Dermira Completes Patient Enrollment for Third CIMZIA® (certolizumab pegol) Phase 3 Clinical Trial in Psoriasis Program and Updates Guidance for Release of Topline Data
Enrollment for All Three Phase 3 Clinical Trials in Patients with Moderate-to-Severe Plaque Psoriasis Completed
Dermira Plans to Announce Topline Data for Phase 3 Trials by End of First Quarter 2017
MENLO PARK, Calif., Jan. 08, 2016 (GLOBE NEWSWIRE) -- Dermira, Inc. (NASDAQ: DERM), a biopharmaceutical company dedicated to identifying, developing and commercializing innovative, differentiated therapies to improve the lives of patients with dermatologic diseases, today announced the completion of patient enrollment for the CIMPACT clinical trial of CIMZIA® (certolizumab pegol) in adult patients with moderate-to-severe chronic plaque psoriasis. The CIMPACT study is the third and final clinical trial of the CIMZIA Phase 3 development program in moderate-to-severe chronic plaque psoriasis to complete enrollment, following the completion of enrollment for the CIMPASI-2 Phase 3 trial in September 2015 and CIMPASI-1 Phase 3 trial in November 2015. CIMZIA is not currently approved for the treatment of psoriasis by any regulatory authority worldwide.
Based on completion of enrollment in all three Phase 3 trials of the psoriasis program, Dermira now expects to announce topline data for the trials by the end of the first quarter of 2017, following completion of the 48-week blinded treatment period in each of the trials. Previously, the company had expected to announce topline data in 2017.
"I am very pleased with the completion of patient enrollment for CIMPACT, our third and final CIMZIA Phase 3 clinical trial in psoriasis, which, similar to our CIMPASI-1 and CIMPASI-2 CIMZIA Phase 3 trials, was achieved ahead of schedule," stated Tom Wiggans, chairman and chief executive officer of Dermira. "We are excited about the continued collaboration with UCB and progress towards our goal of bringing this important potential therapy to the millions of patients with moderate-to-severe plaque psoriasis, an often debilitating skin disease."
As previously disclosed, Dermira expects that marketing applications for CIMZIA in adults with moderate-to-severe chronic plaque psoriasis in the U.S. and EU will be based on the results of the primary endpoints at 12 or 16 weeks, as applicable, with additional data collected through week 48 to provide further support for dosing recommendations. While any marketing approval will be based on the overall results of the trials, the company expects that marketing approval for CIMZIA in moderate-to-severe chronic plaque psoriasis in the U.S. and EU will require that each of the CIMPASI trials (CIMPASI-1 and CIMPASI-2) demonstrates that CIMZIA produces a statistically significant improvement relative to placebo in each of its co-primary endpoints, which are the proportion of patients who achieve (1) a 75% improvement in disease severity, as measured by the Psoriasis Area and Severity Index (PASI 75), and (2) an improvement of at least two points to a final score representing clear or almost clear skin on a five-point Physician's Global Assessment scale (PGA), each as measured at week 16. In addition, the company expects that EU approval for CIMZIA in moderate-to-severe plaque psoriasis will require that the CIMPACT trial demonstrates that CIMZIA produces a statistically significant improvement relative to placebo and to etanercept (marketed as Enbrel®*) in PASI 75, as measured at week 12.
About the CIMZIA Phase 3 Clinical Program
The Phase 3 clinical development program, which is led by Dermira in collaboration with UCB, is designed to evaluate the efficacy and safety of certolizumab pegol in the treatment of adult patients with moderate-to-severe chronic plaque psoriasis. It consists of three studies that have enrolled a total of approximately 1,000 patients, including patients with and without prior treatment experience with biologic products.
The two CIMPASI studies (CIMPASI-1 and CIMPASI-2), each of which has completed enrollment of approximately 225 patients, are randomized, blinded, parallel group, placebo-controlled, multi-center trials designed to evaluate the efficacy and safety of certolizumab pegol in the treatment of patients with moderate-to-severe chronic plaque psoriasis. The third study, CIMPACT, which has now completed enrollment of approximately 540 patients, is a randomized, blinded, parallel group, placebo-controlled and blinded, active-controlled, multi-center study with a primary objective of comparing the efficacy and safety of certolizumab pegol to placebo in the treatment of patients with moderate-to-severe chronic plaque psoriasis. A secondary objective of the CIMPACT trial is to compare the efficacy of certolizumab pegol to etanercept.
