New Phase 3 Findings Show Stelara Significantly Reduced Signs and Symptoms of Active Psoriatic Arthritis

STELARA® Continued to Provide Benefit in Psoriatic Arthritis Signs and Symptoms through Week 52 in One Phase 3 Trial

TORONTO, November 12, 2012 – Janssen Inc. announced today recent findings from PSUMMIT II, a Phase 3 Janssen-sponsored investigational study that showed patients with active psoriatic arthritis, including those previously treated with one to five tumor necrosis factor (TNF) inhibitors, receiving the interleukin (IL)-12/23 inhibitor STELARA® (ustekinumab) demonstrated significant improvements in signs and symptoms of the disease. Significantly more patients receiving either STELARA® 45 mg or 90 mg achieved at least a 20 per cent improvement in signs and symptoms according to American College of Rheumatology criteria (ACR 20) at week 24, the primary endpoint, than did patients receiving placebo regardless of background methotrexate use. During a late-breaker session of PSUMMIT 1, the initial Phase 3 study, investigators presented 52-week data that showed improvement in efficacy of STELARA® over time in treating signs and symptoms of the disease. These data were presented at the 2012 Annual Meeting of the American College of Rheumatology. Canadian patients accounted for one quarter of the trial participants in the PSUMMIT 1 trial.

“Long-term management of the signs and symptoms of psoriatic arthritis is essential,” said Dr. Darryl Toth, Chief of Dermatology, Windsor Regional and Hotel-Dieu Grace Hospital in Windsor, Ontario and Adjunct Professor, University of Western Ontario. “These new data reveal important new insights into the potential of ustekinumab, a biologic therapy with an alternative mechanism of action, in treating this disease.”

Arthritis is among the leading causes of disability in Canada, affecting more than four million people of every age, physical condition and ethnic background.[i] Psoriatic arthritis is a chronic immune-mediated inflammatory disease characterized by both joint inflammation and the skin lesions associated with psoriasis that affects up to 37 million people worldwide.[ii],[iii] Between 10 and 30 per cent of people with psoriasis will develop psoriatic arthritis.[iv] Though the exact cause of psoriatic arthritis is unknown, genes, the immune system and environmental factors are all believed to play a role in the onset of the disease.

In the Phase 3 Multicenter, Randomized, Double-blind, Placebo?controlled trial of Ustekinumab, a Fully Human anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis Including Those Previously Treated with Biologic Anti-TNF-alpha Agent(s) (PSUMMIT II) study, patients with active psoriatic arthritis despite treatment with disease-modifying antirheumatic drugs (DMARDs), nonsteroidal anti-inflammatory drugs (NSAIDs) and/or anti-TNF-alpha therapy (not intended as a superiority or comparative claim versus TNF inhibitors) were randomized to receive subcutaneous STELARA® 45 mg or 90 mg or placebo at weeks 0, 4 and then every 12 weeks. At week 24, the primary endpoint was met as statistically significantly greater proportions of patients achieving ACR 20 responses (a standard measure of improvement in disease activity) were observed in patients receiving STELARA® 45 mg (43.7 % of patients) or STELARA® 90 mg (43.8 % of patients) compared with 20.2 per cent of patients receiving placebo (P < 0.001 for both comparisons).

Among patients previously treated with TNF inhibitors, 36.7 per cent of patients and 34.5 per cent of patients receiving STELARA® 45 mg or 90 mg, respectively, achieved ACR 20 at week 24 compared with 14.5 per cent of patients receiving placebo (P = 0.006 for STELARA® 45 mg, P = 0.011 for STELARA® 90 mg).

In PSUMMIT II, significantly greater proportions of patients receiving STELARA® 45 or 90 mg achieved ACR 50 at week 24 compared with placebo (17.5 and 22.9 % vs. 6.7 % P = 0.018 for STELARA® 45 mg, P = 0.001 for STELARA® 90 mg). ACR 70 responses for both STELARA® groups were greater, though not significantly, than for the placebo group at week 24. Of patients with at least three per cent body surface involvement of psoriasis at the start of PSUMMIT II, 51.3 per cent and 55.6 per cent of patients receiving STELARA® 45 mg and 90 mg achieved at least a 75 per cent improvement in psoriasis, respectively, as measured by the Psoriasis Area Severity Index (PASI 75), compared with five per cent of patients receiving placebo (P < 0.001 for both comparisons). Significant improvements from baseline to week 24 were also observed in physical function, as measured by the Health Assessment Questionnaire Disability Index (HAQ-DI), in the STELARA® 45 mg and 90 mg treatment groups compared with placebo-treated patients (P = 0.001 for STELARA® 45 mg, P < 0.001 for STELARA® 90 mg).

