Positive top line results from the UCB Phase 2b BE ACTIVE study underscore the potential of bimekizumab to significantly improve joint and skin symptoms in PsA patients
- The study achieved a stringent primary endpoint, with up to 46% of psoriatic arthritis (PsA) patients who received bimekizumab experiencing at least 50% improvement in PsA joint symptoms (ACR50), versus 7% with placebo, at week 12. These results were achieved in a mixed patient population, both biologic naïve and previously biologic exposed patients
- Among patients with active skin lesions (BSA ≥3), up to 65% of patients who received bimekizumab also experienced at least 90% skin clearance (PASI90), a secondary endpoint, versus 7% of patients who received placebo, at week 12
- These data build on the highly positive clinical results recently reported with bimekizumab in psoriasis and ankylosing spondylitis
BRUSSELS, Belgium I December 20, 2017 I UCB today announced that the Phase 2b BE ACTIVE study met the primary objective of establishing dose response for bimekizumab with statistical significance. The study also demonstrated robust efficacy in psoriatic arthritis (PsA) signs and symptoms, as well as skin clearance measured by the PASI90 response, compared to placebo at Week 12.i
“The results observed with bimekizumab are impressive, especially because the study included ACR50 and PASI90, rigorous and meaningful efficacy endpoints. Even at 12 weeks, the results showed strong joint and skin responses, giving PsA patients the possibility of significant disease improvement in two major affected areas where they seek relief,” said Christopher T. Ritchlin, MD, MPH, University of Rochester Medical Center. “A complete and specific blockade of inflammation is key to achieving these compelling results. Preclinical research has shown that dual neutralization of IL-17A and IL-17F inhibits joint and skin inflammation to a greater extent than blocking IL-17A alone. Bimekizumab has the potential to be an important treatment option for PsA patients, many of whom do not respond to or tolerate current therapies.”
“BE ACTIVE confirms a previous proof of concept study in PsA and provides the first Phase 2b clinical efficacy and safety results in PsA with bimekizumab. With the strong results we have seen in psoriasis, ankylosing spondylitis and, now, psoriatic arthritis, UCB is delivering on our Patient Value Strategy to connect unmet patient needs to innovative science. We are committed to rapidly advancing our Phase 3 clinical programs,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President at UCB. “With bimekizumab, we tested the novel hypothesis that neutralizing both IL-17A and IL-17F can deliver superior outcomes for patients with inflammatory diseases. Based on the Phase 2b results in all three disease states, bimekizumab shows potential to bring significant, differentiated value to patients.”
The BE ACTIVE data build on the positive clinical results reported with bimekizumab in both psoriasis and ankylosing spondylitis. In the Phase 2b psoriasis study of moderate-to-severe patients, the dual neutralization of IL-17A and IL-17F with bimekizumab resulted in up to 60% of patients achieving complete skin clearance (PASI100) at week 12.ii A Phase 2b study of bimekizumab in ankylosing spondylitis also achieved the primary endpoint (ASAS40), with up to 47% of patients who received bimekizumab achieving at least 40% improvement in AS symptoms, versus 13% of patients on placebo, at week 12.iii PsA and AS are both forms of spondyloarthritis, a family of pathophysiologically and clinically related rheumatic diseases that typically involve the axial skeleton as well as peripheral joints, and are clearly distinct from rheumatoid arthritis.iv
BE ACTIVE investigated the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of bimekizumab compared with placebo in adult patients with active PsA. The primary efficacy variable evaluated in the Phase 2b BE ACTIVE study was the percentage of PsA patients who achieved at least 50% disease improvement at week 12, as measured by the American College of Rheumatology (ACR50) response. The study had several secondary efficacy variables, including patients who achieved at least 90% psoriatic skin clearance at week 12 (PASI90).v Bimekizumab achieved the primary and secondary clinical response thresholds for a significantly greater number of patients than placebo across multiple doses.i Additionally, bimekizumab was generally well tolerated and no new safety signals were observed. The common cold (nasopharyngitis) was the most frequently reported adverse event compared to placebo.i The BE ACTIVE study will continue for 36 weeks in a dose-blind manner to evaluate maintenance of efficacy and safety.v
About Bimekizumab
Bimekizumab is a novel humanized monoclonal IgG1 antibody that potently and selectively neutralizes both IL-17A and IL-17F, two key cytokines driving inflammatory processes. IL-17A and IL-17F have overlapping pro-inflammatory functions and independently cooperate with other inflammatory mediators to drive chronic inflammation and damage across multiple tissues.
