Cimzia® (certolizumab pegol) shows sustained clinical improvements over three years and inhibition of joint progression in patients with rheumatoid arthritis
In adult patients with moderate to severely active rheumatoid arthritis, Cimzia® provided rapid and sustained improvements in ACR responses, DAS 28 scores, HAQ-DI scores and in pain VAS over three years[1]

Sustained inhibition of progression of structural joint damage was observed in patients treated with Cimzia® up to 2.5 years[1]

ROME June 16th, 2010, 08.30 CET - UCB today announced data showing that rapid improvements in ACR20, physical function, pain and fatigue of rheumatoid arthritis (RA) as early as Week 1, following treatment with Cimzia® (certolizumab pegol), together with methotrexate (MTX), was sustained up to 148 weeks.[1] Inhibition of progression of structural joint damage (seen at Week 24) was sustained up to the last x-ray evaluation at 2.5 years.[1] Cimzia® was well tolerated with no new safety signals across three years.[1]

"These data have shown certolizumab pegol as an effective and well tolerated therapy in patients treated for a sustained period of time," said lead investigator Josef Smolen, M.D., and Chairman of the Department of Rheumatology, Internal Medicine III, Medical University of Vienna, "As a chronic condition, it is critical patients and physicians are confident that treatments deliver a rapid response and are effective in the longer term to help maintain overall quality of life."

The data presented were from an open label extension (OLE) to the phase III, Rheumatoid Arthritis Prevention of Structural Damage (RAPID 2) study.[1] The OLE was designed to investigate the long-term efficacy and safety of Cimzia® and methotrexate (MTX) over three years (148 weeks).[1] Patients receiving Cimzia® 200mg or 400mg + MTX who completed RAPID 2 initially received Cimzia® 400mg + MTX every other week (EOW) in the OLE; this Cimzia® dose was decreased from 400mg to 200mg EOW per protocol (after ≥6 months in the OLE).[1]*

Efficacy was measured by ACR 20/50/70 responder rates, DAS28[ESR]. Patient-reported outcomes included physical function (assessed using the Health Assessment Questionnaire-Disability Index [HAQ-DI]) and pain (assessed on a 0-100-mm visual analogue scale [VAS]).

At 148 weeks, ACR responses in Cimzia® 200mg completers were sustained.[1] Sixty-three percent of Cimzia® 200mg completers who entered the OLE had an ACR50 response.[1] ACR20/50/70 response rates were similar in CZP 400mg completers.[1] Low disease activity (DAS28[ESR]<3.2) was reported in 39% of patients with 36% of patients originally treated with 200mg Cimzia® and 42% originally treated with 400mg Cimzia®. Twenty percent of patients had remission at week 148[1] (19% of patients originally treated with 200mg Cimzia® and 20% originally treated with 400 mg Cimzia®).[1]

Improvements in HAQ-DI scores were sustained over 3 years in Cimzia® 200mg completers,[1] as were improvements in pain VAS.[1] Results were similar in Cimzia® 400mg completers.[1]

Inhibition of radiographic progression observed during the double-blind phase (weeks 0-24) was sustained up to the last x-ray evaluation at 2.5 years.[1] The mean change from baseline in modified total Sharp score (mTSS) for the combined Cimzia® dose groups at Week 128 was 0.75.[1]

There was no increase in incidence of AEs in the OLE, nor were any new safety signals observed.[1]

In Cimzia®'s pivotal clinical trials reported serious adverse reactions included infections (including tuberculosis) and malignancies (including lymphoma). The most common adverse reactions belonged to the system organ classes Infections and Infestations, reported in 15.5% of patients on Cimzia® and 7.6% of patients on placebo, and General disorders and administration site conditions, reported in 10.0% of patients on Cimzia® and 9.7% of patients on placebo. A pooled analysis of the safety data showed there was a low incidence of injection site pain (1.5%) and a low level of discontinuations due to adverse events (5%). Cimzia® demonstrated a favorable risk-benefit profile in patients with at least up to two years of drug exposure.

These and other Cimzia® data are available on display during the 2010 Annual Meeting of the European League Against Rheumatism in Rome, Italy, June 16 - 19.

* The recommended starting dose of Cimzia for adult patients with rheumatoid arthritis is 400 mg (as 2 injections of 200 mg each on one day) at weeks 0, 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks. Methotrexate should be continued during treatment with Cimzia where appropriate.