The primary endpoint in CIMPACT, the placebo- and active-controlled study, is PASI 75, compared with placebo, as measured at week 12. CIMPASI-1 and CIMPASI-2, the placebo-controlled studies, have co-primary endpoints comprising both PASI 75 and PGA, each compared with placebo, at week 16. Patients in each trial may receive blinded treatment for up to 48 weeks. Patients in each study may receive open-label treatment with certolizumab pegol for up to an additional 96 weeks.
Under the terms of the agreement announced in July 2014, Dermira obtained exclusive rights to develop certolizumab pegol in psoriasis in the United States, Canada and the European Union. Subject to regulatory approval of CIMZIA in psoriasis, Dermira is granted an exclusive commercial license to market CIMZIA to dermatologists in the U.S. and Canada.
*ENBREL® (etanercept) is a registered trademark of Amgen Inc.
CIMZIA® is a registered trademark of the UCB Group of Companies.
Psoriasis is a common, chronic, relapsing, immune-mediated, inflammatory disorder with primary involvement of the skin. It affects two to three percent of the world's population – approximately 125 million people worldwide. Psoriasis signs and symptoms can vary from person to person but may include red patches of skin covered with silvery scales, dry, cracked skin that may bleed and thickened, pitted or ridged nails.
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.
About CIMZIA in the U.S.2
In the U.S., CIMZIA is approved for the treatment of adults with moderately to severely active rheumatoid arthritis, for the treatment of adults with active psoriatic arthritis (PsA) and for adults with active ankylosing spondylitis (AS). In addition, it is 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.
Important Safety Information about CIMZIA in the U.S.
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.
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.
Periodic skin examinations are recommended for all patients, particularly those with risk factors for skin cancer.
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.
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.
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.
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.
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 a PTT assay results in patients without coagulation abnormalities.
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.
Do not administer live vaccines or live-attenuated vaccines concurrently with CIMZIA.
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
About CIMZIA in the EU/EEA3
CIMZIA in combination with methotrexate (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. CIMZIA, in combination with MTX, is 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 approved 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.
Important Safety Information about CIMZIA in the EU/EEA
CIMZIA was studied in 4,049 patients with rheumatoid arthritis (RA) in controlled and open label trials for up to 92 months. The commonly reported adverse reactions (1-10%) in clinical trials with CIMZIA and post-marketing were viral infections (includes herpes, papillomavirus, influenza), bacterial infections (including abscess), rash, headache (including migraine), asthaenia, leukopaenia (including lymphopaenia, neutropaenia), eosinophilic disorder, pain (any sites), pyrexia, sensory abnormalities, hypertension, pruritus (any sites), hepatitis (including hepatic enzyme increase), injection site reactions, and nausea. Serious adverse reactions include sepsis, opportunistic infections, tuberculosis, herpes zoster, lymphoma, leukaemia, solid organ tumours, angioneurotic oedema, cardiomyopathies (includes heart failure), ischemic coronary artery disorders, pancytopaenia, hypercoagulation (including thrombophlebitis, pulmonary embolism), cerebrovascular accident, vasculitis, hepatitis/hepatopathy (includes cirrhosis), and renal impairment/nephropathy (includes nephritis). In RA controlled clinical trials, 4.4% of patients discontinued taking CIMZIA due to adverse events vs. 2.7% for placebo.
CIMZIA is contraindicated in patients with hypersensitivity to the active substance or any of the excipients, active tuberculosis or other severe infections such as sepsis or opportunistic infections or moderate-to-severe heart failure.
Serious infections including sepsis, tuberculosis and opportunistic infections have been reported in patients receiving CIMZIA. Some of these events have been fatal. Monitor patients closely for signs and symptoms of infections including tuberculosis before, during and after treatment with CIMZIA. Treatment with CIMZIA must not be initiated in patients with a clinically important active infection. If an infection develops, monitor carefully and stop CIMZIA if infection becomes serious. Before initiation of therapy with CIMZIA, all patients must be evaluated for both active and inactive (latent) tuberculosis infection. If active tuberculosis is diagnosed prior to or during treatment, CIMZIA therapy must not be initiated and must be discontinued. If latent tuberculosis is diagnosed, appropriate anti-tuberculosis therapy must be started before initiating treatment with CIMZIA. Patients should be instructed to seek medical advice if signs/symptoms (e.g. persistent cough, wasting/weight loss, low grade fever, listlessness) suggestive of tuberculosis occur during or after therapy with CIMZIA.