Previous early Phase clinical studies in psoriasis and psoriatic arthritis have suggested that dual neutralization of both IL-17A and IL-17F with bimekizumab may provide a new targeted approach for the treatment of immune-mediated inflammatory diseases.vi,vii Preclinical results in disease-relevant cells have shown that dual neutralization of both IL-17A and IL-17F reduces skin and joint inflammation, as well as pathological bone formation to an extent greater than inhibition of IL-17A or IL-17F alone.vii,viii,ix
UCB is also studying bimekizumab in other disease areas, including psoriasis and ankylosing spondylitis. Bimekizumab is not approved by any regulatory authority worldwide.
About Psoriatic Arthritis (PsA)
PsA is a serious, highly heterogenous, chronic systemic inflammatory condition affecting both the joints and skin, with a prevalence of 0.05% to 0.25% of the population and 6% to 41% of patients with psoriasis.x Symptoms include joint pain and stiffness, skin plaques, swollen toes and fingers, and persistent inflammation of the sites where tendons or ligaments insert into the bone (enthesitis). Up to 40% of people with PsA can suffer from joint destruction and permanent physical deformity.xi,xii
ABOUT BE ACTIVE
BE ACTIVE is a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of bimekizumab compared with placebo in adult patients with PsA. The study included a 12-week double-blind treatment period, after which patients continued to a 36-week dose-blind treatment period. The total duration of treatment is 48 weeks.v
The study included 206 patients with PsA, defined as having symptoms for at least six months prior to
study screening, three or more tender and swollen joint counts ≥ 3 at baseline. Subjects also had to have active psoriatic lesions or a documented history of psoriasis.v
Patients were randomized into five dose regimens to receive either placebo or bimekizumab every four weeks subcutaneously for 12 weeks. They were then re-randomized to a dose-blind bimekizumab treatment group for 36 weeks. Patients are given the option to enter an extension study at week 48.v
The primary efficacy variable evaluated in the Phase 2b BE ACTIVE study in patients with PsA was the percentage of patients who achieved at least 50% disease improvement at week 12, as measured by the ACR50 response. An ACR response is a standard measure of at least a 50% improvement in the number of tender and swollen joints and a 50% improvement in at least three of the following: the patient’s global assessment of disease status; the patient’s global assessment of pain; the physician’s global assessment of disease status; health assessment questionnaire disability index; serum C-reactive protein levels.v
The secondary efficacy variables assessed at week 12 in BE ACTIVE include ACR20 and ACR70, a 20% and 70% improvement, respectively, in the American College of Rheumatology criteria; PASI90 and PASI75, a 90% and 75% improvement, respectively, in the Psoriasis Area and Severity Index. Safety variables include incidence of adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs and change from baseline in clinical laboratory variables.v
About UCB
UCB, Brussels, Belgium (www.ucb.com) 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 7,500 people in approximately 40 countries, the company generated revenue of € 4.2 billion in 2016. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news
i UCB Data on File. December 2017.
ii UCB Data on File. July 2017.
iii UCB Data on File. December 2017.
iv American College of Rheumatology. Spondyloarthritis. Accessed at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis. November 27, 2017.
v UCB Clinical Study Protocol. PROTOCOL PA0008 AMENDMENT 1. 16th December 2016.
vi Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017 May;83(5):991-1001. doi: 10.1111/bcp.13185. Epub 2017 Jan 10.
vii Glatt S, Baeten D, Baker T, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomized placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. In Press.
viii Shah M, Maroof A, Al-Hosni R, Gikas P, Gozzard N, Shaw S, Roberts S. Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10).
UCB Data on File. July 2017.
ix Maroof A, Okoye R, Smallie T, et al. Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells. Ann Rheum Dis. 201706;76 (suppl.2):213-213.
x Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. 2015 November; 41(4): 545–568. doi:10.1016/j.rdc.2015.07.001.
xi Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014; 74:423-441.
xii Hammadi A. Psoriatic arthritis: prognosis. Medscape, December 11, 2014. Available at http://emedicine.medscape.com/article/2196539-overview#a6. Last accessed October 26, 2015.