Similar proportions of patients experienced at least one adverse event (AE) through week 16, the placebo-controlled period, among those receiving STELARA® 45 mg (63.1 %), STELARA® 90 mg (60.6 %) and placebo (54.8 %) with infections being the most common AE. Serious AEs reported among the groups were: STELARA® 45 mg (zero %), STELARA® 90 mg (1.0 %) and placebo (4.8 %). No cases of tuberculosis (TB), opportunistic infections, major adverse cardiovascular events (MACE) or deaths occurred. Through week 24, one serious infection due to complications of pre-existent interstitial lung disease was reported in the placebo group and one skin malignancy (squamous cell carcinoma in situ) occurred in the STELARA® 90 mg group.

Improvement of Signs and Symptoms by STELARA® in Patients with Active Psoriatic Arthritis: Week 52 Results of the Phase 3, Multicenter, Double-blind, Placebo-controlled PSUMMIT I Study

Findings from the Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled trial of Ustekinumab, a Fully Human anti-IL-12/23p40 Monoclonal Antibody, Administered Subcutaneously, in Subjects with Active Psoriatic Arthritis (PSUMMIT I) study are the focus of a late breaker oral presentation. PSUMMIT I is evaluating the efficacy and safety of STELARA® in patients with active psoriatic arthritis despite treatment with conventional therapy (anti-TNF-alpha naïve) through 108 weeks. Patients were randomized to receive subcutaneous STELARA® 45 mg or 90 mg or placebo at weeks 0, 4 and then every 12 weeks. At week 24, 42.4 per cent and 49.5 per cent of patients receiving STELARA® 45 mg and 90 mg, respectively, achieved ACR 20, the primary endpoint, compared with 22.8 per cent of patients receiving placebo (P < 0.001 for both comparisons). Patients who qualified for early escape at week 16 were considered non-responders for the primary and major secondary analyses at week 24. Following week 24 assessment, patients receiving STELARA® 45 mg and 90 mg continued to receive every-12-week maintenance therapy, and placebo patients were crossed over to receive STELARA® 45 mg induction (at weeks 24 and 28) and maintenance therapy every 12 weeks thereafter. Observed data showed that signs and symptoms continued to increase between weeks 24 and week 52, with 55.7 per cent, 60.3 per cent and 65.2 per cent of patients in the STELARA® 45 mg, STELARA® 90 mg and placebo crossover groups, respectively, demonstrating ACR 20 response.

ACR 50 and ACR 70 response rates increased from week 24 through week 52 among patients receiving STELARA® maintenance therapy. At week 24, among patients receiving STELARA® 45 mg, 24.9 per cent achieved ACR 50 compared with 8.7 per cent in the placebo group (P < 0.001), which increased to 31.4 per cent at week 52, and 12.2 per cent achieved ACR 70 compared with 2.3 per cent in the placebo group (P < 0.001) at week 24, which increased to 18 per cent at week 52. Similar changes were observed in the STELARA® 90 mg group at week 24 as 27.9 per cent achieved ACR 50 compared with 8.7 per cent in the placebo group (P < 0.001), which increased to 37 per cent at week 52, and 14.2 per cent achieved ACR 70 compared with 2.3 per cent in the placebo group (P < 0.001) at week 24, which increased to 21.2 per cent at week 52. Investigators also reported continued improvements in physical function and skin symptoms through the end of the study, with nearly half of patients demonstrating clinically meaningful change from baseline in HAQ-DI scores, and more than two-thirds of patients achieving PASI 75 at week 52.

Among study participants affected with enthesitis (inflammation of the entheses, the sites where tendons or ligaments attach to bone, n=425) or dactylitis (inflammation of the finger or toe, n=286) at baseline, patients receiving STELARA® achieved clinically relevant improvements in both measures at week 24 and week 52. At week 24, median per cent changes in enthesitis scores (-42.9 for STELARA® 45 mg and -50.0 for STELARA® 90 mg) and dactylitis scores (-75.0 for STELARA® 45 mg and -70.8 for STELARA® 90 mg) were significantly higher than those seen for patients receiving placebo (P < 0.001 for all comparisons). Improvements in enthesitis scores (-83.3, -74.2 and -87.5) and dactylitis scores (-100 in all patients) in the STELARA® 45 mg, 90 mg and crossover groups, respectively, continued through week 52.

A similar proportion of patients experienced at least one AE or serious AE through week 16, the placebo-controlled period of PSUMMIT I. Safety through week 52 was consistent with that observed during the placebo-controlled period between STELARA® 45 mg and 90 mg groups in the incidence of AEs (66.8 % and 64.7 %, respectively) and serious AEs (5.9 % and 3.4 %, respectively). No malignancies, cases of TB, opportunistic infections or deaths occurred through week 52. Investigators reported three MACE in STELARA®-treated patients in patients with multiple pre-existing cardiovascular risk factors.

