Advertisement
"These results demonstrate long-term efficacy of every four week dosingwith golimumab in improving physical symptoms and functional ability as wellas improving quality of life," said Arthur Kavanaugh, M.D., Professor ofMedicine, University of California, San Diego, School of Medicine, and leadstudy investigator. "The sustained effects of golimumab as demonstrated inthese study findings are encouraging for both the physicians treating thiscondition and for the many patients living with this potentially debilitatingdisease."
Advertisement
In the study, Golimumab - A Randomized Evaluation of Safety and Efficacyin Subjects with Psoriatic Arthritis Using a Human Anti-TNF MonoclonalAntibody (GO-REVEAL), 52 percent and 61 percent of patients receivinggolimumab 50 mg and 100 mg, respectively, achieved at least 20 percentimprovement in arthritis signs and symptoms as measured by American College ofRheumatology (ACR 20) response compared with 12 percent of patients receivingplacebo (P < 0.001) at week 24. Through one year, 78 percent of patientscontinuing in the golimumab 50 mg group and 74 percent of patients continuingin the golimumab 100 mg group achieved ACR 20 response. Improvements werealso observed in ACR 50 and ACR 70 measures within the same timeframes.Thirty-two percent and 38 percent of patients receiving golimumab 50 mg and100 mg, respectively, achieved ACR 50 at week 24 compared with 4 percent ofpatients receiving placebo (P < 0.001). Fifty-seven percent and 53 percent ofpatients continuing in the respective golimumab dosing groups achieved ACR 50response through one year. ACR 70 was achieved by 19 percent and 21 percentof patients receiving golimumab 50 mg and 100 mg, respectively, at 24 weekscompared to 1 percent of patients receiving placebo (P < 0.001). Theseresults were sustained through one year with 43 percent of patients receivinggolimumab 50 mg and 31 percent of patients receiving golimumab 100 mgachieving ACR 70.
The majority of patients treated with golimumab every four weeksexperienced improvements in disease activity as measured by good or moderateDisease Activity Score 28 (DAS 28) response. At week 24, 64 percent and 78percent of patients receiving golimumab 50 mg and 100 mg, respectively, wereDAS 28 responders, compared with 24 percent of patients receiving placebo (P <0.001). At one year, 93 percent and 86 percent of patients continuing toreceive golimumab 50 mg and 100 mg, respectively, were DAS 28 responders.
Golimumab-treated patients also experienced substantial and sustainedimprovements in psoriatic skin disease through one year. Patients withgreater than 3 percent Body Surface Area (BSA) psoriasis skin involvement atbaseline were evaluated for Psoriatic Area and Severity Index (PASI)responses. At week 24, 56 percent of patients treated with golimumab 50 mgand 66 percent of patients treated with golimumab 100 mg achieved at least 75percent improvement in PASI (PASI 75), compared with 1.4 percent of patientsreceiving placebo (P < 0.001). At one year, 62 percent and 69 percent ofpatients continuing in the golimumab 50 mg and 100 mg dose groups,respectively, achieved PASI 75.
Improvements in Physical Function and Health-Related Quality of Life
In addition to improvements in signs and symptoms of psoriatic arthritis,patients receiving every four week dosing with golimumab also experiencedclinically meaningful (increase of at least 0.3) improvement in physicalfunction, as measured by the Health Assessment Questionnaire (HAQ). HAQassesses the degree of difficulty a patient has in accomplishing tasks ineight functional areas (dressing, arising, eating, walking, hygiene, reaching,gripping and other activities of daily living.) At week 24, patients treatedwith golimumab 50 mg and 100 mg had a mean improvement of 0.33 and 0.39 score,respectively, as compared to placebo patients worsening by a mean of 0.01score (P < 0.001). At one year, the mean improvements were 0.49 in patientscontinuing to receive golimumab 50 mg and 0.45 in patients continuing toreceive golimumab 100 mg.
"These findings show golimumab to be promising in improving multipleaspects of psoriatic arthritis, including key areas such as physical functionand productivity," said Philip Mease, M.D., Seattle Rheumatology Associates,and Swedish Medical Center, Seattle, and lead study investigator. "Theresults demonstrate that the effectiveness of golimumab extends beyond thecategories of signs and symptoms and improved the lives of patients and thosewho care for them as measured through this analysis."
