treat radiation exposure.

Biodefense work has largely fallen to small biotechnology companies because they

need the money, especially at a time when investors are averse to risk. Federal

grants can help defray the costs of developing a drug for commercial uses. In

the case of radiation treatments, the commercial use would mainly be to protect

cancer patients from the side effects of radiation therapy.

" It's significant funding for a biotech company like ours, " said Ram Mandalam,

chief executive of Cellerant Therapeutics, a private company that won a federal

contract worth up to $153 million over five years to develop a drug using stem

cells to help bolster the immune system after radiation exposure.

Radiation can have various health effects, depending on the dose and form. For

nuclear power plant accidents, the major exposure for the public would come from

radioactive isotopes, and there already are some approved drugs for these that

are in the federal stockpile.

Potassium iodide can help prevent thyroid cancer that can be caused by

iodine-131, which has been detected in some milk, produce and tap water in

Japan. Elevated levels of radioactive iodine have also been detected in milk in

Washington State and California but the levels are still far too low to pose a

health threat, the Environmental Protection Agency said on Wednesday. It has

stepped up monitoring of radiation levels.

Exposure to cesium-137 can be treated with Prussian blue, a pharmaceutical

version of an industrial dye, while plutonium exposure can be treated with DTPA.

Both drugs bind to the isotopes and help the body to excrete them.

The drugs being developed by the biotech companies would probably not reduce the

long-term risk of cancer after radiation exposure. They are aimed more at

treating what is called acute radiation syndrome.

Death from this is often caused by bone marrow failure, which depletes the body

of white blood cells and platelets, which control excess bleeding. The

gastrointestinal tract and other organs can also be heavily damaged.

Progress has been fastest in reconstituting the immune system, using Neupogen,

bone marrow transplants or other treatments. The two workers in Japan overcame

bone marrow failure, only to die later from failure of several other organs.

But bone marrow transplants cannot be done on a mass scale, and even Neupogen is

not ideal if there are thousands of people exposed after an attack because it

requires refrigeration and medical care. So the government is searching for

alternatives.

Cleveland Biolabs, which despite its name is based in Buffalo, is developing a

drug derived from a bacterial protein. It fools the body into believing there

has been a " massive salmonella infection, " said Andrei Gudkov, chief scientist.

The body's response is to produce substances, including the protein in Neupogen,

that help restore the immune system and gastrointestinal tract.

Dr. Gudkov said the drug was at least a year away from approval.

Onconova Therapeutics, a private company in Newtown, Pa., has a drug called

Ex-Rad that facilitates repair of DNA damaged by radiation and helps prevent

cell death.

Osiris Therapeutics has a $224 million contract from the Defense Department to

develop a therapy using stem cells to help repair gastrointestinal injuries. Of

that, $200 million would be possible purchases of the drug, if it is approved by

the F.D.A.

Safety is an obstacle, especially if a drug is to be given to healthy people in

advance of possible exposure. Side effects could also slow down rescue or

cleanup workers entering a contaminated area.

" You do not want to vomit in a hazmat suit, " said E. Moulder, a professor

of radiation oncology at the Medical College of Wisconsin. " You don't really

want to have diarrhea. You want to get in there, get the job done and get out. "

Assessing overall progress, he said, " I think we have moved to show that a

radiological counterterrorism program is medically possible. " But he added: " Are

we ready to go if it's a large number of people? No. "

http://www.nytimes.com/2011/04/01/business/01radiation.html