- Late-breaking, investigational 16-week data presented from the CIMPASI-1 and CIMPASI-2 trials showing CIMZIA demonstrated statistically and clinically significant improvements for patients with moderate-to-severe chronic plaque psoriasis
- Four-year data from the CIMZIA RAPID-PSA study showing long-term maintenance of improvement in the joint and skin manifestations of psoriatic arthritis regardless of prior exposure to an anti-TNF, or as monotherapy without concomitant use of disease modifying anti-rheumatic drugs (DMARDs)
ORLANDO, Fla., March 04, 2017 (GLOBE NEWSWIRE) -- UCB (Euronext:UCB) and Dermira, Inc. (NASDAQ:DERM) today announced 16-week, investigational results from the CIMPASI-1 and CIMPASI-2 Phase 3 trials at the 75th Annual Meeting of the American Academy of Dermatology (AAD) in Orlando, Florida.1 Results from the trials showed that CIMZIA® (certolizumab pegol) demonstrated significant improvements in patients with moderate-to-severe chronic plaque psoriasis versus placebo. In addition to previously reported co-primary endpoints, new data presented in an oral presentation at AAD showed the percentage of patients who achieved 90% or greater disease improvement from baseline, as measured by the Psoriasis Area and Severity Index (PASI 90). Additionally, data analyses from the RAPID-PsA Phase 3 study were presented evaluating the long-term effect of CIMZIA in adult patients with active psoriatic arthritis (PsA).
“The 16-week primary results from CIMPASI-1 and CIMPASI-2 showed that treatment with CIMZIA provided significant benefit to patients living with chronic plaque psoriasis, which is important given that the disease is historically difficult to treat and therefore requires multiple treatment options,” said Alice Gottlieb, M.D., Ph.D., Professor of Dermatology, Department of Dermatology, New York Medical College, at Metropolitan Hospital and lead presenter of the data.
“The CIMPASI-1 and CIMPASI-2 clinical results presented today support our belief that CIMZIA may one day benefit people living with moderate-to-severe plaque psoriasis,” said Luis Peña, chief development officer at Dermira. “We are committed to providing patients with access to a new treatment option for psoriasis that may also one day contribute to improvements in their overall quality of life.”
“We’re pleased to present the clinical results from CIMPASI-1, CIMPASI-2, and RAPID-PsA at AAD this year,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President at UCB, Immunology Patient Value Unit, UCB. “At UCB, we are driven foremost by providing value to patients, and these results demonstrate the breadth of our immunology portfolio for people living with plaque psoriasis and psoriatic arthritis. We look forward to continuing our partnership with Dermira to bring CIMZIA to these patients.”
The results of the initial 16-week treatment period of CIMPASI-1 and CIMPASI-2 offer important insights for the potential use and the value of CIMZIA in adult patients with moderate to severe chronic plaque psoriasis. Researchers reported that CIMZIA showed clinically meaningful improvements in the PGA, PASI 75 and PASI 90 endpoints at week 16 compared to placebo at both treatment doses (400mg, 200mg).
Topline results from CIMPASI-1 and CIMPASI-2 were previously announced. The identically designed trials evaluated the percentage of patients who achieved a 75% or greater disease improvement from baseline as measured by the Psoriasis Area and Severity Index (PASI 75), as well as the percentage of patients achieving at least a two-point improvement on a five-point Physician’s Global Assessment (PGA) scale to a final score representing clear or almost clear skin, each compared with placebo, at week 16.2
Researchers reported that the most frequent adverse events (AEs) in CIMPASI-1 and CIMPASI-2 through week 16 were upper respiratory tract infections, and serious AEs were infrequent. The adverse event profile across both trials appeared consistent with the adverse event profiles observed with CIMZIA in other indications.2 CIMZIA is not currently approved for the treatment of psoriasis by any regulatory authority worldwide.
CIMPASI-1 16-week Results1
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A total of 234 patients with moderate-to-severe chronic plaque psoriasis were randomized in the CIMPASI-1 trial to one of three dosing arms—400 mg every two weeks (n=88), 400 mg at weeks 0, 2, and 4 followed by 200 mg every two weeks (n=95), or placebo every two weeks (n=51).
