Monday, Feb 25, 2002
South San Francisco and Berkeley, Calif. -- February 25, 2002 --Genentech Inc. (NYSE: DNA) and XOMA Ltd. (Nasdaq: XOMA) announced that additional results from two Phase III studies of Xanelim (efalizumab) were presented at the 60th annual American Academy of Dermatology meeting in New Orleans, Louisiana. The studies suggest that some patients receiving treatment over 24 weeks with Xanelim, a humanized monoclonal antibody administered by weekly subcutaneous injection, may experience improved response rates compared to the initial 12 weeks of treatment. In addition, some patients may also experience relief from psoriasis symptoms as soon as two weeks after receiving an initial treatment.
Response Rates After 24 Weeks of Treatment
The first presentation focused on results from one Xanelim pivotal Phase III study, in which the effects of Xanelim were studied in adults with moderate-to-severe plaque psoriasis. Mark Lebwohl, M.D., Chairman of the Department of Dermatology at Mount Sinai School of Medicine in New York, presented the first study, which had a primary endpoint of patients achieving 75 percent or greater improvement in Psoriasis Area and Severity Index (PASI) score at 12 weeks of treatment. The study also had secondary, exploratory objectives of observing response rates after 24 weeks of Xanelim therapy.
In the study, 597 patients were randomized to receive weekly subcutaneous doses of 1 mg/kg of Xanelim (n=232), 2 mg/kg (n=243) of Xanelim, or placebo (n=122) for the first 12-week treatment period. At 12 weeks, 258 patients who were either responders (n=119) or partial responders (n=138) were randomized again to receive 2 mg/kg of Xanelim weekly (n=86), 2 mg/kg of Xanelim every other week (n=85), or placebo (n=86) for an additional 12 weeks. Responders were defined as achieving 75 percent or greater PASI score improvement and partial responders were defined as achieving 50 to 74 percent PASI score improvement.
At the end of week 24 of Xanelim therapy in the second portion of the study, 76 percent of the 119 responders during the first 12 weeks of treatment maintained 75 percent or greater PASI score improvement when randomized to receive 2 mg/kg of Xanelim weekly (30 out of 39) or every other week (31 out of 40) for an additional 12 weeks. More than 30 percent of responders had 90 percent or greater PASI improvement from baseline. In addition, 24-week treatment increased the response rate for patients who were partial responders after 12 weeks. Of the 138 partial responders, 53 percent became responders with continued weekly Xanelim therapy of 2 mg/kg (25 of 47) and another 29 percent became responders with continued Xanelim therapy of 2 mg/kg every other week (13 out of 45).
"The study results indicate that 24-week treatment with Xanelim in some cases improves response rates in patients who were only partial responders after 12 weeks of Xanelim therapy," said Dr. Lebwohl. "We look forward to continued evaluation of Xanelim to assess its potential benefits in patients who exhibit a partial response after the first 12-week treatment period."
The most common adverse events (occurring in 10 percent or more of patients) in the first 12 weeks were mild to moderate headaches, infection, chills, nausea, pain and fever following the initial injection of Xanelim. The rate of serious adverse events at 12 weeks was somewhat higher in the Xanelim groups (2 percent) than in the placebo group (0.8 percent). Between 12 and 24 weeks, the most common adverse events (occurring in 10 percent or more of subjects) were nonspecific infection (e.g., common cold), headache, pharyngitis and arthritis. Serious adverse events at 24 weeks included one episode each of allergic reaction, cerebral ischemia, chest pain, diabetes mellitus, bone disorder, exfoliative dermatitis, gastroenteritis, kidney pain, lymphoma-like reaction, peripheral vascular disease, psoriasis, and pulmonary embolus. The rate of serious adverse events at 24 weeks was similar in patients that continued (3.5 percent) or discontinued (3.4 percent) treatment with Xanelim.
Another presentation by Alan Menter, M.D., Chairman of the Division of Dermatology at Baylor University Medical Center, suggested that Xanelim provides an early clinical improvement in patients with moderate-to-severe psoriasis. This presentation was based on data from a pooled analysis of two Xanelim Phase III pivotal trials.
A total of 1,095 patients in the two trials were randomized to receive weekly subcutaneous doses of 1 mg/kg of Xanelim (n=394), 2 mg/kg of Xanelim (n=409) or placebo (n=292). The primary study endpoint was 75 percent or greater improvement in PASI score at the end of 12 weeks of treatment. At week 2, mean PASI score improvements for patients given Xanelim (14 percent improvement in the 1 mg/kg weekly group, and 13 percent improvement in the 2 mg/kg weekly group) improved in comparison to the 8 percent of patients given placebo (n=24).
