Centocor, Inc. Releases Phase 2 Data on Novel Biologic CNTO 1275 Targeting Chronic Plaque PsoriasisPhase 2 Study Results Published in New England Journal of Medicine Show Significant and Sustained Improvements in Skin and Dermatology-Specific Quality of Life Measures
HORSHAM, Pa., February 07, 2007 /PRNewswire/ -- Phase 2 data published today in the New England Journal of Medicine showed that patients with moderate to severe plaque psoriasis receiving subcutaneous injections of CNTO 1275 (IL-12/23 mAb) experienced significant clearance of skin disease and significant improvements in quality of life. At week 12 of the study, 81 percent of patients receiving four weekly 90-mg doses of CNTO 1275 achieved at least 75 percent improvement in their psoriasis, as measured by the Psoriasis Area Severity Index (PASI 75), compared with two percent of patients receiving placebo. In addition, significantly more patients in each of the three additional CNTO 1275 dosing groups achieved at least a PASI 75 improvement in their psoriasis versus patients receiving placebo. CNTO 1275, a fully human monoclonal antibody that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), is currently in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis.
"Research findings continue to provide a deeper understanding into the clinical pathway of psoriasis, which we hope will lead to the development of additional therapies, like CNTO 1275, and broaden the range of treatments available to physicians and patients," stated Gerald G. Krueger, MD, University of Utah, Salt Lake City, UT and lead author. "At week 12 in this investigational study, the majority of patients treated with CNTO 1275, regardless of dosing, experienced significant skin clearance and sustained improvements in physical, emotional and social well being."
Researchers believe that abnormal immune responses, mediated by type 1 T-helper cells, play a key role in the development of psoriasis. IL-12 and IL-23, naturally occurring proteins that are important in regulating the immune system, stimulate type 1 T-helper cells' responses. Preclinical studies suggest that blocking IL-12 and IL-23 may therapeutically benefit psoriasis patients, and CNTO 1275 has been shown to effectively block IL-12 and IL-23 interactions with the surface of immune cells.
At week 12 of the study, among patients receiving CNTO 1275, 81 percent receiving four weekly 90-mg doses, 67 percent receiving four weekly 45-mg doses, 59 percent receiving a single 90-mg dose and 52 percent receiving a single 45-mg dose achieved a PASI 75 response, versus two percent of patients receiving placebo (P < 0.001 for each comparison). Among patients receiving CNTO 1275 in the outlined dosing groups, 52 percent, 44 percent, 30 percent and 23 percent achieved PASI 90, or almost complete skin clearance, versus two percent of patients receiving placebo (P < 0.001 for each comparison). Moreover, a proportion of CNTO 1275-treated patients receiving four weekly 90-mg doses (20 percent), four weekly 45-mg doses (16 percent), a single 90-mg dose (16 percent) or a single 45-mg dose (five percent) achieved total skin clearance (PASI 100). Significant improvements in PASI scores were observed in patients receiving CNTO 1275 as early as week 2, with further improvements through 24 weeks.
"Centocor is committed to the research and development of novel biomedicines with a focus on bringing additional treatment options to dermatologists and patients," stated Jerome A. Boscia, MD, Senior Vice President, Clinical Research and Development, Centocor, Inc. "Centocor has already brought innovation to the field of dermatology through anti-tumor necrosis factor alpha (anti-TNF-alpha) therapy, and it is our hope that the continued clinical program for CNTO 1275 targeting IL-12 and IL-23 will bring innovation and a therapeutic option in a disease area in which unmet needs in treatment continue to exist."
Similar proportions of patients receiving CNTO 1275 and showing improvement in PASI were assessed as being clear or having an excellent response using the Physician's Global Assessment score (PGA). PGA documents physicians' overall evaluation of a patient's psoriasis relative to baseline and considers the percent of body surface area coverage. Efficacy in placebo-treated patients who crossed over at week 20 to receive a single 90-mg injection of CNTO 1275 mirrored the improvements observed in patients randomized to receive a single 90-mg dose of the monoclonal antibody at baseline, as measured by improvements in PASI and PGA scores.
At week 12, all patients in the study completed a Dermatology Life Quality Index (DLQI) questionnaire, a 10-item questionnaire that measures the impact of psoriasis on quality of life and improvements in patient burden of disease. Meaningful improvements were seen in all groups treated with CNTO 1275 (P < 0.001 for each comparison versus placebo), and significant proportions of patients in all CNTO 1275 treatment groups reported at week 12 that neither their psoriasis nor the treatment had a measurable negative impact on their quality of life, as indicated by a DLQI score of zero (P < 0.001 for each comparison versus placebo). Similar results were observed at week 24.
About the Study
In this 52-week, double-blind, placebo-controlled trial, 320 patients with plaque psoriasis for at least six months, at least 10 percent body surface area involvement and a PASI score of at least 12, and who were candidates for phototherapy or systemic therapy, were randomized to receive one of four dose regimens of CNTO 1275 (a single dose of 45 mg or 90 mg or four weekly doses of 45 mg or 90 mg) or placebo. Patients randomized to receive CNTO 1275, whose PGA scores were less than excellent, received a single additional dose at week 16. Patients in the placebo group crossed over to receive 90 mg of CNTO 1275 at week 20.
In the trial, through week 20, 79 percent of patients receiving CNTO 1275 compared with 72 percent of patients receiving placebo experienced adverse events (AEs) after an average of 19.7 and 17.9 weeks, respectively. Forty-three percent of patients receiving CNTO 1275 experienced an infection compared with 39 percent of patients receiving placebo. Rates of AEs and infections in the CNTO 1275 groups were not dose dependent. Serious AEs resulting in hospitalization were observed in four percent of patients receiving CNTO 1275 compared with one percent of patients receiving placebo. The most common serious AE was myocardial infarction, occurring in two CNTO 1275-treated patients. Malignancies were reported in two percent of CNTO 1275-treated patients and two percent of placebo-treated patients. The proportions of patients experiencing significant abnormalities in hematology and chemistry laboratory values were low and similar between groups receiving active treatment and placebo, though a nonsignificantly greater proportion of patients treated with CNTO 1275 experienced elevated nonfasting glucose levels compared with placebo-treated patients. Injection site reactions occurred in three percent of placebo injections compared with two percent of CNTO 1275 injections.
Psoriasis is a chronic, immune-mediated disease, which 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. Interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in regulating the immune system, stimulate immune responses that play a key role in the development of psoriasis. Preclinical studies suggest that blocking IL-12 and IL-23 may therapeutically benefit psoriasis patients. It is estimated that two percent of the U.S. population has psoriasis, and about 30 percent of people with psoriasis have cases that are considered moderate to severe.
About CNTO 1275
CNTO 1275 is a fully human monoclonal antibody in Phase 3 development by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis. CNTO 1275 targets interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in regulating the immune system but are also believed to play a role in inflammatory diseases.
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.
CONTACT: Michael Parks, Centocor, Inc., Phone: +1-215-325-4010, Mobile:+1-215-983-8000
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Posted: February 2007