Tweede bericht.
New data from EMBLEM(TM) study shows pipeline drug epratuzumab provided significant efficacy for patients suffering from moderate to severe systemic lupus erythematosus
Statistically significant* and clinically meaningful differences of the epratuzumab 600 mg weekly and 1,200 mg every other week dose groups compared to the placebo group were achieved, with responders rates twice those of placebo

Treatment differences were observed as early as week 8, with further improvement to week 12

Epratuzumab 600 mg weekly was associated with greater BILAG improvement (from A/B to C/D) than placebo in affected body systems, with particularly prominent efficacy in cardiorespiratory and neuropsychiatric systems

Rome, June 16th, 2010 - UCB (EURONEXT: UCB) and Immunomedics Inc. (NASDAQ:IMMU) announced new lupus drug candidate, epratuzumab, provided a significant reduction in disease activity in patients with moderate to severe active systemic lupus erythematosus (SLE). Data presented at the European League Against Rheumatism (EULAR) meeting in Rome from the phase IIb study, EMBLEM(TM), showed the clinical efficacy of epratuzumab in patients with SLE.

"We are very encouraged by the findings of this new study which demonstrate that in a patient population with predominantly severe disease activity, epratuzumab is improving patients' health as quickly as week 12, with the emergence of improvements as early as week 8," commented lead study investigator Daniel J. Wallace, M.D., Clinical Professor of Medicine, David Geffen School of Medicine, UCLA. He added, "In a short study, such as this one, seeing this level of patient improvement so rapidly is a hopeful sign of the drug's potential to become an effective new treatment option."

EMBLEM(TM) was a 12-week, multicenter, phase IIb, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of epratuzumab, and to define a dose and regimen in patients with moderate to severe SLE. The primary efficacy measure in EMBLEM(TM) was a combined response index endpoint including several indices of SLE disease activity, primarily emphasizing BILAG**.

In the EMBLEM(TM) study, combined responder index rates were numerically superior in all epratuzumab groups than in the placebo group, reaching statistical significance in the epratuzumab 600 mg weekly group (P=0.0265*) and the combined group of all 74 patients who received a cumulative dose of 2,400 mg (P=0.0239*) during the 12-week treatment cycle. In both these groups, responder rates were twice those of placebo.

Based on analysis of improvement in BILAG 2004 by body system in EMBLEM(TM), most patients had symptom reduction or absence of active disease within specific body systems after treatment with epratuzumab. Efficacy was particularly prominent in cardiorespiratory and neuropsychiatric systems in which symptom improvements are often difficult to achieve. This BILAG analysis reported the results for the BILAG improvement component of the combined response index in body systems for which a sufficient number of patients per treatment group had baseline disease activity that allowed an assessment of response. These systems were: musculoskeletal, mucocutaneous, cardiorespiratory, neuropsychiatric, constitutional and renal.

"Achieving a BILAG improvement without worsening, especially at an early timepoint such as week 12, is encouraging, as the BILAG 2004 evaluates nine different organ systems affected by SLE, including constitutional, mucocutaneous, neuro-psychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal and haematological. In lupus, a disease that has not seen a new drug approved in over fifty years, epratuzumab shows encouraging signs of being able to improve patient lives in this devastating and life altering disease." said Kenneth Kalunian, M.D. Associate Director of the Center for Innovative Therapy, Professor in the Division of Rheumatology, Allergy and Immunology in the School of Medicine at UCSD.

Epratuzumab was associated with a similar incidence of serious adverse events (including infections) and infusion reactions compared to placebo.

Epratuzumab is a humanised monoclonal antibody targeting CD22 and modulating B-cell activity. Although the exact role of CD22 is not fully understood, it is considered to be a regulator of B cell function. B-cells are known to contribute to SLE by producing antibodies against the body's own cells and tissues, causing the immune system to turn on itself, resulting in inflammation and tissue damage. Epratuzumab is an anti-B-cell therapeutic, because of its ability to modulate B cell function without depleting a large portion of these lymphocytes.

* p values were not adjusted for multiple comparisons
**BILAG (British Isles Lupus Assessment Group) is a comprehensive scoring system for assessing both current SLE disease activity and changes in that activity since the patient was last seen.

