TORONTO, May 25, 2011 - New findings presented today from pooled analyses of the STELARA™ (ustekinumab) psoriasis clinical development program showed that the safety profile of STELARA™ and rates of adverse events remained consistent and stable over time in adults with moderate to severe plaque psoriasis receiving up to four years of treatment. Investigators also reported findings from an analysis of four placebo-controlled Phase 3 trials across patient populations on three continents and found that the efficacy and safety of STELARA™ in patients of Japanese and Korean-Taiwanese descent were consistent with findings previously reported in North American and European populations. Both sets of data were presented at the 22nd World Congress of Dermatology in Seoul, Korea.
Psoriasis, a chronic, immune-mediated disease that results from the overproduction of skin cells, affects one million Canadians,1 and 125 million people worldwide. Plaque psoriasis often results in patches of thick, red or inflamed skin covered with silvery scales known as plaques. These plaques usually itch or feel sore, can crack and bleed, and can occur anywhere on the body. The disease symptoms can range from mild, to moderate, to severe and disabling. STELARA™ is currently approved in 57 countries for the treatment of moderate to severe plaque psoriasis.
"These findings are promising and support a favorable benefit-to-risk profile for STELARA™ with up to four years of treatment," said Kristian Reich, MD, Department of Dermatology of Dermatolgikum, Hamburg, Germany, and lead trial investigator for the PHOENIX 2 study. "Ongoing studies in psoriasis and psoriatic arthritis will continue to define the safety profile of STELARA™ in the psoriatic population." Use of STELARA™ in psoriatic arthritis is for investigational purposes only. STELARA™ is not approved for psoriatic arthritis in Canada.
Pooled safety data from a total of 3,117 patients who participated in a Phase 2 STELARA™ trial and the Phase 3 PHOENIX 1, PHOENIX 2 and ACCEPT studies showed rates of adverse events (AEs) to be generally stable over time through up to four years of treatment with STELARA™, with the most commonly reported AEs [greater than 5 per 100 patient years (PY)] including nasopharyngitis, upper respiratory tract infection, arthralgia, sinusitis, headache and back pain and influenza. Observed occurrences of AEs of interest, including serious infections (0.8 and 1.32 for 45 mg and 90 mg STELARA™ patient groups, respectively, per 100 PY), non-melanoma skin cancer (0.70; 0.53 per 100 PY, respectively), other malignancies (0.63; 0.61 per 100 PY, respectively) and major adverse cardiovascular events (MACE) (0.42; 0.36 per 100 PY, respectively) remained generally stable during the time periods evaluated. The observed rate of malignancies (excluding non-melanoma skin cancers) was consistent with that expected in the general U.S. population, derived from the Surveillance, Epidemiology and End Results (SEER) Database. Rate of non-fatal myocardial infarction (MI) or stroke was consistent with or lower than that expected in the general U.S. population and psoriasis populations, derived from the Framingham Database and General Practice Research Database (GPRD), respectively.
The four year safety analysis of the Phase 2, PHOENIX 1, PHOENIX 2 and ACCEPT trials evaluated the largest psoriasis-focused clinical trial safety database for a biologic reported to date, with more than 1,100 patients who have had at least three years of treatment with STELARA™ and more than 600 patients treated for four or more years for a total of nearly 6,800 PY.
Consistency of Responses across Different Ethnic Populations with Moderate-to-Severe Plaque Psoriasis: Results from the STELARA Psoriasis Clinical Development Program
Additional findings from a separate analysis found STELARA™ efficacy and safety across Asian populations with moderate to severe plaque psoriasis to be consistent with those observed in North American and European populations, according to data from PHOENIX 1 (n=766) and PHOENIX 2 (n=1230) compared with Japanese and Korean-Taiwanese populations evaluated in the JPN-02 (n=158) and PEARL (n=121) trials, respectively.
"Psoriasis is an auto-inflammatory disease that affects millions of people worldwide and all ethnic backgrounds," said Dr. Kim Papp, dermatologist, and study investigator. "These data show the consistency of response with STELARA™ in the treatment of psoriasis across ethnic populations. These data highlight the safety of STELARA™ for people with chronic moderate to severe plaque psoriasis. And, these findings are important considerations for the dermatology community as well as our patients."