About PSUMMIT II
The PSUMMIT II trial is a Phase 3, multicenter, randomized, double-blind, placebo?controlled study including 312 adults with psoriatic arthritis designed to evaluate the efficacy and safety of STELARA® in adults with psoriatic arthritis. The trial included patients diagnosed with active psoriatic arthritis who had at least five tender and five swollen joints and C-reactive protein (CRP) levels of at least 0.3 mg/dL despite treatment with DMARDs and/or NSAIDs and/or prior exposure to anti-TNF treatment, including 8 to 14 weeks of exposure to currently available anti-TNF-alpha treatments and/or documented evidence of anti-TNF-alpha intolerance/toxicity with 8 to 14 weeks exposure. Concurrent methotrexate use was permitted but not mandated. Within the trial, 180 patients had prior exposure to anti-TNF-alpha treatments and 132 patients were anti-TNF-alpha naïve.

Patients were randomized to three groups: STELARA® 45 mg or STELARA® 90 mg at weeks 0, 4, and then every 12 weeks or placebo. At week 16, patients with less than a five per cent improvement in tender and swollen joint counts were entered into blinded early escape to receive STELARA® 45 mg (patients receiving placebo) or STELARA® 90 mg (patients receiving STELARA® 45 mg). The primary endpoint was ACR 20 response at week 24. Secondary endpoints at week 24 included ACR 50 and ACR 70 response, Disease Activity Score (DAS) 28 using CRP (DAS28-CRP) response, PASI 75 in patients with at least three per cent body surface area involvement at baseline, improvements in enthesitis and dactylitis scores and improvements in HAQ-DI scores.

About PSUMMIT I
The PSUMMIT I trial is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study including 615 adults with psoriatic arthritis designed to evaluate the efficacy and safety of STELARA® in adults with psoriatic arthritis. The trial included patients diagnosed with active psoriatic arthritis who had at least five tender and five swollen joints and CRP levels of at least 0.3 mg/dL despite treatment with DMARDs and/or NSAIDs. Patients were naïve to treatment with anti-TNF-alpha therapies and/or IL-12/23 inhibitors.

Patients were randomized to three groups: STELARA® 45 mg or STELARA® 90 mg at weeks 0, 4 and then every 12 weeks or placebo. At week 16, patients with less than a five per cent improvement in tender and swollen joint counts were entered into blinded early escape to receive STELARA® 45 mg (patients receiving placebo) or STELARA® 90 mg (patients receiving STELARA® 45 mg). The primary endpoint was ACR 20 response at week 24. Secondary endpoints at week 24 included ACR 50 and ACR 70 response, DAS28-CRP response, PASI 75 in patients with at least three per cent body surface area involvement at baseline, improvements in enthesitis and dactylitis scores and improvements in HAQ-DI scores. Safety and efficacy results were reported through week 52 in the trial. Initial week 24 results were presented earlier this year at the 2012 EULAR Annual Congress.

About STELARA®
STELARA® is a 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.

STELARA® works by targeting and regulating the activity of cytokines interleukin-12 (IL-12) and interleukin-23 (IL-23). 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.

Janssen Biotech, Inc. discovered and developed STELARA® and has exclusive marketing rights to the product in the United States. Janssen companies, including Janssen Inc. in Canada, have exclusive marketing rights to STELARA® worldwide.

STELARA® is currently approved for the treatment of moderate to severe plaque psoriasis in 69 countries including Canada. STELARA® is under investigation in Phase 3 development programs for the treatment of active psoriatic arthritis and moderate to severe Crohn’s disease.

For more information about STELARA®, visit Janssen.ca or Health Canada at http://www.hc-sc.gc.ca/dhp-mps/prodpharma/sbd-smd/drug-med/sbd_smd_2009_stelara_114272-eng.php#a1.

STELARA® 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® (ustekinumab) is a selective immunomodulator. Immunomodulating agents have the potential to increase the risk of malignancy. 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. STELARA® is contraindicated in patients with known hypersensitivity to STELARA® or any of its components and for patients with severe infections such as sepsis, tuberculosis and opportunistic 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.

The full product monograph for STELARA® can be accessed at the following link: http://www.janssen.ca/product/190.

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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For more information, or to arrange an interview, please contact:

Lisa Cancian
lisa.cancian@gcicanada.com<mailto:marsha.rosenberg@edelman.com>
(416) 486-5906

Kate Hanna
Janssen Inc.
Khanna7@its.jnj.com<mailto:Khanna7@its.jnj.com>
(416) 382-5017

References:

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[i] The Arthritis Society. Psoriatic Arthritis Know Your Options. Available at: http://www.arthritis.ca/document.doc?id=335. Last accessed: November 7, 2012.

[ii] About Psoriasis: Statistics. National Psoriasis Foundation. Available at: http://www.psoriasis.org/learn_statistics. Last accessed: November 7, 2012.

[iii] About Psoriatic Arthritis. National Psoriasis Foundation. Available at: http://psoriasis.org/psoriatic-arthritis. Last accessed: November 7, 2012.

[iv] The Arthritis Society. Psoriatic Arthritis Know Your Options. Available at: http://www.arthritis.ca/document.doc?id=335. Last accessed: November 7, 2012.
 

Posted: November 2012

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