Patients in both golimumab groups experienced improvements in HRQOL asmeasured by the Physical Component Summary (PCS) and Mental Component Summary(MCS) scores of the Short form (SF)-36 questionnaire. SF-36 assesses well-being in patients along eight domains of health status, including physicalfunctioning, pain, vitality, social functioning, psychological functioning,general health perceptions, and role limitations due to physical and emotionalproblems.
At week 14, patients receiving golimumab 50 mg and 100 mg achieved a meanchange of 6.53 and 7.85 scores, respectively, in PCS compared with a meanchange of 0.63 among patients receiving placebo (P < 0.001). At six months,these results improved to mean changes of 7.42 and 8.22 in the respectivetreatment groups, compared with a mean improvement of 0.67 in the placebogroup (P < 0.001). Also at week 14, patients receiving golimumab 50 mgachieved a mean change of 2.79 in MCS, while patients receiving golimumab 100mg achieved a mean change of 3.56, compared with a mean change of 0.40 inpatients treated with placebo (P < 0.05). At six months, patients receivinggolimumab 50 mg and 100 mg achieved a mean change of 3.37 and 4.29,respectively, compared with 0.60 in placebo-treated patients (P < 0.05).
Self-reported productivity was measured on a Visual Analog Scale (VAS), atool used to assess the patients' daily productivity at work, school or home.Patients receiving golimumab 50 mg and 100 mg experienced improvements inself-reported productivity, both at 16 and 24 weeks, while patients receivingplacebo reported no change in their productivity at 16 weeks and a decrease inproductivity at 24 weeks. Additionally, caregivers of golimumab-treatedpatients experienced a reduction of time lost from work through week 24,compared with caregivers of patients treated with placebo.
Nail, Enthesitis and Dactylitis Response
In patients with nail involvement or enthesitis at baseline, bothgolimumab treatment groups experienced improvements in psoriatic nail changesand enthesitis, as measured by the Nail Psoriasis Severity Index (NAPSI) andthe psoriatic arthritis-modified Maastricht Ankylosing Spondylitis EnthesitisScore (MASES), respectively. In patients with dactylitis at baseline, bothgolimumab dose groups also experienced improvements in dactylitis, though thechanges were not statistically significant with the 50 mg dose. Enthesitis,an inflammation of a tendon, ligament or joint capsule insertion to the bone,and dactylitis, a swelling of digits in the hands or feet, are estimated toaffect more than one-third of people with psoriatic arthritis.
The Biologics License Application (BLA) and Marketing AuthorizationApplication (MAA) for golimumab were submitted earlier in the year and arecurrently under review by the U.S. Food and Drug Administration (FDA) and theEuropean Medicines Agency (EMEA), respectively. The filings are based on theextensive clinical development program for golimumab, including data from fivepivotal Phase 3 trials in rheumatoid arthritis (RA), psoriatic arthritis andankylosing spondylitis.
About the GO-REVEAL Trial
The GO-REVEAL trial involved 405 adults with psoriatic arthritis.Subjects with at least three swollen and tender joints and active psoriaticskin lesions of at least 2 centimeters in diameter were randomly assigned toreceive subcutaneous injections of placebo or golimumab (50 or 100 mg) at week0 and every 4 weeks thereafter through the end of the study. At week 16,patients with inadequate arthritis response were switched to golimumab 50 mg(patients originally receiving placebo) or golimumab 100 mg (patientsoriginally receiving golimumab 50 mg). At week 24 all placebo patientscrossed over to active treatment with golimumab 50 mg. The primary endpointwas ACR 20 response at week 14 for combined golimumab groups and individualgolimumab dose groups versus placebo.
Through week 24, the placebo-controlled portion of the study, 2 percent ofgolimumab-treated patients experienced serious adverse events (SAE) comparedwith 6 percent of patients in the placebo group. Injection site reactions(ISR) occurred in 5 percent of patients receiving golimumab and 3 percent ofpatients receiving placebo. One case of prostate cancer and 2 cases of basalcell carcinoma were reported in golimumab-treated patients. Through week 52,5 percent of golimumab-treated patients experienced SAEs and no tuberculosisor opportunistic infections were reported. Between weeks 24 and 52, one colonand one small cell lung cancer were reported. The small cell lung cancerpatient died; another patient died in a climbing accident. Through one year,golimumab had a similar safety profile to the first 6 months.