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At week 16, the response rate for patients who achieved a PASI 75 was 75.8% for patients receiving the 400 mg dose every two weeks and 66.5% for patients receiving the 200 mg dose every two weeks, compared to 6.5% for patients receiving placebo.
- The response rate for patients achieving at least a two-point improvement to a final score of clear or almost clear skin on the PGA scale at week 16 was 57.9% for the 400 mg dose-treated patients and 47.0% for the 200 mg dose-treated patients, compared to 4.2% for the patients receiving placebo.
- At week 16, the response rate for patients who achieved a PASI 90 was 43.6% for patients receiving the 400 mg dose every two weeks and 35.8% for patients receiving the 200 mg dose every two weeks, compared to 0.4% for the patients receiving placebo.
CIMPASI-2 16-week Results1
- A total of 227 patients with moderate-to-severe chronic plaque psoriasis were randomized in the CIMPASI-2 trial to one of three dosing arms—400 mg every two weeks (n=87), 400 mg at weeks 0, 2, and 4 followed by 200 mg every two weeks (n=91), or placebo every two weeks (n=49).
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At week 16, the response rate for patients who achieved a PASI 75 was 82.6% for patients receiving the 400 mg dose every two weeks and 81.4% for patients receiving the 200 mg dose every two weeks, compared to 11.6% for the patients receiving placebo.
- The response rate for patients achieving at least a two-point improvement to a final score of clear or almost clear skin on the PGA scale at week 16 was 71.6% for the 400 mg dose-treated patients and 66.8% for the 200 mg dose-treated patients, compared to 2.0% for the patients receiving placebo.
- At week 16, the response rate for patients who achieved a PASI 90 was 55.4% for patients receiving the 400 mg dose every two weeks and 52.6% for patients receiving the 200 mg dose every two weeks, compared to 4.5% for the patients receiving placebo.
Additional data reported from a key secondary endpoint also found that patients receiving the 400mg and 200 mg dose reported significant improvements in their quality of life compared to patients who received placebo only. CIMZIA showed a mean improvement from baseline in the Dermatology Life Quality Index (DLQI) score compared to placebo, at both doses in both the CIMPASI-1 (decrease of 10.2 at 400 mg and 9.3 at 200 mg vs. 3.3; p<0.001) and CIMPASI-2 (decrease of 10.0 at 400 mg and 10.4 at 200 mg vs. 3.8; p<0.001) clinical trials, at week 16.
A decrease in a patient’s DLQI score translates to overall improved satisfaction in the management of their skin condition. DLQI is a widely used and recognized quality of life measurement instrument frequently used across many dermatologic conditions.
RAPID-PsA Results3,4,5
Additionally, three post-hoc data analyses from the RAPID-PsA four-year open label extension study were presented, providing insight into the long-term impact of CIMZIA on psoriatic arthritis (PsA) patients. RAPID-PsA is a Phase 3, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of CIMZIA. The results of RAPID-PsA were:
- A total of 409 patients with onset active and progressive psoriatic arthritis (PsA) were randomized to one of three dosing arms – to CIMZIA 200 mg every two weeks (n=138), CIMZIA 400 mg every four weeks (n=135), or placebo (n=136) for 24 weeks, followed by dose blind to week 48, and open-label extension to week 216. All patients received a loading dose with CIMZIA 400 mg or placebo at weeks 0, 2, and 4.
- Eligible patients had adult onset active PsA =6 months’ duration as defined by the Classification Criteria for Psoriatic Arthritis (CASPAR) criteria, active psoriatic lesions or a documented history of psoriasis, =3 tender and =3 swollen joints, erythrocyte sedimentation rate =28 mm/hr (Westergren) and/or C-reactive protein greater than the upper limit of normal, and failed =1 DMARD (nonbiologic or biologic).
- For extra-articular manifestations (EAMs) specifically, by week 24, a large proportion of patients with baseline involvement achieved total resolution of the respective EAM (nail psoriasis: 38.5%, enthesitis: 65.2%, dactylitis: 73.8%) Mean scores in all EAMs assessed showed improvements by week 12 and maintained to week 216 for patients completing the study.
