WASHINGTON, D.C., Nov. 15, 2016 ― Janssen Research & Development, LLC (Janssen) announced today positive efficacy and safety results from a Phase 2 study investigating guselkumab, an anti-interleukin (IL)-23 monoclonal antibody administered by subcutaneous injection, for the treatment of active psoriatic arthritis. According to findings presented at the 2016 ACR/ARHP Annual Meeting, 58 percent of patients receiving guselkumab achieved at least a 20 percent improvement in signs and symptoms of disease (ACR 20) at week 24, the study’s primary endpoint, compared with 18.4 percent of patients receiving placebo (P < 0.001). Data from the trial also showed statistically significant improvements in all secondary endpoints including physical function, psoriatic skin lesions and other health related outcomes, compared with patients receiving placebo. The guselkumab Phase 2 results in active psoriatic arthritis follow positive Phase 3 study results in moderate to severe plaque psoriasis recently presented at the European Academy of Dermatology and Venereology Congress in Vienna.
“Guselkumab is the first biologic therapy targeting IL-23 specifically, and the Phase 2 results are promising as they demonstrate a significant improvement in the treatment of active psoriatic arthritis,” said Atul Deodhar, M.D., MRCP, FACP, FACR, Professor of Medicine, Oregon Health & Science University and lead study author.* “It’s encouraging to see how well patients responded to guselkumab in this study with respect to improvements in disease signs and symptoms, as early as week four, and in other health-related quality of life outcomes, including measures of physical and mental health.”
In addition to meeting the primary endpoint of the study, all secondary endpoints achieved statistical significance in comparisons between the guselkumab and placebo groups. Secondary endpoints included ACR20 response at 16 weeks, ACR50 response at 24 weeks, the proportion of patients with 75 percent or greater improvement from baseline in psoriatic skin lesions as measured by the Psoriasis Area Severity Index
(PASI 75) at 24 weeks, change from baseline in the health assessment questionnaire disability index (HAQ-DI) at 24 weeks, change in baseline measures of physical and mental health reported by patients through the Medical Outcomes Study Short Form-36 questionnaire (SF-36), percent change from baseline in Leeds Enthesitis Index (LEI) at 24 weeks, percent change from baseline in dactylitis score at 24 weeks, and proportion of patients achieving Minimal Disease Activity (MDA) at 24 weeks.
· ACR20 response was achieved by 60 percent of patients receiving guselkumab compared with 16.3 percent of patients receiving placebo (P < 0.001) at week 16.
· ACR50 response was achieved by 34 percent of patients receiving guselkumab compared with 10.2 percent of patients receiving placebo (P = 0.002) at week 24.
· PASI 75 response was achieved by 78.6 percent of patients receiving guselkumab compared with 12.5 percent of patients receiving placebo (P < 0.001) at week 24.
· Mean improvements in HAQ-DI scores were 0.43 for the guselkumab group compared with 0.06 for the placebo group (P < 0.001) at week 24.
Patients treated with guselkumab had significantly greater improvements in enthesitis (inflammation of the entheses, the sites at which tendons or ligaments attach to bone) and dactylitis (inflammation of the fingers or toes), and in health-related quality of life as measured by SF-36 physical component summary (SF36-PCS) scores and mental component summary (SF36-MCS) scores compared with patients treated with placebo at week 24. In addition, a greater percentage of patients in the guselkumab group achieved MDA compared with the placebo group at week 24 (23 percent versus 2 percent, respectively, [P = 0.001]). MDA for psoriatic arthritis is a composite measure encompassing clinically important aspects of the disease, including arthritis, psoriasis, enthesitis, pain, patient-assessed global disease activity, and physical function.
Safety observations through week 24 showed that 36.0 percent versus 32.7 percent experienced adverse events (AEs), in the guselkumab and placebo groups, respectively. The most common AEs were infections. Two serious AEs were reported including one knee injury and one myocardial infarction. Investigators remain blinded to individual treatment group assignments, as the study is ongoing. There were no serious infections, malignancies, or deaths through week 24.
“The efficacy and safety results from this Phase 2 study show the potential of guselkumab in the treatment of active psoriatic arthritis,” said Newman Yielding, M.D., Head of Immunology Development, Janssen. “We plan to advance guselkumab into a Phase 3 psoriatic arthritis development program next year to further characterize this novel monoclonal antibody’s profile in the treatment of this complex inflammatory disease.”
About the Phase 2 Guselkumab Psoriatic Arthritis Trial
The Phase 2, randomized, double-blind, placebo–controlled, multicenter trial was designed to evaluate the efficacy and safety of guselkumab compared with placebo in adult patients with active psoriatic arthritis and a body surface area (BSA) of plaque psoriasis greater than or equal to three percent, despite current or previous treatment with standard-of-care therapies, including those previously exposed to anti-tumor necrosis factor (TNF)-alpha agents. Patients (n=149) were randomized in a two-to-one ratio to receive guselkumab 100 mg or placebo by subcutaneous injection at weeks 0, 4 and then every 8 weeks thereafter, followed by a 20-week active treatment period. At week 16, patients from either group with less than five percent improvement from baseline in both swollen and tender joint counts were eligible for early escape to open-label ustekinumab. At week 24, all remaining placebo patients crossed over to receive guselkumab 100 mg, which was administered again at week 28, and then every 8 weeks thereafter through week 44.
Guselkumab is a human monoclonal antibody with a novel mechanism of action that targets the protein interleukin (IL)-23 and is in Phase 3 development as a subcutaneously administered therapy for the treatment of moderate to severe plaque psoriasis.
About Psoriatic Arthritis
Psoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease characterized by both joint inflammation and the skin lesions associated with psoriasis which effects 125 million people worldwide.1 An estimated 600,000 Americans—and more than 12 million people worldwide—have PsA.2 While estimates of the prevalence of psoriatic arthritis among people living with psoriasis vary, up to 30 percent may develop inflammatory arthritis.3 The disease causes pain, stiffness and swelling in and around the joints and commonly appears between the ages of 30 and 50, but can develop at any time.4 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.4
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us on Twitter at https://twitter.com/JanssenGlobal.
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995, regarding plans for continued development of guselkumab. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC and Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; competition, including technological advances, new products and patents attained by competitors; challenges to patents; manufacturing difficulties or delays; product efficacy or safety concerns resulting in product recalls or regulatory action; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither Janssen Research & Development, LLC nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
*Compensated as a steering committee member.
1. World Psoriasis Day. Available at: http://www.worldpsoriasisday.com/web/page.aspx?sid=8538. Accessed October 2016.
2. Spondylitis Association of America. Living with Psoriatic Arthritis (PsA): An Overview of PsA: Available at http://www.spondylitis.org/About-Spondylitis/Psoriatic-Arthritis. Accessed October 2016.
3. World Health Organization. The Global Burden of Disease: 2004 Update. p32. Available at: http://www.who.int/healthinfo/global_burden_disease/GBD_report_2004update_full.pdf. Accessed October 2016.
4. National Psoriasis Foundation. About Psoriatic Arthritis. Available at: http://www.psoriasis.org/psoriatic-arthritis. Accessed October 2016.
Joseph J. Wolk
Johnson & Johnson
Johnson & Johnson