Systemic lupus erythematosus is a potentially fatal disease that develops when the body's immune system runs wild and attacks the kidneys, heart, lungs, brain, blood or skin. Shortly before lupus killed her, the writer Flannery O'Connor wrote: "The wolf, I'm afraid, is inside tearing up the place."
Lupus strikes differently from patient to patient, making it difficult for drug companies to demonstrate the widespread therapeutic effects required by the Food and Drug Administration. That has left lupus patients with few options, including high doses of steroids and cancer drugs that have toxic side effects and leave bones dangerously brittle.
Human Genome Sciences executives -- from left, Craig A. Rosen, Vivian R. Albert, William W. Freimuth, David M. Hilbert and David C. Stump -- gather around a sculpture based on BLyS at company headquarters in Rockville.
(Katherine Frey -- The Washington Post)
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While some biotechnology and pharmaceutical companies are close to selling drugs that treat the side effects of established lupus therapies and of kidney disease caused by lupus, only a few, led by Genentech and Human Genome Sciences, are targeting the mechanics of the disease itself.
Genetech's potential lupus drug is Rituxan. Its edge in the race to market is that the drug is already used to treat non-Hodgkin's lymphoma, a form of cancer, so the Food and Drug Administration already has found it biologically active in the body and safe. But advanced drug trials on its effectiveness in treating lupus have not yet begun.
Human Genome Sciences' drug, LymphoStat-B, is in advanced testing on almost 500 lupus patients across the country. The drug also has been given fast-track status by the FDA, meaning it gets special attention. If advanced human testing results, expected in the fall of 2005, were to show the drug was strikingly successful, Human Genome Sciences could ask the FDA to approve LymphoStat-B without another round of tests.
For Human Genome Sciences, the first step toward developing a lupus drug came in the late 1990s, when company biologist and vice president of research David M. Hilbert led a team that discovered a key protein called BLyS, which is required for disease-fighting cells to mature and produce antibodies to attack viruses and bacteria.
Some disease-fighting cells go bad, producing antibodies that can attack the body instead. Normally, the body kills those bad cells. Research by Human Genome Sciences and others have shown that too much BLyS causes so much cell activity that the malicious antibodies thrive and start attacking the body. "The right amount of BLyS is a good thing," Hilbert said. "Too much of a good thing is a bad thing."
So in collaboration with Cambridge Antibody Technology Group PLC, a British company, Human Genome Sciences developed LymphoStat-B, a human antibody that attaches to BLyS and inhibits stimulation of disease-fighting cells so the body can resume its normal process of killing cells that go bad.
In contrast, Genentech's Rituxan directly attacks the body's disease-fighting cells, then counts on the stem cells in bone marrow to generate new ones without creating too many of the bad cells.
As Human Genome Sciences developed its approach to lupus, it ventured beyond its headquarters to work with key constituencies in academia and advocacy.