- Patients with or without prior anti-TNF exposure experienced improvements in joint and skin manifestations that were maintained over four years. For skin outcomes, these improvements were maintained in patients with and without prior anti-TNF exposure. Additionally, for patients treated with CIMZIA® both with and without concomitant DMARD use, efficacy was maintained over four years.
About Psoriasis
Psoriasis is a common, chronic, immune-mediated inflammatory disorder with primary involvement of the skin. It affects nearly three percent of the world’s population, or approximately 125 million people worldwide. The skin condition affects men and women of all ages and ethnicities. Psoriasis signs and symptoms can vary, but may include red patches of skin covered with silvery scales, dry, cracked skin that may bleed and thickened, pitted or ridged nails.6
About Psoriatic Arthritis
Psoriatic arthritis (PsA) is a condition involving joint inflammation (arthritis) that usually occurs in combination with a skin disorder called psoriasis. Signs and symptoms of PsA include stiff, painful joints with warmth and swelling in the joints and surrounding tissues. In most people with PsA, psoriasis appears before joint problems develop. In some cases, psoriatic arthritis develops prior to the skin changes. Left untreated PsA can be a disabling disease. PsA affects an estimated 3.4 to 8 per 100,000 people. Between 6 and 42 percent of people with psoriasis develop psoriatic arthritis. Psoriasis affects nearly three percent of the world’s population, or approximately 125 million people worldwide.7,8
About Cimzia® In the US
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.
Cimzia® is indicated for the treatment of adults with moderately to severely active rheumatoid arthritis, adults with active psoriatic arthritis (PsA), and adults with active ankylosing spondylitis (AS). In addition, it is indicated 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. See important safety information including risk of serious bacterial, viral and fungal infections and tuberculosis below.
Important Safety Information about Cimzia® in the US
Risk of Serious Infections and Malignancy
Patients treated with Cimzia® are at an increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants such as methotrexate or corticosteroids. Cimzia® should be discontinued if a patient develops a serious infection or sepsis. Reported infections include:
- Active tuberculosis, including reactivation of latent tuberculosis. Patients with tuberculosis have frequently presented with disseminated or extrapulmonary disease. Patients should be tested for latent tuberculosis before Cimzia® use and during therapy. Treatment for latent infection should be initiated prior to Cimzia® use.
- Invasive fungal infections, including histoplasmosis, coccidioidomycosis, candidiasis, aspergillosis, blastomycosis, and pneumocystosis. Patients with histoplasmosis or other invasive fungal infections may present with disseminated, rather than localized disease. Antigen and antibody testing for histoplasmosis may be negative in some patients with active infection. Empiric anti-fungal therapy should be considered in patients at risk for invasive fungal infections who develop severe systemic illness.
- Bacterial, viral and other infections due to opportunistic pathogens, including Legionella and Listeria.
The risks and benefits of treatment with Cimzia® should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Cimzia®, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients treated with TNF blockers, of which Cimzia® is a member. Cimzia® is not indicated for use in pediatric patients.
Patients treated with Cimzia® are at an increased risk for developing serious infections involving various organ systems and sites that may lead to hospitalization or death. Opportunistic infections due to bacterial, mycobacterial, invasive fungal, viral, parasitic, or other opportunistic pathogens including aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis and tuberculosis have been reported with TNF blockers. Patients have frequently presented with disseminated rather than localized disease.
Treatment with Cimzia® should not be initiated in patients with an active infection, including clinically important localized infections. Cimzia® should be discontinued if a patient develops a serious infection or sepsis. Patients greater than 65 years of age, patients with co-morbid conditions, and/or patients taking concomitant immunosuppressants (e.g., corticosteroids or methotrexate) may be at a greater risk of infection. Patients who develop a new infection during treatment with Cimzia® should be closely monitored, undergo a prompt and complete diagnostic workup appropriate for immunocompromised patients, and appropriate antimicrobial therapy should be initiated. Appropriate empiric antifungal therapy should also be considered while a diagnostic workup is performed for patients who develop a serious systemic illness and reside or travel in regions where mycoses are endemic.
