Hope Put To The Test

Cancer-ravaged patients anxiously wait as EntreMed pursues the first human trials of its drug Angiostatin

April 22, 2001|By Julie Bell | By Julie Bell,SUN STAFF

For Charles Sprenkle, hope comes at the tip of a needle.

Five days a week for precisely 10 minutes, the 62-year-old sits patiently while a large syringe - 6 inches long, 1 inch wide - forces a clear liquid into his forearm.

As a nurse depresses the plunger, the drug flows through his veins deep into his body where - if it works - it will choke the growth of the tiny blood vessels that feed malignant tumors.

Sprenkle, like legions of other cancer victims, has thrown the dice on an experimental treatment. Cancer already has been cut from his tongue and the base of his mouth, which surgeons reconstructed by taking tissue from his chest. A capped tube leading to his trachea juts from his throat. For months, he has eaten primarily by pouring nutrition drinks into a feeding tube in his stomach.

Now his hope is that the drug, Angiostatin - one of a new class of therapies designed to fight cancer without debilitating or even fatal side effects - will spare him further such ravages. Scientists hope drugs like it will make cancer, a scourge expected to kill nearly 554,000 Americans this year, a manageable disease.

Today, The Sun begins an occasional series chronicling the story of Angiostatin as it moves through its first human tests at Thomas Jefferson University Hospital in Philadelphia. The tests, known as clinical trials, are the crucible through which every new therapy must pass to prove it safe and effective. They are arduous, expensive and risky.

Whether Angiostatin proves to be a success or another one of the disappointments that litter the laboratories of drug researchers won't be clear for as many as six more years.

But patients like Sprenkle can't wait. Often frightened and out of options, they are in a desperate race against death.

Neither can EntreMed Inc., a decade-old Rockville company without the deep pockets of a drug giant like Merck & Co. Inc. or Pfizer Inc.

It has no products to sell. It must continue to raise money as it struggles to develop Angiostatin and two similar drugs at once, even as it races to beat nearly 40 rivals to market. The prize is not only hundreds of millions of dollars in profit, but corporate survival as well.

Even Dr. Adam Dicker, Sprenkle's radiation oncologist, fights time. While science moves at an agonizingly slow pace, cancer research is competitive, and scientists like Dicker pursue the kind of breakthrough that builds reputations, wins grants and ignites careers.

Sprenkle is optimistic that Angiostatin will help revolutionize cancer treatment.

"It is my hope," he said, "that they'll be successful at replacing the methods they've used for years - which is slash and burn."

EntreMed scientists

There's always a blue sky in the second-floor board room at EntreMed. It is painted on the ceiling, along with floating clouds and a tiny flock of geese in flight.

It is in this soothing setting that the company's small cadre of top scientists meets Tuesday mornings to coordinate the details involved in getting its drugs to market.

The painting belies the fact that, from the beginning, EntreMed has developed the therapies amid a high-profile storm.

The company licensed Angiostatin and its two other drugs in human testing - Endostatin and Panzem - from Children's Hospital in Boston, where they were discovered in the laboratory of renowned cancer researcher Dr. Judah Folkman. Folkman theorized that microscopic tumors send out chemical signals, starting a cascade of events that result in the formation of tiny blood vessels to feed them.

Process is angiogenesis

If the vessels' growth could be blocked, he reasoned, cancer couldn't grow or spread. He called the process of blood-vessel growth angiogenesis. EntreMed, a name coined by combining the words "entrepreneurship" and "medicine," is a publicly traded bet that anti-angiogenesis drugs will work.

When the New York Times reported on its front page in May 1998 that Angiostatin and Endostatin had resulted in spectacular cancer regression in mice, a sensation ensued. The article quoted Nobel laureate James Watson, co-discoverer of the structure of DNA, as saying Folkman would "cure cancer in two years."

Tiny EntreMed was swamped with phone calls from desperate cancer patients. Its stock soared nearly 330 percent in a day, even though Angiostatin and Endostatin had yet to start tests in people. Ever since, EntreMed has been both haunted and propelled by the fact that it is developing its drugs in a spotlight rather than the obscurity that normally shrouds clinical trials.

The 39 or more companies developing similar drugs aren't pressured by those high expectations.

Those expectations are personified in Watson. A self-described friend of Folkman's and president of the Cold Spring Harbor Laboratory in New York, the elder statesman of biotechnology regularly visits EntreMed. He relaxes on the chaise lounge in the corner of Chief Executive Officer John Holaday's office and peppers the scientist-turned-CEO with questions.

`The heart of Judah'

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