Cancer Drug

Guilford Pharmaceuticals Inc. said yesterday that the Food and Drug Administration had rejected its request to expand the use of its Gliadel brain-cancer treatment, providing the latest setback for the company and pushing its shares down 15 percent. The stock of the Baltimore-based company traded as low as $6.50 yesterday before rallying to close at $8.14 on the Nasdaq stock market, down $1.49 for the day. The closing price, a six-month low, left the stock nearly 45 percent below its six-month high of $14.76 on Nov. 20. Chief Executive Officer Craig R. Smith said in a conference call that Guilford is seeking a meeting with the FDA about the agency's decision to reject the use of Gliadel in initial brain-cancer surgeries.

EntreMed Inc.'s David Jackson is under the gun. The small Rockville company is moving its anti-tumor drugs into more tests in ever larger groups of patients, and Jackson is at the fulcrum of a multimillion-dollar balancing act. His task: ensuring that the company has enough of the delicately made protein drugs. For the past two years, the EntreMed vice president in charge of manufacturing has scrounged increasingly scarce space at contract manufacturers to make the drugs. Sometimes, he has nailed down an agreement just in the nick of time.

RU CHIH HUANG is a 69-year-old academic, barely five feet tall, with a soft, round face, quiet voice - and ferocious determination to fight. A survivor of the "Rape of Nanking" in China during World War II, Huang immigrated alone to America when she was young and overcame isolation, limited English skills and skepticism to earn her doctorate in biology. In 1965, she became the first female science professor at the Johns Hopkins University. Now, nearing the end of her career, she's fighting to regain a reputation that took four decades to build.

Gliadel, Guilford Pharmaceuticals Corp.'s chemotherapy-packed wafer, benefits patients who receive it during initial surgery for brain cancer, an expert panel that makes recommendations to the Food and Drug Administration found yesterday. The $10,500 surgically implanted wafer currently is approved for use only with a certain kind of aggressive brain tumor that has recurred, requiring a second surgery. FDA approval of its use in initial surgeries would roughly triple the market for Gliadel, which generated nearly all of Guilford's $5.9 million in third-quarter revenue.

EntreMed Inc. said it began a clinical trial yesterday in which cancer patients are injecting themselves at home with the anti-tumor drug Endostatin. The trial, for patients with neuroendocrine tumors, is the latest step in the company's attempt to develop cancer drugs that are free of side effects. The aim is to make cancer a manageable disease, much like diabetes. EntreMed expects 32 patients to enroll in the Endostatin trial at Dana-Farber Cancer Institute in Boston. The Phase II trial, focused on measuring the drug's effectiveness, is the second of three phases of human testing required by the Food and Drug Administration.

Peggy Klang has let go of the hope that the experimental drug will save her from the tumor threatening her windpipe, or the others lodged in her abdomen, neck and lungs. Instead, she spends much of the energy she has left fighting pain and preparing for her own death. Charles Sprenkle once hoped the same drug, being developed by EntreMed Inc. of Rockville, would help prevent a recurrence of the mouth cancer that resulted in the removal of part of his tongue. But a cluster of cancer cells sprang up in his neck despite radiation and low doses of the drug, Angiostatin, taken in an early-stage test of its safety at Thomas Jefferson University Hospital in Philadelphia.

The Johns Hopkins University is investigating a researcher who tested an experimental anti-cancer drug on patients in India without seeking the permission of an internal review board that considers the safety of human studies, a spokesman said yesterday. The experiment, which was conducted on 26 patients in 1999 and 2000, sought to determine whether a chemical derived from the creosote plant could stop the growth of oral cancer. Ru Chih C. Huang, a Hopkins biology professor, said yesterday that she did not submit her study to a Hopkins review board because it was approved by a similar panel at the Indian cancer center where the trial was performed.

EntreMed Inc. said yesterday that it had begun more advanced human tests of its anti-cancer drug Endostatin, seeking to gauge its effectiveness as well as its safety. The clinical trial at M.D. Anderson Cancer Center in Houston will involve up to 30 patients who will receive Endostatin via continuous infusion, a method that pumps the drug from a small, wearable cassette into the patient. While patients with a number of different tumor types will be accepted, EntreMed President Edward R. Gubish Jr. said about half will have sarcoma or melanoma, cancers in which Endostatin showed signs of promise during earlier trials focused on safety.

EntreMed Inc. Chairman John Holaday stepped onto the ballroom dais in San Francisco's fashionable Argent Hotel, his eyes taking in the empty chairs surrounding two of the eight tables, a less-than-flattering newspaper headline of that morning still rankling. His company had spent weeks planning to make this private luncheon for stock analysts an upbeat affair, one designed to help the Rockville company raise needed cash. EntreMed had star billing before the 25,000 scientists, analysts and others gathered in the city for the world's largest conference on cancer treatment, and independent scientists had described results from early human tests of its anti-cancer drugs as promising.

SAN FRANCISCO - Shares of EntreMed Inc. fell nearly 21 percent yesterday after results of the first human tests of its two anti-tumor drugs failed to ignite investors' enthusiasm. The scientific presentations Sunday and yesterday at the American Society of Clinical Oncology's meeting here marked the first release of complete results from Phase I clinical trials for Endostatin and Angiostatin. Investors reacted negatively, despite what the company and independent scientific investigators described as positive results.