The race to bring to market the most important new drug to treat lupus in 40 years hardly seems an even match.
Genentech Inc. of South San Francisco, Calif., has 13 drugs on the market and calls itself "the founder of the biotechnology industry." It had revenue of $3.3 billion last year.
Its chief competitor, Human Genome Sciences Inc. of Rockville, has raised a more than a billion dollars but has yet to bring a single drug to market. Two of its drugs have flopped, and its stock has slumped from $109 a share four years ago to less than $11. It had revenue of $8.2 million last year.
Yet experts say the race between the biotech companies to develop a new drug for an agonizing disease that affects 1.5 million people in the United States alone is hard to handicap. "You can't really say yet," said John T. McCamant, editor of the Medical Technology Stock Letter, which tracks dozens of biotech firms and treatments.
Executives at Human Genome Sciences say their first concern is helping those with lupus, but they don't deny the pressure to be first to offer a new drug that could generate several hundred millions of dollars a year in sales.
"Our goal is to develop well, but to also develop fast and be first," said David C. Stump, the company's executive vice president of drug development.
On the surface, the race is being waged by researchers in laboratories and by medical personnel running drug trials. But it is also a contest of coalition building, marketing and prestige as the companies work to impress academic experts and win over patient-advocate organizations.
"You've got to convince the world out there -- and by the world, at a minimum you're talking about the patients who have to participate in trials and the investigators who have to conduct them -- that you have something that's got a decent chance of altering the disease," Stump said.
The campaign for credibility is aimed in part at casting the biotech company's interests as more than commercial. But the net effect of the courting is commercial.
"What you're doing is establishing a market," said Edward A. Tenthoff, an analyst with Piper Jaffray.
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.
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.
The annual meetings of the American College of Rheumatology is important for potential lupus drugs because rheumatologists are the front-line care providers for lupus patients. The meetings are watched by Wall Street analysts and experts as well.
"The conferences are where you're getting your actual data," McCamant said. "If I get there and see actual data that something is working, that's when I go 'wow,' that's when things get exciting. And that's when the market reacts. At the conferences, that's where you're creating more sustainable value."
Four years ago, Human Genome scientists traveled to Philadelphia with some of their academic collaborators for the meeting, at which they presented findings indicating that too much BLyS plays a role in lupus.
Last September, the company went to the rheumatology meeting to present results showing that, in initial human testing, LymphoStat-B was well-tolerated and significantly reduced levels of circulating disease-fighting cells.
The announcements did not help the company's stock price. In fact, it fell nearly $8 a share the day of the first announcement, though company officials maintain that the conference presentations increased their credibility in the scientific community.
At next month's rheumatology meeting, Human Genome Sciences will also be well-represented, although company officials said they plan no major announcements.
Genentech presents at a number of scientific conferences, including the rheumatology meetings, at which the company has disclosed test results for treating rheumatoid arthritis with Rituxan and plans to do so again next month. The company is also planning a symposium on the potential role of disease-fighting cells in arthritis.
Human Genome Sciences also has worked to cultivate a relationship with the Lupus Foundation of America Inc., the largest and most influential advocacy group for lupus patients. The foundation closely examines potential treatments and sometimes allows its views to be quoted in company news releases, which are distributed to analysts and, through the foundation, to patients around the world.
"These companies need credibility," said Susan M. Manzi, co-director of the University of Pittsburgh Lupus Center of Excellence. "For one thing, if you can't get patients into your studies, then you're done. You have no chance at developing your drug." She said patients with lupus, which usually is not fatal in the short term, may be less likely to try a drug that has uncertain results than patients, such as those with end-state cancer, who face near-certain death.
"And that's really in the end what we've looked for," Stump said. "The stamp of credibility to the patient community that says 'This is a real possibility, you should strongly consider being part of this trial.' " In July, when Human Genome Sciences had enrolled 449 patients in its advance tests, Sandra C. Raymond, president of the Lupus Foundation, publicly spoke of the research. "The LymphoStat-B Phase 2 clinical trial is one of the largest ever conducted in lupus patients, and we will be following it with great interest," she said in a news release issued by the company.
Raymond said the foundation gets a fair return for its work with the biotech firm.
"We'll help a company recruit for trials," Raymond said. "Our role is to hold out hope.
"Who is going to bring this disease under control?" she said. "It's the companies. They can bring it under control. We want that."
Genentech, perhaps because of its greater size and success at developing drugs, sees the Lupus Foundation's role differently.
"They're really not there to enroll patients but to inform the public about the disease," said Andrew C. Chan, Genentech's vice president of research for immunology. To that end, the company's medical director gave a presentation about its efforts to develop a lupus drug at the foundation's World Lupus Day in May. Human Genome Sciences also presented at the event.
Winning isn't necessarily the only thing in the race to bring a lupus drug to market. Elise Wang, an analyst with Smith Barney Citigroup, said there's plenty of room for second- and third-place finishers to do well.
There remains the biggest unanswered question: Will either Genentech or Human Genome Sciences produce a drug that really works against lupus?
The giant California company could more easily absorb a failure. Genentech sees Rituxan as one element in a planned suite of immunology drugs.
Craig A. Rosen, Human Genome Sciences' president of research and development, said it would be difficult to determine how much money his company has spent on developing its drug, and, in any case, he wouldn't disclose such a figure.
But he said executives aren't betting the company on the lupus drug -- despite the giant sculpture of BLyS, designed by the daughter of the company's outgoing chief executive, that is the centerpiece in the foyer of the headquarters.
"We'd love to have this drug work but we have many things in the pipeline," including drugs for cancer, hepatitis, and anthrax attacks, Rosen said. "Hopefully we're due now for a few that will work."