Malignancies
During controlled and open-labeled portions of Cimzia® studies of Crohn’s disease and other diseases, malignancies (excluding non-melanoma skin cancer) were observed at a rate of 0.5 per 100 patient-years among 4,650 Cimzia®-treated patients versus a rate of 0.6 per 100 patient-years among 1,319 placebo-treated patients. In studies of Cimzia® for Crohn’s disease and other investigational uses, there was one case of lymphoma among 2,657 Cimzia®-treated patients and one case of Hodgkin lymphoma among 1,319 placebo-treated patients. In Cimzia® RA clinical trials (placebo-controlled and open label), a total of three cases of lymphoma were observed among 2,367 patients. This is approximately 2-fold higher than expected in the general population. Patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of TNF blocker therapy in the development of malignancies is not known.
Malignancies, some fatal, have been reported among children, adolescents, and young adults who received treatment with TNF-blocking agents (initiation of therapy =18 years of age), of which Cimzia® is a member. Approximately half of the cases were lymphoma (including Hodgkin’s and non-Hodgkin’s lymphoma), while the other cases represented a variety of different malignancies and included rare malignancies associated with immunosuppression and malignancies not usually observed in children and adolescents. Most of the patients were receiving concomitant immunosuppressants.
Cases of acute and chronic leukemia have been reported with TNF-blocker use. Even in the absence of TNF-blocker therapy, patients with RA may be at a higher risk (approximately 2-fold) than the general population for developing leukemia.
Postmarketing cases of hepatosplenic T-cell lymphoma (HSTCL), a rare type of T-cell lymphoma that has a very aggressive disease course and is usually fatal, have been reported in patients treated with TNF blockers, including Cimzia®. The majority of reported TNF blocker cases occurred in adolescent and young adult males with Crohn’s disease or ulcerative colitis. Almost all of these patients had received treatment with the immunosuppressants azathioprine and/or 6-mercaptopurine (6-MP) concomitantly with a TNF blocker at or prior to diagnosis. Carefully assess the risks and benefits of treatment with Cimzia®, especially in these patient types.
Melanoma and Merkel cell carcinoma have been reported in patients treated with TNF-antagonists, including Cimzia®. Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer.
Heart Failure
Cases of worsening congestive heart failure (CHF) and new onset CHF have been reported with TNF blockers. Cimzia® has not been formally studied in patients with CHF. Exercise caution when using Cimzia® in patients who have heart failure and monitor them carefully.
Hypersensitivity
Symptoms compatible with hypersensitivity reactions, including angioedema, dyspnea, hypotension, rash, serum sickness, and urticaria, have been reported rarely following Cimzia® administration. Some of these reactions occurred after the first administration of Cimzia®. If such reactions occur, discontinue further administration of Cimzia® and institute appropriate therapy.
Hepatitis B Reactivation
Use of TNF blockers, including Cimzia®, has been associated with reactivation of hepatitis B virus (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Test patients for HBV infection before initiating treatment with Cimzia®. Exercise caution in prescribing Cimzia® for patients identified as carriers of HBV, with careful evaluation and monitoring prior to and during treatment. In patients who develop HBV reactivation, discontinue Cimzia® and initiate effective anti-viral therapy with appropriate supportive treatment.
Neurologic Reactions
Use of TNF blockers, including Cimzia®, has been associated with rare cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disease, including multiple sclerosis, and with peripheral demyelinating disease, including Guillain-Barré syndrome. Rare cases of neurological disorders, including seizure disorder, optic neuritis, and peripheral neuropathy have been reported in patients treated with Cimzia®. Exercise caution in considering the use of Cimzia® in patients with these disorders.
Hematologic Reactions
Rare reports of pancytopenia, including aplastic anemia, have been reported with TNF blockers. Medically significant cytopenia (e.g., leukopenia, pancytopenia, thrombocytopenia) has been infrequently reported with Cimzia®. Advise all patients to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias or infection (e.g., persistent fever, bruising, bleeding, pallor) while on Cimzia®. Consider discontinuation of Cimzia® therapy in patients with confirmed significant hematologic abnormalities.
