UCB announced today two new regulatory filings with the US Food and Drug Administration (FDA) and with the European Medicines Agency (EMA) to extend the marketing authorization for Cimzia® (certolizumab pegol) for the treatment of adult patients with active psoriatic arthritis (PsA) and for adult patients with active axial spondyloarthritis (axSpA). The regulatory filings for two new indications for certolizumab pegol are now under review by the US FDA and EMA.
"We are committed to providing treatments for patients with severe diseases such as PsA and axSpA which can affect adults at a very productive and active time of their lives. These new regulatory filings bring us one step closer to supporting more people living with immunological conditions and to building UCB's immunology franchise," said Professor Dr. Iris Loew-Friedrich, Chief Medical Officer and Executive Vice President UCB. "The clinical study supporting the axSpA filing represents the first Phase 3 study with an anti-TNF to include axSpA patients with and without definitive radiographic evidence of structural damage to the spine. Similarly the study supporting the PsA filing was the first randomized, controlled study of an anti-TNF in PsA to include patients with and without prior anti-TNF exposure."
Certolizumab pegol is a Fc-free, PEGylated anti-TNF. In the US, certolizumab pegol is approved for the treatment of adults with moderately to severely active rheumatoid arthritis. It is also approved for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy. Certolizumab pegol is marketed under the trade name Cimzia®.(1)
In the EU, certolizumab pegol in combination with methotrexate (MTX) is approved for the treatment of moderate to severe active rheumatoid arthritis in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs including MTX. Certolizumab pegol can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.(2)
PsA is a chronic inflammatory condition which affects both the skin and joints.3 It can cause skin and nail abnormalities and can lead to significant joint damage and disability over time.(3,4)
The RAPIDTM-PsA study was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of certolizumab pegol in patients with adult onset active and progressive PsA. Patients (n=409) received certolizumab pegol 400 mg on weeks 0, 2 and 4 and were then randomized (1:1:1) to receive either certolizumab pegol 200 mg every 2 weeks, 400 mg every 4 weeks or placebo. One clinical primary endpoint of the study was the ACR20 response at week 12. The second clinical primary endpoint was the difference from baseline to week 24 in the van der Heijde modified Total Sharp Score (mTSS) of radiographic changes.(5)
AxSpA is a form of spondyloarthritis that affects mainly the spine and sacroiliac joints, and includes ankylosing spondylitis (AS) and axSpA without definitive radiographic evidence of AS (nr-axSpA).(6) The symptoms of AS can vary, but most people experience back pain and stiffness due to inflammation.(7) People with nr-axSpA can have similar signs and symptoms to AS, but do not have definitive X-ray evidence of structural damage.(8)
The RAPIDTM-axSpA study was a Phase 3, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of certolizumab pegol in patients with active axSpA. Patients (n=325) received certolizumab pegol 400 mg on weeks 0, 2 and 4 and were then randomized (1:1:1) to receive certolizumab pegol 200 mg every two weeks, 400 mg every four weeks or placebo. The primary endpoint of the study was the ASAS20 response rate at week 12.(9)
About SpA (6)
SpA is the overall name of a family of inflammatory rheumatic diseases that can affect the spine and peripheral joints, ligaments and tendons. There are two main types of clinical presentation of SpA - axSpA (symptoms predominantly related to the spine) and peripheral SpA (symptoms predominantly related to the peripheral joints).
About Psoriatic Arthritis (3)
Signs and symptoms of PsA include stiff, painful, swollen joints with reduced mobility, and changes to the nails. PsA affects approximately 0.24 percent of the population worldwide. Genetic and environmental factors play a role in PsA, and the disease usually occurs between the ages of 30 and 50.
About AS (6,7,10)
AS is a chronic inflammatory rheumatic disease of the spine and is the most defined subset of axSpA. The symptoms of AS can vary, but most people experience back pain and stiffness due to inflammation which can proceed to fusion of the vertebrae. The condition can be severe, with around 1 in 10 people at risk of long-term disability. The condition usually occurs between 15 and 35 years of age, and rarely starts in old age, with prevalence estimated to be between 0.1% - 1.1% of the population. AS is more common in men than in women. Ankylosing spondylitis is hereditary and the major gene that causes this disease is HLA-B27.
