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Genentech and Biogen have drugs in development for psoriasis
Biotech heavyweights Genentech and Biogen are leading a pack of three dozen drugmakers targeting psoriasis.
Most of the research and product development are focused on biologic agents that modulate the immune responses responsible for several forms of psoriasis and psoriatic arthritis.
The intense interest in psoriasis is easy to explain, said Gail Zimmerman, president and CEO of the National Psoriasis Foundation. There are about seven million patients in the United States alone, she said, and existing treatments (methotrexate, cyclosporine, and ultraviolet radiation) can lead to kidney and liver failure as well as an increased risk of melanoma.
"Roughly 60% of patients with psoriasis have dropped out of treatment," Zimmerman said at the Second Joint Meeting of the International Psoriasis Symposium and European Congress on Psoriasis in San Francisco. "These new therapies will offer alternatives that may restore patients' confidence in treatment."
Industry analysts say sales of a safe, effective treatment could top $1 billion annually.
The flood of new products in the development pipeline stems from discoveries that psoriasis is an autoimmune disease mediated by T cells. The most common form of the disease, plaque psoriasis, is the result of overproduction of skin cells. Excess cells accumulate as itchy, scaly plaques that can impact quality of life as dramatically as hypertension, diabetes, and cardiac disease.
Researchers are trying to disrupt development of psoriasis. Some companies have targeted wayward T cells. Others are trying to inactivate tumor necrosis factor-alpha (TNF-alpha), a major component of the inflammatory process, and other key steps in the disease process.
Neither of the most-promising products, Xanelim (efalizumab)a monoclonal antibody developed by Genentech and Xomaand Amevive (alefacept)a fusion protein from Biogenhas been approved by the Food & Drug Administration. Biogen expects to submit alefacept later this year. Genentech said it will submit efalizumab late this year or early in 2002.
Both companies released phase III trial data in San Francisco.
Genentech reported that 39% of its patients showed at least a 75% improvement in their psoriasis after 12 weeks of treatment, compared with 2% of patients who received placebo. Side effects included moderate headaches, chills, and fever. Genentech said the side effects subsided after the initial dose.
Biogen said that 21% of patients who received weekly injections of alefacept saw a similar 75% improvement in their disease after 12 weeks. The 75% response rate jumped to 40% for patients who received two 12-week courses of the drug as a 30-second IV push.
The most common adverse events in Biogen's trial were accidental injury, headache, pruritus, minor infections (common colds and folliculitis), pharyngitis, and rhinitis. There was no statistically significant difference in adverse events between the alefacept group and the placebo group, according to Biogen medical director Daniel Shrager, M.D.
"Both of these drugs have very convincing data on efficacy in psoriasis," said Mark Lebwohl, M.D., head of dermatology at Mount Sinai Medical Center in New York.
But they are not identical. Efalizumab is designed to suppress psoriasis with regular use. The disease recurs in half of patients two to three months after stopping treatment.
Alefacept is designed as a remittent therapy. Patients have remained symptom-free for up to 18 months after treatment ended, Shrager said. The median duration of response is 10 months.
"The range of products represents a remarkable diversity of approaches," Lebwohl said. "If one line of therapy proves to be less effective, or is poorly tolerated, there will be other approaches available."
A few of those other approaches are already available. Remicade (infliximab, Centocor), which is indicated for Crohn's disease and rheumatoid arthritis, is showing promising results against psoriasis, said Alice Gottlieb, M.D., professor of medicine at Robert Wood Johnson Medical School. The drug binds to TNF-alpha.
A phase II trial showed that 80% of patients had at least a 75% improvement in psoriasis within 10 weeks of starting treatment. That makes infliximab the only biologic that can match cyclosporine in clearing the signs and symptoms of psoriasis.
The potential downside, according to researchers, is that infliximab suppresses the immune system, which may leave patients susceptible to tuberculosis and sepsis. Cyclosporine can damage the liver in long-term use.
Immunex is also targeting TNF to treat psoriasis and psoriatic arthritis. Nearly one-quarter of patients receiving Enbrel (etanercept) showed at least 75% improvement in psoriasis, while 87% had significant improvement and reduction of joint pain and swelling due to psoriatic arthritis. The phase III trial lasted nine months.
Fred Gebhart. Two biotech companies lead attack on psoriasis.