Drug Interactions
An increased risk of serious infections has been seen in clinical trials of other TNF blocking agents used in combination with anakinra or abatacept. Formal drug interaction studies have not been performed with rituximab or natalizumab; however, because of the nature of the adverse events seen with these combinations with TNF blocker therapy, similar toxicities may also result from the use of Cimzia® in these combinations. Therefore, the combination of Cimzia® with anakinra, abatacept, rituximab, or natalizumab is not recommended. Interference with certain coagulation assays has been detected in patients treated with Cimzia®. There is no evidence that Cimzia® therapy has an effect on in vivo coagulation. Cimzia® may cause erroneously elevated aPTT assay results in patients without coagulation abnormalities.
Autoimmunity
Treatment with Cimzia® may result in the formation of autoantibodies and, rarely, in the development of a lupus-like syndrome. Discontinue treatment if symptoms of lupus-like syndrome develop.
Immunizations
Do not administer live vaccines or live-attenuated vaccines concurrently with Cimzia®.
Adverse Reactions
In controlled Crohn’s clinical trials, the most common adverse events that occurred in =5% of Cimzia® patients (n=620) and more frequently than with placebo (n=614) were upper respiratory infection (20% Cimzia®, 13% placebo), urinary tract infection (7% Cimzia®, 6% placebo), and arthralgia (6% Cimzia®, 4% placebo). The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 8% for Cimzia® and 7% for placebo.
In controlled RA clinical trials, the most common adverse events that occurred in =3% of patients taking Cimzia® 200 mg every other week with concomitant methotrexate (n=640) and more frequently than with placebo with concomitant methotrexate (n=324) were upper respiratory tract infection (6% Cimzia®, 2% placebo), headache (5% Cimzia®, 4% placebo), hypertension (5% Cimzia®, 2% placebo), nasopharyngitis (5% Cimzia®, 1% placebo), back pain (4% Cimzia®, 1% placebo), pyrexia (3% Cimzia®, 2% placebo), pharyngitis (3% Cimzia®, 1% placebo), rash (3% Cimzia®, 1% placebo), acute bronchitis (3% Cimzia®, 1% placebo), fatigue (3% Cimzia®, 2% placebo). Hypertensive adverse reactions were observed more frequently in patients receiving Cimzia® than in controls. These adverse reactions occurred more frequently among patients with a baseline history of hypertension and among patients receiving concomitant corticosteroids and non-steroidal anti-inflammatory drugs. Patients receiving Cimzia® 400 mg as monotherapy every 4 weeks in RA controlled clinical trials had similar adverse reactions to those patients receiving Cimzia® 200 mg every other week. The proportion of patients who discontinued treatment due to adverse reactions in the controlled clinical studies was 5% for Cimzia® and 2.5% for placebo.
The safety profile for patients with Psoriatic Arthritis (PsA) treated with CIMZIA® was similar to the safety profile seen in patients with RA and previous experience with Cimzia®.
The safety profile for AS patients treated with Cimzia® was similar to the safety profile seen in patients with RA.
For full prescribing information, please visit www.ucb.com
CIMZIA® is a registered trademark of the UCB Group of Companies.
About Cimzia® in the EU/EEA
In the EU, Cimzia® in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active RA in adult patients inadequately responsive to disease-modifying anti-rheumatic drugs (DMARDs) including MTX.
Cimzia® can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate. CIMZIA® in combination with MTX is also indicated for the treatment of severe, active and progressive RA in adults not previously treated with MTX or other DMARDs.
Cimzia® has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function, when given in combination with MTX.
Cimzia®, in combination with MTX, is also indicated for the treatment of active psoriatic arthritis in adults when the response to previous DMARD therapy has been inadequate. Cimzia® can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate.
Cimzia® is also indicated in the EU for the treatment of adult patients with severe active axial spondyloarthritis (axSpA), comprising:
- Ankylosing spondylitis (AS) - adults with severe active AS who have had an inadequate response to, or are intolerant to non-steroidal anti-inflammatory drugs (NSAIDs).
- Axial spondyloarthritis (axSpA) without radiographic evidence of AS - adults with severe active axSpA without radiographic evidence of AS but with objective signs of inflammation by elevated C-reactive protein (CRP) and/or Magnetic Resonance Imaging (MRI) who have had an inadequate response to, or are intolerant to NSAIDs.4
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