Derde bericht.
Two-year Cimzia® (certolizumab pegol) data from study showed sustained improvements in household productivity and increased participation in social activities for rheumatoid arthritis patients

Treatment with Cimzia® monotherapy* was associated with increased productivity inside the home and increased participation in family, social and leisure activities[1]

Improvements in productivity and increased participation in social activities were reported rapidly, as early as week 4, and sustained through 2 years of monotherapy treatment[1]

ROME June 16th, 2010, 08.30 CET - UCB today announced new data presented at the European League Against Rheumatism (EULAR) annual congress in Rome showing that Cimzia®, the only approved PEGylated anti-TNF, provided rapid and sustained improvements in household productivity and increased participation in social activities for adult patients living with active rheumatoid arthritis (RA).[1]

"The target of RA treatment is to provide rapid and sustained relief from disease pain and symptoms thus enabling patients to perform household, social, leisure and family activities, the things that are really important," said Dr Vibeke Strand, Adjunct Clinical Professor in the Division of Immunology and Rheumatology, at Stanford University, California, and lead author. "Observations, such as those made in this study with certolizumab pegol, suggest that efficacious treatments can significantly improve productivity and improve the quality of life for patients."

Patients in FAST4WARD(TM) were randomised to Cimzia® 400 mg every 4 weeks or placebo for 24 weeks.* Those who completed or withdrew on/after Week 12 were eligible to enter an open-label extension (OLE) study of Cimzia® 400 mg every 4 weeks as per protocol.* This analysis focuses on Cimzia® completers who entered the OLE study and had 2 years (100 weeks) of Cimzia® exposure from baseline.

The Work Productivity Survey (WPS-RA) used in the study, is a validated questionnaire that evaluated a variety of measures including household productivity - assessed as missed days of household work, days with reduced household productivity and rate of RA impact on household work productivity - as well as the number of missed days of family, social and leisure activities.[1]

The WPS-RA was assessed every four weeks starting at baseline for the first 6 months and every 3 months thereafter, with analyses conducted on observed data from the FAST4WARD(TM) phase III trial open label extension study (FAST4WARD(TM) OLE).[1] Eligibility criteria for the open label extension included participation in the FAST4WARD(TM) study for at least 12 weeks of blinded treatment, without being withdrawn for a possible drug related adverse event or non-compliance.[1]

Following Cimzia® monotherapy treatment, patients reported a rapid improvement in productivity within the home.[1] By Week 4, patients reported a lower rate of RA interference with household productivity than at baseline (3.7 rate compared with 5.8 rate, on a 0-10 scale where 0=no interference and 10=complete interference).[1] These improvements were sustained and by week 100, only 1 household work day (on average) was missed and only 1.1 household work day with reduced productivity was reported, per month.[1]

These improvements in productivity within the home were seen in the majority of patients.[1] In fact, by week 100, about 60% of patients did not miss any day of household work and about 90% of patients reported ≤4 missed days of household work per month.[1]

Patients treated with Cimzia® monotherapy also reported rapid and sustained improvements in participation in family, social, and leisure activities.[1] By Week 4, Cimzia®-treated patients missed on average fewer days per month of family, social, or leisure activities than at baseline (1.5 days compared with 5.0 days).[1] By Week 100, on average 0.3 days of family, social, or leisure activities were missed, per month.[1] At Week 100, over 80% of patients did not miss any days of family, social, or leisure activities, per month, and all patients reported ≤ 4 days of family, social, or leisure activities, missed per month.[1]

The monthly improvements in household productivity reported by Cimzia® patients resulted into annualized cumulative gains, with average incremental gains over baseline of:

108 full days of household work by 1 year and 199 by 2 years[1]

136 more productive days of household work by 1 year and 245 by 2 years[1]

58 days of social, family, or leisure activities by 1 year and 107 by 2 years[1]

In Cimzia®'s pivotal clinical trials reported serious adverse reactions included infections (including tuberculosis) and malignancies (including lymphoma). The most common adverse reactions belonged to the system organ classes Infections and Infestations, reported in 15.5% of patients on Cimzia® and 7.6% of patients on placebo, and General disorders and administration site conditions, reported in 10.0% of patients on Cimzia® and 9.7% of patients on placebo. A pooled analysis of the safety data showed there was a low incidence of injection site pain (1.5%) and a low level of discontinuations due to adverse events (5%). Cimzia® demonstrated a favorable risk-benefit profile in patients with at least up to two years of drug exposure.

* Cimzia®, in combination with methotrexate (MTX), is indicated for the treatment of moderate to severe, active rheumatoid arthritis (RA) in adult patients when the response to disease-modifying antirheumatic drugs (DMARDs) including methotrexate, has been inadequate. Cimzia® can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. The recommended starting dose of Cimzia® for adult patients with rheumatoid arthritis is 400 mg (as 2 injections of 200 mg each on one day) at weeks 0, 2 and 4, followed by a maintenance dose of 200 mg every 2 weeks. MTX should be continued during treatment with Cimzia® where appropriate.