Promising Phase 3 Trial Results Show Novel Biologic Therapy Ustekinumab (CNTO 1275) Significantly Improved Psoriasis
Three Subcutaneous Doses of Ustekinumab Resulted in Long-term PASI 75 Response and Marked Improvement in Quality of Life Measures According to Study Findings
BUENOS AIRES, Argentina, October 03, 2007 -- The first reported findings from an international, Phase 3 study showed that more than two-thirds of patients with moderate to severe plaque psoriasis receiving two doses of ustekinumab (CNTO 1275) achieved at least a 75 percent reduction in psoriasis at week 12, the primary endpoint of the study, as measured by the Psoriasis Area and Severity Index (PASI 75). Importantly, findings also showed that following one additional dose at week 16, a substantial proportion of patients receiving ustekinumab maintained a PASI 75 response through week 28. Data from the study, presented at the World Congress of Dermatology, involved more than 1,200 subjects and showed that within four weeks of initiating treatment with ustekinumab, patients experienced significant and clinically meaningful improvements in quality of life measures compared with patients receiving placebo. Ustekinumab is a new, fully-human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), and is currently in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis.
These data, presented at the 21st meeting of the World Congress of Dermatology, will be the subject of a live press briefing and webcast (www.cnto1275wcd.com) today at 2 p.m. EDT featuring Craig Leonardi, MD, St. Louis University Medical School, St. Louis, MO, Kristian Reich, MD, Georg- August-University, Gottingen, Germany, Silvia Fernandez Barrio, executive director, Civil Association of Psoriasis Patients of Argentina, Buenos Aires, Argentina, and Tom Schaible, PhD, vice president, Medical Affairs, Centocor, Inc.
"These findings provide further evidence of the role of IL-12/23 in the pathogenesis of psoriasis and the promise that a new therapeutic approach like ustekinumab may hold for dermatologists and their patients living with this chronic, immune-related disease," said Craig Leonardi, MD, St. Louis University Medical School and lead investigator of the study. "The efficacy and safety data for ustekinumab in the treatment of psoriasis are exciting for the dermatology community."
At week 12 of this Phase 3, multicenter, randomized, double-blind, placebo-controlled trial, 67 percent of patients treated with 45 mg ustekinumab (two 45 mg doses four weeks apart) and 76 percent of patients treated with 90 mg ustekinumab (two 90 mg doses four weeks apart), achieved PASI 75 compared with four percent of patients receiving placebo (P < 0.001 for each comparison versus placebo). Also at week 12, 42 percent of patients in the 45 mg ustekinumab dosing group and 51 percent of patients in the 90 mg ustekinumab dosing group achieved PASI 90, or nearly complete clearance of psoriasis, compared with one percent of patients receiving placebo (P < 0.001 for each comparison versus placebo). Similar response rates were observed in the placebo group 12 weeks after crossover to treatment with ustekinumab. After one additional dose at week 16, responses were maintained through week 28, which is consistent with the maintenance regimen of every 12-week dosing currently being evaluated in the Phase 3 program. Improvements in clinical measures were paralleled with improvements in quality of life measures.
"These findings show that by targeting IL-12/23 with ustekinumab, we may be able to offer dermatologists and patients a new, promising biologic therapy with an infrequent dosing regimen for the treatment of psoriasis," said Jerome A. Boscia, MD, senior vice president, Clinical Research and Development, Centocor, Inc. "We are encouraged by the results from the Phase 3 program and look forward to collaborating with regulatory authorities around the world in an effort to bring ustekinumab to physicians and patients in need of new therapeutic options."
