Data Show a Statistically Significant 87% Reduction in IgG4-RD Flares, With Primary and All Key Secondary Endpoints Met
First Randomized, Placebo-Controlled Trial to Demonstrate Benefit in IgG4-RD
THOUSAND OAKS, CA, USA I June 5, 2024 I Amgen (NASDAQ:AMGN) today announced positive topline results from its randomized, double-blind, multicenter, placebo-controlled Phase 3 clinical trial (NCT04540497) evaluating the efficacy and safety of UPLIZNA® (inebilizumab-cdon) for the treatment of Immunoglobulin G4-related disease (IgG4-RD).
The trial met its primary endpoint, showing a statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.13, p<0.0001) during the 52-week placebo-controlled period. All key secondary endpoints were also met, which were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission. No new safety signals were identified. The overall safety results during the placebo-controlled period of the trial were consistent with the known safety profile of UPLIZNA. Full data from the trial will be presented at a future medical meeting.
“MITIGATE is a landmark study with results that demonstrate an important advance in the treatment of patients with IgG4-RD, a devastating and rare disease that currently has no approved therapy,” said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. “We are grateful for the partnership with patients, clinicians and patient advocacy groups critical to a successful study, and we look forward to bringing this therapy to those living with IgG4-RD.”
MITIGATE was conducted at 80 sites in 22 countries. It is the first placebo-controlled trial providing class 1 evidence for treating IgG4-RD, a chronic, systemic, immune-mediated, fibroinflammatory disease that can affect almost any organ in the body, often involving multiple organs at a time, and can result in irreversible organ damage. The novel, steroid-sparing study design paves the way for a reduced toxicity treatment approach.
“IgG4-RD is a devastating, chronic, immune-mediated disease that has just begun to be fully understood over the last few decades,” said John Stone, M.D., M.P.H., principal investigator, and a professor of medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital. “These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD, but also key insights into the nature of this condition.”
UPLIZNA is currently approved for Neuromyelitis Optica Spectrum Disorder (NMOSD) by several regulatory bodies, including the U.S. Food and Drug Administration, the European Medicines Agency, Health Canada and the Brazilian Health Regulatory Agency (ANVISA), among others.
Based on the MITIGATE primary analysis results, Amgen is planning to file for approval in the U.S. followed by other key markets.
The trial was conducted with the support of Mitsubishi Tanabe Pharma and Hansoh Pharma. Mitsubishi Tanabe Pharma holds marketing authorization for UPLIZNA in Japan, Thailand, South Korea, Indonesia, Vietnam, Malaysia, Philippines, Singapore, and Taiwan. Hansoh Pharma is the exclusive licensee, local regulatory and commercial agent for China’s mainland, Hong Kong, and Macau.
About the MITIGATE Trial
MITIGATE is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial designed to evaluate the efficacy and safety of UPLIZNA compared to placebo in reducing the risk of flares in adults with IgG4-RD.
The trial enrolled 135 adults with IgG4-RD who met a robust assessment and central eligibility review. Eligibility criteria included multi-organ disease history and active disease being treated with glucocorticoids at the time of screening to ensure enrollment of a patient population at risk of flares for the primary endpoint.
After a screening period of up to 28 days, patients were randomized (1:1) to receive 300 mg intravenous (IV) UPLIZNA or placebo on Days 1, 15, and Week 26 after premedication, and followed for the 52-week randomized control period.
The primary endpoint was time to first treated and adjudicated IgG4-RD flare. The three key secondary endpoints were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission. The MITIGATE trial also includes an optional 3-year open-label treatment period and a safety follow-up period after UPLIZNA discontinuation of up to two years.
About Immunoglobulin G4-related disease (IgG4-RD)
Immunoglobulin G4-related disease (IgG4-RD) is a chronic, systemic, immune-mediated, fibroinflammatory disease which can affect numerous and generally multiple organs of the body.1,2 It is a progressive disease affecting new organs over time either consecutively or simultaneously and is characterized by periods of remission and unpredictable disease flares.3,4 IgG4-RD can cause irreversible organ damage with or without the presence of symptoms.5 B cells are central to the pathogenesis of IgG4-RD.1 In IgG4-RD, CD19-expressing (CD19+) B cells are thought to drive inflammatory and fibrotic processes and interact with other immune cells that contribute to disease activity.1,2,7
The incidence is estimated at 1-5 in 100,000 although the number of IgG4-RD patients is difficult to determine based on limited epidemiology data.3 The typical age of onset of IgG4-RD is between 50 and 70 years old4 and, unlike many other immune-mediated diseases, IgG4-RD is more likely to occur in men than women.6
About UPLIZNA® (inebilizumab-cdon)
INDICATION
UPLIZNA® (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
For additional information on UPLIZNA, please see the Full Prescribing Information at www.UPLIZNA.com.
