SAN ANTONIO, TX, February 2, 2008 -- One-year data from a second double-blind, placebo-controlled Phase 3 study showed therapy with ustekinumab given every 12 weeks provided sustained, clinically meaningful improvement in the treatment of moderate to severe plaque psoriasis through one year. According to findings presented at the Annual Meeting of the American Academy of Dermatology, 87 percent of patients responding to ustekinumab 45 mg maintenance therapy and 91 percent of patients responding to ustekinumab 90 mg maintenance therapy sustained at least a 75 percent improvement in psoriasis through one year, as measured by the Psoriasis Area and Severity Index (PASI 75). Ustekinumab is a new human monoclonal antibody with a novel mechanism of action that targets the cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23), naturally occurring proteins that are important in the body's regulation of immune responses and that are also believed to play a role in immune-mediated inflammatory disorders, including psoriasis.
In December 2007, Centocor announced that a Biologics License Application (BLA) had been submitted to the U.S. Food and Drug Administration (FDA) and Janssen-Cilag International NV announced its submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA).
"These findings show that ustekinumab may control plaque psoriasis with as few as four injections a year," says lead study investigator Kenneth Gordon, MD, associate professor, Feinberg School of Medicine, Northwestern University, and Head of Dermatology, Evanston Northwestern Healthcare, Skokie, IL. "We are encouraged by the results seen in clinical trials to date and the hope that ustekinumab may hold for patients and the dermatology community."
The primary endpoint of 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 (PHOENIX 1) study examined the proportion of patients achieving at least a 75 percent improvement from baseline at week 12. Investigators reported findings from PHOENIX 1 that showed at week 12, after two doses, 67 percent of patients receiving 45 mg ustekinumab and 66 percent of patients receiving 90 mg ustekinumab achieved PASI 75 compared with 3 percent of patients receiving placebo (P<0.001 for each comparison versus placebo). Furthermore, 42 percent of patients in the 45 mg ustekinumab dosing group and 37 percent of patients in the 90 mg ustekinumab dosing group achieved PASI 90, or nearly complete clearance of psoriasis, compared with 2 percent of patients receiving placebo (P<0.001). Primary endpoint study findings from PHOENIX 1 were consistent with the week 12 primary endpoint findings reported at the World Congress of Dermatology in October 2007 from another study, 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).
In the PHOENIX 1 study, subjects who received 45 mg or 90 mg of ustekinumab and consistently achieved a 75 percent improvement from baseline were randomized at week 40 to either continue treatment or switch to placebo, with levels of response to maintenance therapy measured at week 52. Of those patients who continued treatment with ustekinumab 45 mg and ustekinumab 90 mg dosing, 87 percent and 91 percent, respectively, had a sustained PASI 75 response compared with 64 percent and 62 percent of patients switched to placebo (P≤0.001 for 45 mg comparison; P<0.001 for 90 mg comparison). Also at week 40, 66 percent and 73 percent of patients achieved PASI 90 after receiving either 45 mg ustekinumab or 90 mg ustekinumab, respectively, and response rates remained stable through week 52 with continued treatment, compared with 37 percent and 38 percent of patients switched to placebo.
"The Phase 3 efficacy and safety data for ustekinumab are extremely promising and offer hope to a patient population in need of additional therapeutic options," says Kim Papp, MD, PhD, Probity Medical Research, Waterloo, Ontario, and lead study investigator.
About the PHOENIX 1 Trial
PHOENIX 1 evaluated the efficacy and safety of ustekinumab in the treatment of 766 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 12 weeks thereafter. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12. Patients responding to ustekinumab through week 40 were randomized to either continue treatment with ustekinumab or were switched to placebo.
Through week 12 (the placebo-controlled portion of the study) the percentages of study participants experiencing at least one adverse event (AE) were comparable between the placebo group (48 percent) and the ustekinumab 45 mg group (57 percent) and 90 mg group (51 percent). Those patients experiencing at least one serious AE were reported as follows: 1 percent and 2 percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, compared with 2 percent of patients receiving placebo. After the randomization at week 40, 46 percent and 49 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, respectively, experienced at least one AE, compared with 56 and 48 percent of patients switched to placebo. Serious AEs were observed in 0 and 1 percent of patients continuing treatment with 45 mg and 90 mg ustekinumab, compared with 0 and 2 percent of patients switched to placebo.
Psoriasis is a chronic, immune-mediated disease, which results from the overproduction of skin cells, resulting in their accumulation on the surface of the skin, which causes red, scaly plaques that may itch and bleed. It is estimated that approximately 7.5 million people in the United States and 10 million Europeans are living with psoriasis and nearly one-quarter of those people have cases that are considered moderate to severe.1
Ustekinumab is a new, 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 regulating the immune system and that are also believed to play a role in immune-mediated inflammatory disorders.
Centocor discovered ustekinumab and has exclusive marketing rights to the product in the United States. Janssen-Cilag companies have exclusive marketing rights in all countries outside of the United States. Centocor, Inc. and the Janssen-Cilag companies are members of the Johnson & Johnson family of companies.
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.
About Janssen-Cilag International NV and Janssen-Cilag
Janssen-Cilag International NV and 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.
1. National Psoriasis Foundation. About Psoriasis: Statistics. Available at: http://www.