In the four analyzed studies, patients received subcutaneous injections of STELARA™ 45 mg or 90 mg, or placebo at weeks 0 and 4, although only the STELARA™ 45 mg dose was evaluated in the PEARL trial. STELARA™ patients received a third dose at week 16, while placebo-treated patients crossed over to receive active treatment at weeks 12 and 16. At week 12, the primary endpoint, a 75 per cent improvement as measured by the Psoriasis Area Severity Index (PASI 75), was achieved by a significantly greater proportion of patients across all studies when compared with the placebo group (P > 0.001). Among patients receiving STELARA™ 45 mg, 66.9 per cent, 59.4 per cent and 67.2 per cent achieved PASI 75 in the North American/European, Japanese and Korean-Taiwanese patient populations, respectively. In patients receiving 90 mg, 72.1 per cent and 67.7 per cent of patients achieved PASI 75 in the North American/European and Japanese populations. Placebo rates of response were 3.5 per cent, 6.5 per cent and 5.0 per cent in the PHOENIX 1 & 2, Japanese and PEARL trials, respectively. These responses continued to improve through week 28 across groups, with similar responses seen in placebo-treated patients following crossover to treatment with STELARA™. STELARA™-treated patients also demonstrated clinically meaningful improvements in quality of life, as measured by the Dermatology Life Quality Index (DLQI), at weeks 12 and 28 across the four trials.
Rates of AEs and serious AEs through week 12 were comparable overall between STELARA™ and placebo groups in the North American/European, Japanese and Korean-Taiwanese trials. Among patients receiving STELARA™ 45 mg (or 90 mg), 54.8 (49.7) per cent, 65.6 (59.7) per cent and 65.6 per cent of patients across patient populations reported at least one AE, compared with 49.2 per cent, 65.6 per cent and 70.0 per cent of placebo patients, respectively. Similar safety results were seen through week 28 of each trial. Please read the Important Safety Information for STELARA™ below.
About the Phase 2 Study
The 36-week, double-blind, placebo-controlled trial, evaluated 320 patients with plaque psoriasis who were randomized to receive one of four dose regimens of STELARA™ (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 STELARA™, 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 STELARA™ at week 20. Safety data was collected through week 52 of the study.
About the PHOENIX 1 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 (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 STELARA™ or placebo. Patients randomized to receive STELARA™ 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 STELARA™ at weeks 12 and 16 and every 12 weeks thereafter. Some patients inadequately responding to STELARA™ at weeks 28 and 40 were eligible to switch to every 8 week dosing. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12. Patients responding to STELARA™ through week 40 were randomized to continue treatment with STELARA or were switched to placebo with potential retreatment after loss of response. The long-term extension of this trial is ongoing and is expected to be completed in June 2011; PHOENIX 1 will provide up to 5 years of safety and efficacy data.
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) evaluated the efficacy and safety of STELARA™ in 1,230 patients with moderate to severe plaque psoriasis. At baseline, patients were randomized to receive STELARA™ 45 mg or 90 mg at weeks 0, 4 and every 12 weeks thereafter, or placebo at weeks 0 and 4. Patients initially randomized to placebo at baseline were assigned to cross over to either STELARA™ 45 mg or 90 mg at weeks 12, 16 and every 12 weeks thereafter. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12. Patients partially responding to STELARA™ at Week 28 were randomized to continue treatment with STELARA™ every 12 weeks or were switched to every 8 week dosing. Patients inadequately responding to STELARA at week 40 and during the long-term extension were eligible to switch to every 8 week dosing. Patients inadequately responding to STELARA™ 45 mg every 8 weeks during the long-term extension were eligible to switch to 90 mg dosing. For patients who underwent dose-escalation from STELARA™ 45 mg to 90 mg, pooled safety results were based on the dose received at the time an adverse event occurred. The long-term extension of this trial is ongoing and is expected to be completed in November 2011; PHOENIX 2 will provide up to five years of safety and efficacy data.