Reactivation of hepatitis B has occurred in patients receiving a TNF-antagonist including CIMZIA who are chronic carriers of the virus (i.e. surface antigen positive). Some cases have had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with CIMZIA. Carriers of HBV who require treatment with CIMZIA should be closely monitored and in the case of HBV reactivation CIMZIA should be stopped and effective anti-viral therapy with appropriate supportive treatment should be initiated.
TNF antagonists including CIMZIA may increase the risk of new onset or exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease; of formation of autoantibodies and uncommonly of the development of a lupus-like syndrome; of severe hypersensitivity reactions. If a patient develops any of these adverse reactions, CIMZIA should be discontinued and appropriate therapy instituted.
With the current knowledge, a possible risk for the development of lymphomas, leukaemia or other malignancies in patients treated with a TNF antagonist cannot be excluded. Rare cases of neurological disorders, including seizure disorder, neuritis and peripheral neuropathy, have been reported in patients treated with CIMZIA.
Adverse reactions of the hematologic system, including medically significant cytopaenia, have 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 haematological abnormalities.
The use of CIMZIA in combination with anakinra or abatacept is not recommended due to a potential increased risk of serious infections. As no data are available, CIMZIA should not be administered concurrently with live vaccines. The 14-day half-life of CIMZIA should be taken into consideration if a surgical procedure is planned. A patient who requires surgery while on CIMZIA should be closely monitored for infections.
CIMZIA was studied in 325 patients with active axial spondyloarthritis (axSpA) in a placebo-controlled clinical trial for up to 30 months and in 409 patients with psoriatic arthritis (PsA) in a placebo-controlled clinical trial for up to 30 months. The safety profile for axSpA and PsA patients treated with CIMZIA was consistent with the safety profile in RA and previous experience with CIMZIA.
Please consult the full prescribing information in relation to other side effects, full safety and prescribing information. European SmPC date of revision 27th October 2014.
1. International Federation of Psoriasis Associations. Accessed 27th November 2014 at http://www.worldpsoriasisday.com/web/page.aspx?refid=130
2. CIMZIACIMZIA U.S. Prescribing Information. Accessed 27th November 2014 from http://www.ucb.com/
3. CIMZIACIMZIA EU Summary of Product Characteristics. Accessed 27th November 2014 from http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001037/WC500069763.pdf
Dermira is a biopharmaceutical company dedicated to identifying, developing and commercializing innovative, differentiated therapies to improve the lives of patients with dermatologic diseases. Dermira's portfolio of five product candidates targets significant market opportunities and includes three late-stage product candidates: CIMZIA® (certolizumab pegol), in Phase 3 development in collaboration with UCB Pharma S.A. for the treatment of moderate-to-severe plaque psoriasis; DRM04, in Phase 3 development for the treatment of axillary hyperhidrosis; and DRM01, in Phase 2b development for the treatment of acne. Dermira is headquartered in Menlo Park, California. For more information, please visit www.dermira.com.
The information in this press release contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the "safe harbor" created by those sections. This press release contains forward-looking statements that involve substantial risks and uncertainties, including statements with respect to timing expectations for the receipt and announcement of topline efficacy and safety data from the Phase 3 studies; the desired outcomes of the Phase 3 studies and goal of using certolizumab pegol as an effective treatment for patients with moderate-to-severe plaque psoriasis; and guidelines for interpreting the topline efficacy and safety data from the Phase 3 studies, including expectations regarding necessary achievements to enable registrations in the U.S. and EU. These statements deal with future events and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. Factors that could cause actual results to differ materially include risks and uncertainties such as those relating to the design, implementation and outcomes of our clinical trials; our dependence on third-party clinical research organizations, manufacturers and suppliers; our ability to obtain regulatory approval for our product candidates; and our ability to continue to stay in compliance with applicable laws and regulations. You should refer to the section entitled "Risk Factors" set forth in Dermira's Annual Report on Form 10-K, Dermira's Quarterly Report on Form 10-Q and other filings Dermira makes with the Securities and Exchange Commission from time to time for a discussion of important factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking statements. Furthermore, such forward-looking statements speak only as of the date of this press release. We undertake no obligation to publicly update any forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law.