Suburban drug company devotes energy finding a cure

In rural regions of sub-Saharan Africa, the blood-sucking tsetse fly can carry a rather ghastly parasite.

If an infected fly bites you, the trypanosome parasite will multiply in your blood and lymph systems, causing waves of fever and headache. Eventually the protozoa will infect your brain, keeping you awake all night and drowsy all day.

Without treatment, victims of what is known as "sleeping sickness" go into a deep coma and die.

The World Health Organization estimates African sleeping sickness affects 50,000 to 70,000 people a year. To a drug company, that's small potatoes. And so the disease remains under-funded and under-researched.

A small drug company in Vernon Hills is trying to change that.

Phase III clinical trials are under way in the Democratic Republic of Congo, Sudan and Angola for pafuramidine maleate, the leading drug candidate of suburban Immtech Pharmaceuticals.

Earlier this month, the U.S. Food and Drug Administration granted orphan drug status to pafuramidine for the treatment of African sleeping sickness. The designation brings some marketing and regulatory benefits to Immtech. It also adds to the local company's momentum toward introducing its first drug on the market, which could happen in 2008 or 2009.

Global health is big news these days, whether you're talking about avian influenza or a wayward tuberculosis patient. Investors now are more willing to support a pharmaceutical firm developing a drug that targets markets outside the U.S., said Cecilia Chan, Immtech's executive director.

"More investors have a global health awareness," she said. "We are finding we are getting more institutional investors and a new wave of retail investors."

So far, Immtech hasn't rewarded those investors. Reflecting the cost associated with drug development, Immtech posted $2.79 million in net losses for the three months that ended June 30. And it's not going to reap big profits selling a drug treating African sleeping sickness.

However, eventually pafuramidine could be useful for other diseases with greater profit potential.

Phase III clinical trials are testing pafuramidine against pneumocystis pneumonia -- or PCP -- a common infection in people whose immune systems are weakened by treatments for cancer, organ transplants or AIDS. Immtech hopes its drug will be as effective as current medications, but with fewer side effects.

This summer, Immtech reached a $32 million deal with Par Pharmaceutical Cos. Inc. to market pafuramidine for PCP in the U.S. Immtech received an initial payment of $3 million and will get the rest as the drug advances through the FDA approval process. In addition to royalties, Immtech could also receive up to $115 million based on sales milestones.

"That deal alone will pay back a substantial portion of all the investment in the past 10 years," Chan said.

Chan estimates Immtech has spent less than $70 million in drug development for pafuramidine over the past decade. That's dramatically lower than the industry standard of $500 million to $800 million to get a new drug to market.

A new model

Instead of supporting its own research and development staff, Immtech partners with university scientists to investigate drug compounds. To fund clinical trials, it works with government and nonprofit foundations; the Bill and Melinda Gates Foundation has awarded more than $60 million in grants to Immtech's scientific partners at the University of North Carolina at Chapel Hill.

The company itself has just 28 employees.

One of them is Carol Olson, an M.D. and infectious disease expert who left Abbott in 2004 to become Immtech's chief medical officer. A few years earlier, she heard a speech by Jimmy Carter on eradicating Guinea worm disease in Africa.

"I came home and told my husband someday I would like to do something like that," said Olson, who lives in Lindenhurst and works with other members of Immtech's clinical staff in Vernon Hills. "For a number of years I had been trying to figure out how we as a society could develop drugs for critical infectious diseases, where the market was not big enough for 'Big Pharma' to get involved. I was very frustrated."

At Abbott, Olson targeted drugs with a market of $500 million in annual sales. As a small company without a large infrastructure to support, Immtech can develop drugs with significantly smaller markets.

"We can develop drugs that are really needed by patients, but aren't going to sell billions of product," Olson said. "Millions will still make us very profitable."

Where pafuramidine could really pay off is as a preventive drug against malaria. Every year, roughly 125 million people travel from developed countries to malaria-infested regions; a course of malaria prophylaxis costs $85 to $150.

"That is a billion-dollar market potential," said Chan. "For us to get a portion of that market will be hugely profitable."

Immtech is testing pafuramidine against malaria in a phase II study, in which healthy volunteers are intentionally exposed to mosquitoes infected with malaria. Immtech hopes to win FDA approval to use pafuramidine in pregnant women and children, who are at higher risk of infection and complications from malaria.

A Trojan horse

As an oral drug that is less toxic than other therapies for African sleeping sickness, pafuramidine has the potential to help people in remote areas. It's easier to administer than the current regimen of intravenous drugs.

"If you can get in and diagnose people with early stage disease, screen people where tsetse flies are, you could almost eliminate this disease with this drug," said Richard Tidwell, professor of pathology at University of North Carolina at Chapel Hill, who is leading the clinical trials for Immtech.

The drug works against African sleeping sickness, or trypanosomiasis, by mimicking some of the nutrients parasites need to survive, Tidwell said. Once the parasite absorbs the drug, Trojan horse-style, pafuramidine kills its host by multiple means, making it less likely the parasite could develop resistance.

"Hopefully this drug is going to have a huge impact," Tidwell said. "This is the first new drug for early-stage trypanosomiasis in 50 years, and it's the first oral drug for any stage of trypanosomiasis."

Pafuramidine has a major drawback: it only works against the disease's early stage. It's not effective once the parasites have crossed into the nervous system.

Tidwell and other scientists are working on the next generation of drugs that could pass that barrier.

"The home run is going to be developing a drug that works against early and late stage disease," said Tidwell. "I think we're very close."