Landmark Study Shows Ustekinumab Demonstrated Superior Efficacy to Enbrel (Etanercept) for Moderate to Severe Plaque Psoriasis

A Greater Proportion of Patients Receiving Ustekinumab Delivered in Two Subcutaneous Doses Achieved Significant Skin Clearance at the Primary Endpoint Compared with Patients Receiving Enbrel Delivered in 24 Subcutaneous Doses

HORSHAM, Pa., September 18, 2008 /PRNewswire/ -- New findings from a Phase 3 multicenter, randomized head-to-head study comparing ustekinumab and Enbrel(R) (etanercept) for the treatment of moderate to severe psoriasis showed ustekinumab superior to Enbrel according to primary and major secondary efficacy endpoints. The primary endpoint of the trial was the percentage of participants achieving at least a 75 percent reduction in psoriasis at week 12 as measured by the Psoriasis Area and Severity Index (PASI 75). At week 12, after two subcutaneous injections at weeks 0 and 4, 68 percent and 74 percent of patients receiving ustekinumab 45 mg or ustekinumab 90 mg, respectively, achieved a PASI 75 compared with 57 percent of patients receiving Enbrel 50 mg subcutaneous injections twice weekly for twelve weeks (P = 0.012 for ustekinumab 45 mg; P < 0.001 for ustekinumab 90 mg, each compared with Enbrel). Investigators presented these data today at the 17th meeting of the European Academy of Dermatology and Venereology (EADV) in Paris, France.

Ustekinumab is a new, investigational 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 believed to play a role in immune-mediated inflammatory disorders, including psoriasis.

"These findings reinforce the promise of ustekinumab as an infrequently administered and highly effective biologic therapy for the treatment of adults with moderate to severe psoriasis," said Bruce Strober, MD, PhD, Department of Dermatology, School of Medicine, New York, New York, United States, and trial investigator. "Currently available biologic therapies have greatly improved the treatment of psoriasis, yet unmet needs in treatment remain for patients living with this chronic inflammatory disease."

Investigators also reported that patients receiving ustekinumab achieved higher marked improvements in psoriasis as assessed by PASI 90 improvement, or nearly complete clearance of psoriasis, and Physician Global Assessment (PGA) scores compared with patients receiving Enbrel, which were major secondary endpoints of the trial. At week 12, 36 percent of patients receiving ustekinumab 45 mg and 45 percent of patients receiving ustekinumab 90 mg achieved PASI 90 compared with 23 percent of patients receiving Enbrel (P < 0.001 for each comparison versus Enbrel). Moreover, a greater proportion of patients in the ustekinumab 45 mg and 90 mg treatment groups achieved a PGA score of "cleared" or "minimal" (65 percent and 71 percent, respectively) compared with patients in the Enbrel treatment group (49 percent) (P < 0.001 for each comparison versus Enbrel).

Through week 12, the comparator-controlled portion of the study, the percentages of study participants experiencing at least one adverse event (AE) were comparable between the ustekinumab 45 mg group (66 percent), the ustekinumab 90 mg group (68 percent) and the Enbrel 50 mg group (69 percent). Those patients experiencing at least one serious AE were reported as follows: 1.9 percent and 1.2 percent of patients receiving 45 mg or 90 mg ustekinumab, respectively, compared with 1.2 percent of patients receiving Enbrel. AEs leading to treatment discontinuation occurred in 1.9 percent and 1.2 percent of patients in the ustekinumab 45 mg and ustekinumab 90mg groups, respectively, compared with 2.3 percent of patients treated with Enbrel. Rates of specific adverse events were generally comparable between treatment groups with the exception of injection site erythema which was reported in 14.7 percent of subjects treated with Enbrel versus 0.7 percent of subjects in the combined ustekinumab groups, though this disparity may have been influenced by the greater number of Enbrel injections required (up to 48 in the 12-week study) compared with two ustekinumab injections.

"This study is significant for the dermatology community as it is the first comparator trial of biologic therapies for psoriasis," said Christopher Griffiths, MD, FRCP, School of Medicine, University of Manchester, Manchester, UK, and lead trial investigator. "Treatment with ustekinumab, which has a new mechanism of action that targets interleukins 12 and 23, has demonstrated significant clinical efficacy with infrequent self-administered injections. Both are important considerations when evaluating the burden of disease for many adult patients living with moderate to severe psoriasis and who are candidates for a biologic treatment."

About the ACCEPT Trial

The Phase 3, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Ustekinumab Compared to Etanercept in the Treatment of Subjects with Moderate to Severe Plaque Psoriasis (ACCEPT) included 903 patients with chronic plaque psoriasis (etanercept=347, ustekinumab 45 mg=209, ustekinumab 90 mg=347). Patients were randomized to receive subcutaneously administered ustekinumab or etanercept. Patients randomized to receive ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4. Patients in the etanercept group received twice-weekly doses of 50 mg for 12 weeks. The primary endpoint of the study was the proportion of patients who achieved PASI 75 at week 12.

About Psoriasis

Psoriasis is a chronic, immune-mediated disease that 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.

About Ustekinumab

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 believed to play a role in immune-mediated inflammatory disorders.

On June 17, 2008, the FDA's Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) unanimously recommended ustekinumab for approval. DODAC is convened on request of the FDA to review and evaluate safety and efficacy data of human drug products for use in the treatment of dermatologic and ophthalmologic conditions. The committee provides non-binding recommendations based on its evaluation; however, the FDA makes the final decision on approval of the drug. Ustekinumab is also under review by the European Medicines Agency (EMEA).

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.

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

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.

Enbrel is a registered trademark of Amgen and Wyeth Pharmaceuticals.

CONTACT: Media contact: Brian Kenney of Centocor, Inc., +1-215-325-2107,mobile: +1-215-620-0111; Investor contacts: Louise Mehrotra,+1-732-524-6491, or Tina Pinto, +1-732-524-2034, both of Johnson & Johnson

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Posted: September 2008

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