After 12 weeks of treatment, 29 percent of patients given 1 mg/kg of Xanelim weekly (n=115) and 28 percent of patients given 2 mg/kg of Xanelim weekly (n=113) achieved PASI score improvement of 75 percent or greater versus 3.4 percent of the placebo-treated patients (n=10).
"Psoriasis can be an uncomfortable disease, so the rapid response of Xanelim suggested by this study is very encouraging," said Dr. Menter. "In these studies we saw that within two weeks of initial treatment, patients began to see some relief of psoriasis symptoms."
Xanelim was generally well tolerated. After 12 weeks of treatment, no significant changes occurred in laboratory results or vital signs. The most common adverse events in the Xanelim treatment group (occurring in 5 percent or more of patients) included headache, chills, nonspecific infection (e.g., common cold), pain, fever, asthenia (loss of strength) and accidental injury. Acute adverse events -- mild to moderate headache, chills, fever, nausea, vomiting or myalgia -- occurring within two days of injection were reported in 39 percent of patients receiving Xanelim therapy. These events occurred most frequently with the first dose and decreased with each subsequent dose. By the third dose, overall incidence of acute adverse events was comparable in Xanelim-treated and placebo groups (5.1 percent).
"We are pleased with the results from patients receiving treatment with Xanelim," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations and chief medical officer. "These studies suggest that, if approved by the FDA, Xanelim may provide quick response and continued improvement for patients with moderate-to-severe plaque psoriasis."
Xanelim is a targeted T-cell modulator that is designed to target three key processes in the cascade of events that lead to psoriasis. These targeted processes are: (1) binding of T-cells through interactions with adhesion molecules on the endothelial cell surface; (2) migration of T-cells into the skin; and (3) activation of T-cells, all of which may be linked to the abnormal growth of skin cells and the painful, elevated scaly patches of skin (lesions) typical among psoriasis sufferers.
Genentech and XOMA have completed enrollment in the Xanelim pharmacokinetic study to evaluate pharmacokinetic comparability of the clinical and to-be-marketed Xanelim material. Pending successful study completion, the companies anticipate filing a Biologics Licensing Application (BLA) with the U.S. Food and Drug Administration (FDA) for Xanelim in summer 2002.
Psoriasis is a chronic skin disease that affects more than seven million Americans (about 2.6 percent of the U.S. population), according to the National Psoriasis Foundation. Psoriasis occurs when new skin cells grow abnormally, resulting in thick, red, scaly, inflamed patches. Plaque psoriasis, the most common form of the disease, is characterized by inflamed patches of skin ("lesions") topped with silvery white scales. Psoriasis can be limited to a few spots or involve extensive areas of the body, appearing most commonly on the scalp, knees, elbows and trunk. Although it is highly visible, psoriasis is not a contagious disease. While there are a number of medications that may help control the symptoms of psoriasis, there currently is no known cure.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fifteen of the currently approved biotechnology products stem from or are based on Genentech science. Genentech markets ten biotechnology products directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange under the symbol DNA.
XOMA, Ltd. develops and manufactures innovative biopharmaceuticals for disease targets that include cancer, immunological and inflammatory disorders and infectious diseases. In addition to the Genentech Xanelim collaboration, late-stage programs include collaborations with Baxter Healthcare Corporation to develop NEUPREX® (rBPI-21) for multiple indications (Phase II and III), and Onyx Pharmaceuticals, Inc. to develop and manufacture its CI-1042 product for cancer (Phase II and III). Earlier-stage development programs include compounds for cancer, autoimmune diseases, infections and retinopathies. For more information about XOMA's pipeline and activities, please visit the Company's web site at http://www.xoma.com.
Statements made in this news release related to collaborative agreements and current plans for product development, including the progress of clinical trials and the timing of regulatory filings or that otherwise relate to future periods, are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. These statements are based on assumptions that may not prove accurate. Actual results could differ materially from those anticipated due to certain risks inherent in the biotechnology industry and for companies engaged in the development of new products in a regulated market. These risks, including those related to changes in the status of existing collaborative relationships, the timing or results of pending and future clinical trials, the ability of collaborators and other partners to meet their obligations, market demand for products, actions by the Food and Drug Administration or the U.S. Patent and Trademark Office and uncertainties regarding the status of biotechnology patents, are discussed in XOMA's most recent annual report on Form 10-K and in other SEC filings. Consider such risks carefully in evaluating XOMA's prospects.
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