About the ACCEPT Trial
The Phase 3, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Ustekinumab Compared to Etanercept (Enbrel®) in the Treatment of Subjects with Moderate to Severe Plaque Psoriasis (ACCEPT) included 903 patients with chronic plaque psoriasis (etanercept=347, STELARA™ 45 mg=209, STELARA 90 mg=347). Patients were randomized to receive subcutaneously administered STELARA™ or etanercept. Patients randomized to receive STELARA™ 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. At week 12, patients in the etanercept group who were classified as non-responders (i.e., had moderate, marked or severe psoriasis) received 90 mg of STELARA™ at weeks 16 and 20. STELARA™ non-responders received one additional dose of STELARA™ at week 16. Treatment was interrupted for all patients who had cleared, minimal or mild psoriasis at the end of week 12, and all patients were retreated with 45 or 90 mg STELARA when their disease worsened to moderate or worse.
About the PEARL Trial
PEARL was a Phase 3, multicenter, randomized study of subcutaneous injections of placebo and STELARA™ 45 mg for the treatment of moderate to severe plaque psoriasis in Korean and Taiwanese patients. Those patients who were randomized to STELARA™ received 45 mg doses at weeks 0, 4 and 16, and a placebo injection at week 12 to maintain the blind. Patients randomized to receive placebo at weeks 0 and 4 crossed over to receive STELARA™ 45 mg at weeks 12 and 16. All patients were followed through week 36. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12.
About the Japanese (JPN02) Trial
JPN-02 was a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study to evaluate the efficacy and safety of STELARA™ in Japanese patients with moderate to severe plaque-type psoriasis. STELARA™ was to be administered at either 45 mg or 90 mg subcutaneous at weeks 0 and 4 and then once every 12 weeks through week 52; or placebo at weeks 0 and 4 and crossover to receive either 45 mg or 90 mg STELARA™ at weeks 12 and 16 and then once every 12 weeks through week 52. The primary endpoint of the study was the proportion of patients achieving PASI 75 at week 12.
STELARA™ was awarded the 2010 Prix Galien Canada Innovative Product Award. The Prix Galien is the most prestigious award in the field of Canadian pharmaceutical research and innovation. Referred to as the Nobel Prize of pharmaceutical research, it recognizes the efforts and achievements of pharmaceutical research and development.
STELARA™ is a first-in-class, human, monoclonal antibody approved first in the world by Health Canada in December 2008 for the treatment of psoriasis. A selective immunomodulating agent, STELARA™ is indicated for the treatment of adult patients with chronic moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy.2
STELARA™ works by targeting and regulating the activity of cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23).3 These cytokines are naturally occurring proteins that are important in regulating immune responses, and are thought to be associated with immune-mediated inflammatory disorders, including plaque psoriasis.4
Centocor Ortho Biotech Inc. discovered and developed STELARA™ and has exclusive marketing rights to the product in the United States. Janssen Inc. has exclusive marketing rights in Canada for the treatment of chronic moderate to severe plaque psoriasis.
Important Safety Information
STELARA™ is a prescription medicine that affects the immune system. The most common adverse reactions (greater than 10 per cent) in controlled and uncontrolled portions of the psoriasis clinical studies with STELARA™ were nasopharyngitis and upper respiratory tract infection. Most were considered to be mild and did not necessitate drug discontinuation.
STELARA™ has not been studied in patients with a history of malignancy. Caution should be exercised when considering the use of STELARA™ in patients with a history of malignancy or when considering continuing treatment in patients who develop a malignancy.
STELARA™ is a selective immunomodulator and may have the potential to increase the risk of infections and reactivate latent infections. Caution should be exercised when considering the use of STELARA™ in patients with a chronic infection or a history of recurrent infection. If a patient develops a serious infection, they should be closely monitored and STELARA™ should not be administered until the infection resolves.
Prior to initiating treatment with STELARA™, patients should be evaluated for tuberculosis infection. STELARA™ should not be given to patients with active tuberculosis.
About Janssen Inc.
As a member of the Janssen Pharmaceutical Companies, Janssen Inc. is dedicated to addressing and solving the most important unmet medical needs in pain management, psychiatry, oncology, immunology, psoriasis, virology, anemia, attention deficit hyperactivity disorder, gastroenterology and women's health. Driven by our commitment to the passionate pursuit of science for the benefit of patients, we work together to bring innovative ideas, products and services to patients around the world.
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