About axSpA without radiographic evidence of AS (8)
Patients with no definitive sacroiliitis on conventional radiographs but similar clinical features and showing either sacroiliitis on MRI or who are HLA-B27 positive have axSpA without radiographic evidence of AS (non-radiographic axSpA [nr-axSpA]). There is limited epidemiological data for nr-axSpA.
About ACR20
ACR20 response is the proportion of patients achieving a 20% improvement in tender and swollen joint counts, together with a 20% improvement in at least 3 of: global disease activity assessed by observer, global disease activity assessed by patient, patient assessment of pain, physical disability score or acute phase response (c-reactive protein [CRP] measurement).
About ASAS20
The Assessment of SpondyloArthritis international Society (ASAS20) improvement criteria is defined as an improvement of at least 20% and absolute improvement of at least one unit on a 0-10 scale in at least three of the four following domains: patient global assessment, pain assessment, patient function, and inflammation and the absence of deterioration in the remaining domain.
About CIMZIA®
Cimzia® is the only Fc-free, PEGylated anti-TNF (Tumor Necrosis Factor). Cimzia® has a high affinity for human TNF-alpha, selectively neutralizing the pathophysiological effects of TNF-alpha. Over the past decade, TNF-alpha has emerged as a major target of basic research and clinical investigation. This cytokine plays a key role in mediating pathological inflammation, and excess TNF-alpha production has been directly implicated in a wide variety of diseases. The U.S. Food and Drug Administration (FDA) has approved Cimzia® for reducing signs and symptoms of Crohn's disease and maintaining clinical response in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy and for the treatment of adults with moderately to severely active rheumatoid arthritis. Cimzia® in combination with MTX is approved in the EU for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying antirheumatic drugs (DMARDs) including MTX. Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. UCB is also developing Cimzia® in other autoimmune disease indications. Cimzia® is a registered trademark of UCB PHARMA S.A.
About UCB
UCB, Brussels, Belgium is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8 500 people in about 40 countries, the company generated revenue of EUR 3.2 billion in 2011. UCB is listed on Euronext Brussels (symbol: UCB).
1. Cimzia® US Prescribing Information. Accessed 5th February 2013 from http://www.ucb.com/_up/ucb_com_products/documents/Cimzia_COL_11_2012.pdf
2. Cimzia® EU Summary of Product Characteristics. Accessed 5th February 2013 from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf
3. Psoriatic Arthritis, Genetics Home Reference. Accessed 5th February 2013 from http://ghr.nlm.nih.gov/condition/psoriatic-arthritis
4. Schett G., Coates L.C. et al. Structural damage in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: traditional views, novel insights gained from TNF blockade, and concepts for the future. Arthritis Res Ther. 2011 May 25;13 Suppl 1:S4.
5. ClinTrials.gov. Certolizumab Pegol in subjects with adult onset active and progressive psoriatic arthritis. Accessed 5th February 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01087788?term=certolizumab+pegol+and+psoriatic+arthritis&rank=1
6. Spondyloarthritis (Spondyloarthropathies). American College of Rheumatology. Accessed 5th February 2013 from http://www.rheumatology.org/practice/clinical/patients/diseases_and_conditions/spondyloarthritis.pdf#toolbar=1
7. Ankylosing Spondylitis, NHS Choices. Accessed 5th February 2013 from http://www.nhs.uk/conditions/Ankylosing-spondylitis/Pages/Introduction.aspx
8. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis, Assessment of Spondyloarthritis International Society. Accessed 5th February 2013 from http://www.asas-group.org/education.php?id=01
9. ClinTrials.gov. Certolizumab pegol in subjects with active axial spondyloarthritis. Accessed 5th February 2013 from http://www.clinicaltrials.gov/ct2/show/NCT01087762?term=certolizumab+pegol+and+axial+spondyloarthritis&rank=1
10. Guideline on Clinical Investigation of Medicinal Products for the Treatment of Ankylosing Spondylitis, European Medicines Agency. Accessed February 13th 2013 from www.ema.europa.eu/ema/pages/includes/document/open_document.jsp?webContentId=WC500003424