Anti-TNF therapies have been associated with serious and sometimes fatalrisks including the risk of tuberculosis and other serious infections,malignancies, heart failure, central nervous system disorders, reactivation ofhepatitis B and other serious events.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic inflammatory arthropathy manifesting withjoint pain and swelling that can lead to joint destruction and debilitation.It is frequently associated with inflamed, scaly, red patches of skinpsoriasis and psoriasis nail involvement. Symptoms may include stiffness andtenderness of the joints and surrounding tissue and reduced range of motion.Joints of the hands, wrists, knees, ankles, feet, lower back and neck arecommonly affected. Psoriasis affects an estimated two to three percent of theworld's population, and approximately one out of three patients affected bypsoriasis may develop psoriatic arthritis. Both men and women are equallyaffected by psoriatic arthritis, most commonly between the ages 30 and 50, inthe peak of their productive years.
About Golimumab
Golimumab, the next-generation human anti-TNF-alpha monoclonal antibodyfrom Centocor Inc. and Schering-Plough Corporation, is currently in the mostcomprehensive Phase 3 development program to date for an anti-TNF-alphabiologic therapy. With ongoing studies for the treatment of rheumatoidarthritis (RA), psoriatic arthritis and ankylosing spondylitis, golimumab isbeing studied as an every four-week subcutaneous injection and an intravenous(IV) infusion therapy. Golimumab targets and neutralizes both the soluble andmembrane-bound forms of TNF-alpha.
Centocor discovered golimumab and has exclusive marketing rights to theproduct in the United States. Schering-Plough has exclusive marketing rightsoutside the United States except in Japan, Indonesia and Taiwan wheregolimumab will be co-marketed by Mitsubishi Tanabe Pharma Corporation andJanssen Pharmaceutical Kabushiki Kaisha; Hong Kong, where golimumab will beexclusively marketed by Janssen-Cilag; and China where golimumab will beexclusively marketed by Xian-Janssen.
About Centocor
Centocor is harnessing the power of world-leading research andbiomanufacturing to deliver innovative biomedicines that transform patients'lives. Centocor has already brought innovation to the treatment of Crohn'sdisease, 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 fromdebilitating immune disorders. Centocor, Inc. is a wholly owned subsidiary ofJohnson & Johnson.
CENTOCOR DISCLOSURE NOTICE: This press release contains "forward-lookingstatements" as defined in the Private Securities Litigation Reform Act of1995. These statements are based on current expectations of future events.If underlying assumptions prove inaccurate or unknown risks or uncertaintiesmaterialize, actual results could vary materially from Centocor's expectationsand projections. Risks and uncertainties include general industry conditionsand competition; economic conditions, such as interest rate and currencyexchange rate fluctuations; technological advances and patents attained bycompetitors; challenges inherent in new product development, includingobtaining regulatory approvals; domestic and foreign health care reforms andgovernmental laws and regulations; and trends toward health care costcontainment. A further list and description of these risks, uncertainties andother factors can be found in Exhibit 99 of Johnson & Johnson's Annual Reporton Form 10-K for the fiscal year ended December 30, 2007. Copies of this Form10-K, as well as subsequent filings, are available online at www.sec.gov,www.jnj.com or on request from Johnson & Johnson. Centocor does not undertaketo update any forward-looking statements as a result of new information orfuture events or developments.
About Schering-Plough
Schering-Plough is a global science-based health care company with leadingprescription, consumer and animal health products. Through internal researchand collaborations with partners, Schering-Plough discovers, develops,manufactures and markets advanced drug therapies to meet important medicalneeds. Schering-Plough's vision is to earn the trust of the physicians,patients and customers served by its approximately 33,500 people around theworld. The company is based in Kenilworth, N.J., and its Web site iswww.schering-plough.com.
SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press releaseincludes certain "forward-looking statements" within the meaning of thePrivate Securities Litigation Reform Act of 1995, including statementsrelating to the potential market for Golimumab. Forward-looking statementsrelate to expectations or forecasts of future events. Schering-Plough doesnot assume the obligation to update any forward-looking statement. Manyfactors could cause actual results to differ materially from Schering-Plough'sforward-looking statements, including market forces, economic factors, productavailability, patent and other intellectual property protection, current andfuture branded, generic or over-the-counter competition, the regulatoryprocess, and any developments following regulatory approval, among otheruncertainties. For further details about these and other factors that mayimpact the forward-looking statements, see Schering-Plough's Securities andExchange Commission filings, including Item 8.01 of Schering-Plough's Form 8-Kfiled October 21, 2008.
SOURCE Centocor