SOURCE: UCB
Post Views: 23
Positive top line results from the UCB Phase 2b BE ACTIVE study underscore the potential of bimekizumab to significantly improve joint and skin symptoms in PsA patients
- The study achieved a stringent primary endpoint, with up to 46% of psoriatic arthritis (PsA) patients who received bimekizumab experiencing at least 50% improvement in PsA joint symptoms (ACR50), versus 7% with placebo, at week 12. These results were achieved in a mixed patient population, both biologic naïve and previously biologic exposed patients
- Among patients with active skin lesions (BSA ≥3), up to 65% of patients who received bimekizumab also experienced at least 90% skin clearance (PASI90), a secondary endpoint, versus 7% of patients who received placebo, at week 12
- These data build on the highly positive clinical results recently reported with bimekizumab in psoriasis and ankylosing spondylitis
BRUSSELS, Belgium I December 20, 2017 I UCB today announced that the Phase 2b BE ACTIVE study met the primary objective of establishing dose response for bimekizumab with statistical significance. The study also demonstrated robust efficacy in psoriatic arthritis (PsA) signs and symptoms, as well as skin clearance measured by the PASI90 response, compared to placebo at Week 12.i
“The results observed with bimekizumab are impressive, especially because the study included ACR50 and PASI90, rigorous and meaningful efficacy endpoints. Even at 12 weeks, the results showed strong joint and skin responses, giving PsA patients the possibility of significant disease improvement in two major affected areas where they seek relief,” said Christopher T. Ritchlin, MD, MPH, University of Rochester Medical Center. “A complete and specific blockade of inflammation is key to achieving these compelling results. Preclinical research has shown that dual neutralization of IL-17A and IL-17F inhibits joint and skin inflammation to a greater extent than blocking IL-17A alone. Bimekizumab has the potential to be an important treatment option for PsA patients, many of whom do not respond to or tolerate current therapies.”
“BE ACTIVE confirms a previous proof of concept study in PsA and provides the first Phase 2b clinical efficacy and safety results in PsA with bimekizumab. With the strong results we have seen in psoriasis, ankylosing spondylitis and, now, psoriatic arthritis, UCB is delivering on our Patient Value Strategy to connect unmet patient needs to innovative science. We are committed to rapidly advancing our Phase 3 clinical programs,” said Emmanuel Caeymaex, Head of Immunology and Executive Vice President at UCB. “With bimekizumab, we tested the novel hypothesis that neutralizing both IL-17A and IL-17F can deliver superior outcomes for patients with inflammatory diseases. Based on the Phase 2b results in all three disease states, bimekizumab shows potential to bring significant, differentiated value to patients.”
The BE ACTIVE data build on the positive clinical results reported with bimekizumab in both psoriasis and ankylosing spondylitis. In the Phase 2b psoriasis study of moderate-to-severe patients, the dual neutralization of IL-17A and IL-17F with bimekizumab resulted in up to 60% of patients achieving complete skin clearance (PASI100) at week 12.ii A Phase 2b study of bimekizumab in ankylosing spondylitis also achieved the primary endpoint (ASAS40), with up to 47% of patients who received bimekizumab achieving at least 40% improvement in AS symptoms, versus 13% of patients on placebo, at week 12.iii PsA and AS are both forms of spondyloarthritis, a family of pathophysiologically and clinically related rheumatic diseases that typically involve the axial skeleton as well as peripheral joints, and are clearly distinct from rheumatoid arthritis.iv
BE ACTIVE investigated the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics (PD) of bimekizumab compared with placebo in adult patients with active PsA. The primary efficacy variable evaluated in the Phase 2b BE ACTIVE study was the percentage of PsA patients who achieved at least 50% disease improvement at week 12, as measured by the American College of Rheumatology (ACR50) response. The study had several secondary efficacy variables, including patients who achieved at least 90% psoriatic skin clearance at week 12 (PASI90).v Bimekizumab achieved the primary and secondary clinical response thresholds for a significantly greater number of patients than placebo across multiple doses.i Additionally, bimekizumab was generally well tolerated and no new safety signals were observed. The common cold (nasopharyngitis) was the most frequently reported adverse event compared to placebo.i The BE ACTIVE study will continue for 36 weeks in a dose-blind manner to evaluate maintenance of efficacy and safety.v
About Bimekizumab
Bimekizumab is a novel humanized monoclonal IgG1 antibody that potently and selectively neutralizes both IL-17A and IL-17F, two key cytokines driving inflammatory processes. IL-17A and IL-17F have overlapping pro-inflammatory functions and independently cooperate with other inflammatory mediators to drive chronic inflammation and damage across multiple tissues.