Additionally, data will be presented at the World Congress of Dermatology that show that as early as week four patients treated with either 45 mg or 90 mg ustekinumab experienced significant improvements in quality of life measures compared with patients receiving placebo. At week four, according to the Dermatology Life Quality Index (DLQI), a 10-item questionnaire that measures the impact of psoriasis on quality of life and patient burden of disease, median DLQI improvement was 6.0 for 45 mg and 6.0 for 90 mg versus 1.0 for placebo (each P < 0.001 versus placebo). An improvement of five or more from baseline is considered to be clinically meaningful. At week 12, 72 percent of patients receiving 45 mg ustekinumab and 77 percent of patients receiving 90 mg ustekinumab achieved a reduction of at least five points in DLQI score compared with 21 percent of patients in the placebo group (P < 0.001 for each comparison versus placebo). Also at week 12, a total of 37 percent of patients receiving the 45 mg ustekinumab and 39 percent of patients receiving the 90 mg ustekinumab achieved a DLQI score of zero, indicating no impact of psoriasis or the treatment on quality of life, compared with one percent of those receiving placebo (P < 0.001 for each comparison versus placebo). Upon crossing over to treatment with ustekinumab, patients initially randomized to placebo experienced similar improvements in DLQI after 12 weeks.
"Psoriasis is an inflammatory disease that can cause severe emotional, physical and social burdens for patients," said Richard Langley, MD, Dalhousie University, Halifax, Nova Scotia, Canada, and trial investigator. "While more therapies have become available for the treatment of psoriasis over the years, dermatologists need additional options to manage this chronic disease, and ustekinumab would represent a much needed addition in the treatment armamentarium."
About the PHOENIX 2 Trial
The Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial Evaluating the Efficacy and Safety of CNTO 1275 in the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis Followed by Long-term Extension 2 (PHOENIX 2) trial involved 1,230 patients with chronic plaque psoriasis. Patients were randomized to receive subcutaneously administered ustekinumab or placebo. Patients randomized to receive ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4 followed by the same dose every 12 weeks. Patients in the placebo group crossed over to receive either 45 mg or 90 mg doses of ustekinumab at weeks 12 and 16 and every subsequent 12 weeks. The primary end point of the study was the proportion of patients who achieved PASI 75 at week 12.
Through week 12, the placebo-controlled portion of the study, the percentages of study participants who experienced at least one adverse event (AE) were comparable between the placebo group (49 percent) and the ustekinumab 45 mg group (53 percent) and 90 mg group (48 percent). Discontinuation due to an AE occurred in 0.2 percent and one percent of patients in the respective ustekinumab groups, compared with two percent of patients in the placebo group. Two percent and one percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, experienced at least one serious AE compared with two percent of patients receiving placebo.
Psoriasis is a chronic, immune-mediated disease that results from inflammation in the skin and overproduction of skin cells that accumulate on the surface causing red, scaly plaques that may itch and bleed. This chronic inflammation is driven in part by IL-12 and IL-23, cytokines involved in the regulation of the body's immune response. It is estimated that 125 million people worldwide have psoriasis, including two percent of both the U.S. and European populations, or some 7.5 million Americans and 10 million Europeans. Nearly one-quarter of people with psoriasis have cases that are considered moderate to severe.
Ustekinumab is a new, fully-human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis, and is being investigated as an infrequently-administered subcutaneous injection. Ustekinumab is a novel biologic therapy that targets interleukin 12 (IL-12) and interleukin 23 (IL-23), naturally occurring proteins that are important in normalizing the immune system and that are also believed to play a role in immune-mediated inflammatory diseases.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies will market ustekinumab in all countries outside of the United States.
About Centocor, Inc.
Centocor is harnessing the power of world-leading research and biomanufacturing to deliver innovative biomedicines that transform patients' lives. Centocor has already brought innovation to the treatment of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology, Centocor has brought critical biologic therapies to patients suffering from debilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary of Johnson & Johnson.
The Janssen-Cilag companies are members of the Johnson & Johnson Family of Companies, the world's most comprehensive and broadly based manufacturer of health care products, as well as a provider of related services, for the consumer, pharmaceutical, and medical devices and diagnostics markets. Janssen-Cilag companies have a long track record in developing and marketing treatments for central nervous system disorders, pain management, infectious diseases, gastrointestinal disorders and oncology.
(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from the Centocor's and Janssen-Cilag's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2006. Copies of this Form 10-K, as well as subsequent filings, are available online at www.sec.gov or on request from Johnson & Johnson. Neither Centocor nor Janssen-Cilag undertakes to update any forward- looking statements as a result of new information or future events or developments.)