Encouraged by the results of clinical tests that were to be released today, Human Genome Sciences Inc. will expand human testing of a protein designed to promote wound-healing, marking an advance for one of the first drugs developed with a system that uses computers to find genes that give rise to therapeutic proteins.
The system is known as genomics-based drug discovery, and Human Genome is betting that it will be superior to the less precise approach pharmaceutical companies traditionally have used to find drug candidates.
To date, the approach has yielded four gene-based drugs in various stages of human testing for Rockville-based Human Genome Sciences. But until today, when results for human testing of its protein therapy for skin ulcers were to be released at a scientific conference in Australia, none had advanced far enough to determine whether they showed clear signs of effectiveness as treatments.
Now, some industry analysts and the company say, clinical trial results for repifermin provide an early barometer of how well genomics-based discovery works. The drug, a naturally occurring human protein, was shown in the trials to be free of side effects and to accelerate wound-healing in patients with lower-leg skin ulcers related to varicose veins.
The trial, which involved 94 patients at 15 centers, showed that significantly more patients treated with repifermin had wounds that experienced at least 75 percent closure in 12 weeks compared with patients treated with a placebo.
"This trial is a window into the future," said Dr. David Steed, a University of Pittsburgh surgery professor who oversaw part of the clinical trials of repifermin as a treatment for venous ulcers. "Repifermin is promising, and the system is promising. This may be the first you'll see of something that could become commonplace."
David C. Stump, the company's senior vice president of drug development, said the trial "has to be viewed as an important step to validating this discovery process."
But others said it may be too early to draw that conclusion. John McCamant, editor of Medical Technology Stock Letter, noted that other companies also are spending millions to pursue gene-based drug discovery. He said yesterday, before the clinical trial results' release, that, "We don't see any evidence that Human Genome Sciences is doing this better than anyone else. ... They're really just getting going in the drug development business."
Up to 700,000 patients in the United States and a similar number in Europe suffer from venous ulcers, the company said. They result when malfunctioning veins cause blood to pool in the veins of the lower leg, causing skin deprived of oxygen from freshly circulated blood to deteriorate. Such patients, who often are elderly and can have other health problems, have few options other than compression bandages, salves and changes of dressing to treat wounds that can remain open for years.
Human Genome developed repifermin through a process that turned drug discovery on its head. Traditionally, biotechnology companies focused on a problem happening in the body, then - using experiments - looked for a single protein that may be able to stop or reverse it. Once they found a protein that might work, they generally stopped looking at others and began testing it in the laboratory, in animals and, eventually, in human clinical trials required by the Food and Drug Administration to determine if it is safe and effective.
But Human Genome Chief Executive Officer William A. Haseltine thought this method might ignore even better naturally occurring therapies. To find them, the company set out to identify all the genes that give rise to the body's signaling proteins - those that control the behavior of human organs and cells. Then it determined chemical recipes for each gene and used the recipes to make small amounts of each gene's protein product. Ultimately, the method allowed Human Genome to build a library of thousands of signaling proteins and information about their functions - information its scientists quickly could cull using computers when trying to identify the best protein therapy for a specific illness.
Craig West, an analyst for A. G. Edwards & Sons, said the old method of looking for drug candidates was much like selecting a book out of the library for a research project, without knowing what other books were there to determine if another one was better. Compared with Human Genome's systematic method, older drug-discovery methods are "just a hunt for a needle in a haystack without a magnet," West said.
But whether repifermin will work to close skin ulcers well enough to gain FDA approval is yet to be seen. (The company also is testing the drug to determine if it can heal mucositis, chemotherapy-related wounds that often occur in the mouth, as well as ulcerative colitis.)
Human Genome Sciences said yesterday that results of its Phase II trials, the second of three phases of human testing required by the FDA, were promising enough to move to a much larger Phase IIB trial. Stump said the trial likely would enroll more than 600 patients at 50 to 60 centers and look at whether repifermin promotes complete closure of wounds.
But McCamant said wound-healing drugs traditionally have been tough to usher through the final stage of clinical trials. Many times, he said, wound patients receiving placebos also improve with the top-notch care and attention given all patients in clinical trials, regardless of whether they are getting a real drug or a placebo.