Previous early Phase clinical studies in psoriasis and psoriatic arthritis have suggested that dual neutralization of both IL-17A and IL-17F with bimekizumab may provide a new targeted approach for the treatment of immune-mediated inflammatory diseases.vi,vii Preclinical results in disease-relevant cells have shown that dual neutralization of both IL-17A and IL-17F reduces skin and joint inflammation, as well as pathological bone formation to an extent greater than inhibition of IL-17A or IL-17F alone.vii,viii,ix
UCB is also studying bimekizumab in other disease areas, including psoriasis and ankylosing spondylitis. Bimekizumab is not approved by any regulatory authority worldwide.
About Psoriatic Arthritis (PsA)
PsA is a serious, highly heterogenous, chronic systemic inflammatory condition affecting both the joints and skin, with a prevalence of 0.05% to 0.25% of the population and 6% to 41% of patients with psoriasis.x Symptoms include joint pain and stiffness, skin plaques, swollen toes and fingers, and persistent inflammation of the sites where tendons or ligaments insert into the bone (enthesitis). Up to 40% of people with PsA can suffer from joint destruction and permanent physical deformity.xi,xii
ABOUT BE ACTIVE
BE ACTIVE is a multi-center, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study of bimekizumab compared with placebo in adult patients with PsA. The study included a 12-week double-blind treatment period, after which patients continued to a 36-week dose-blind treatment period. The total duration of treatment is 48 weeks.v
The study included 206 patients with PsA, defined as having symptoms for at least six months prior to
study screening, three or more tender and swollen joint counts ≥ 3 at baseline. Subjects also had to have active psoriatic lesions or a documented history of psoriasis.v
Patients were randomized into five dose regimens to receive either placebo or bimekizumab every four weeks subcutaneously for 12 weeks. They were then re-randomized to a dose-blind bimekizumab treatment group for 36 weeks. Patients are given the option to enter an extension study at week 48.v
The primary efficacy variable evaluated in the Phase 2b BE ACTIVE study in patients with PsA was the percentage of patients who achieved at least 50% disease improvement at week 12, as measured by the ACR50 response. An ACR response is a standard measure of at least a 50% improvement in the number of tender and swollen joints and a 50% improvement in at least three of the following: the patient’s global assessment of disease status; the patient’s global assessment of pain; the physician’s global assessment of disease status; health assessment questionnaire disability index; serum C-reactive protein levels.v
The secondary efficacy variables assessed at week 12 in BE ACTIVE include ACR20 and ACR70, a 20% and 70% improvement, respectively, in the American College of Rheumatology criteria; PASI90 and PASI75, a 90% and 75% improvement, respectively, in the Psoriasis Area and Severity Index. Safety variables include incidence of adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs and change from baseline in clinical laboratory variables.v
About UCB
UCB, Brussels, Belgium (www.ucb.com) 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 7,500 people in approximately 40 countries, the company generated revenue of € 4.2 billion in 2016. UCB is listed on Euronext Brussels (symbol: UCB). Follow us on Twitter: @UCB_news
i UCB Data on File. December 2017.
ii UCB Data on File. July 2017.
iii UCB Data on File. December 2017.
iv American College of Rheumatology. Spondyloarthritis. Accessed at: https://www.rheumatology.org/I-Am-A/Patient-Caregiver/Diseases-Conditions/Spondyloarthritis. November 27, 2017.
v UCB Clinical Study Protocol. PROTOCOL PA0008 AMENDMENT 1. 16th December 2016.
vi Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017 May;83(5):991-1001. doi: 10.1111/bcp.13185. Epub 2017 Jan 10.
vii Glatt S, Baeten D, Baker T, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomized placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. In Press.
viii Shah M, Maroof A, Al-Hosni R, Gikas P, Gozzard N, Shaw S, Roberts S. Bimekizumab Blocks T Cell-Mediated Osteogenic Differentiation of Periosteal Stem Cells: Coupling Pathological Bone Formation to IL-17A and IL-17F Signaling [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10).
UCB Data on File. July 2017.
ix Maroof A, Okoye R, Smallie T, et al. Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells. Ann Rheum Dis. 201706;76 (suppl.2):213-213.
x Ogdie A, Weiss P. The Epidemiology of Psoriatic Arthritis. Rheum Dis Clin North Am. 2015 November; 41(4): 545–568. doi:10.1016/j.rdc.2015.07.001.
xi Mease PJ, Armstrong AW. Managing patients with psoriatic disease: the diagnosis and pharmacologic treatment of psoriatic arthritis in patients with psoriasis. Drugs. 2014; 74:423-441.
xii Hammadi A. Psoriatic arthritis: prognosis. Medscape, December 11, 2014. Available at http://emedicine.medscape.com/article/2196539-overview#a6. Last accessed October 26, 2015.
SOURCE: UCB
Post Views: 23