About Amgen
Amgen discovers, develops, manufactures, and delivers innovative medicines to help millions of patients in their fight against some of the world’s toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what’s known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the “World’s Most Innovative Companies” by Fast Company and one of “America’s Best Large Employers” by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.
References
- Perugino, C. A., & Stone, J. H. (2020). IgG4-related disease: an update on pathophysiology and implications for clinical care. Nature Reviews Rheumatology, 16(12), 702–714.
- Stone, J. H., Zen, Y., & Deshpande, V. (2012). IgG4-Related Disease. New England Journal of Medicine, 366(6), 539–551.
- Floreani, A., Okazaki, K., Uchida, K., & Gershwin, M. E. (2021). IgG4-related disease: Changing epidemiology and new thoughts on a multisystem disease. Journal of Translational Autoimmunity, 4, 100074.
- Wallace, Z. S., Mattoo, H., Mahajan, V. S., Kulikova, M., Lu, L., Deshpande, V., Choi, H. K., Pillai, S., & Stone, J. H. (2016). Predictors of disease relapse in IgG4-related disease following rituximab. Rheumatology, 55(6), 1000–1008.
- Zhang, W., & Stone, J. H. (2019). Management of IgG4-related disease. The Lancet Rheumatology, 1(1), e55–e65.
- Brito-Zerón, P., Bosch, X., Gandía, M., Soto Cárdenas, M.-J. , Ramos-Casals, M., & Stone, J. H. (2017, January 1). Chapter 22 (pages 399-410) – IgG4-Related Disease: Gastrointestinal Involvement (M. Ramos-Casals, M. Khamashta, P. Britó-Zeron, F. Atzeni, & J. R. Teixidor, Eds.). ScienceDirect; Elsevier.
- Wolfson, A. R., & Hamilos, D. L. (2017). Recent advances in understanding and managing IgG4-related disease. F1000Research, 6, 185.
SOURCE: Amgen
Post Views: 1,568
Data Show a Statistically Significant 87% Reduction in IgG4-RD Flares, With Primary and All Key Secondary Endpoints Met
First Randomized, Placebo-Controlled Trial to Demonstrate Benefit in IgG4-RD
THOUSAND OAKS, CA, USA I June 5, 2024 I Amgen (NASDAQ:AMGN) today announced positive topline results from its randomized, double-blind, multicenter, placebo-controlled Phase 3 clinical trial (NCT04540497) evaluating the efficacy and safety of UPLIZNA® (inebilizumab-cdon) for the treatment of Immunoglobulin G4-related disease (IgG4-RD).
The trial met its primary endpoint, showing a statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.13, p<0.0001) during the 52-week placebo-controlled period. All key secondary endpoints were also met, which were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission. No new safety signals were identified. The overall safety results during the placebo-controlled period of the trial were consistent with the known safety profile of UPLIZNA. Full data from the trial will be presented at a future medical meeting.
“MITIGATE is a landmark study with results that demonstrate an important advance in the treatment of patients with IgG4-RD, a devastating and rare disease that currently has no approved therapy,” said Jay Bradner, M.D., executive vice president, Research and Development, and chief scientific officer at Amgen. “We are grateful for the partnership with patients, clinicians and patient advocacy groups critical to a successful study, and we look forward to bringing this therapy to those living with IgG4-RD.”
MITIGATE was conducted at 80 sites in 22 countries. It is the first placebo-controlled trial providing class 1 evidence for treating IgG4-RD, a chronic, systemic, immune-mediated, fibroinflammatory disease that can affect almost any organ in the body, often involving multiple organs at a time, and can result in irreversible organ damage. The novel, steroid-sparing study design paves the way for a reduced toxicity treatment approach.
“IgG4-RD is a devastating, chronic, immune-mediated disease that has just begun to be fully understood over the last few decades,” said John Stone, M.D., M.P.H., principal investigator, and a professor of medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at the Massachusetts General Hospital. “These data mark a major milestone for the IgG4-RD community and provide substantial insight into not only how inebilizumab can help manage IgG4-RD, but also key insights into the nature of this condition.”
UPLIZNA is currently approved for Neuromyelitis Optica Spectrum Disorder (NMOSD) by several regulatory bodies, including the U.S. Food and Drug Administration, the European Medicines Agency, Health Canada and the Brazilian Health Regulatory Agency (ANVISA), among others.
Based on the MITIGATE primary analysis results, Amgen is planning to file for approval in the U.S. followed by other key markets.
The trial was conducted with the support of Mitsubishi Tanabe Pharma and Hansoh Pharma. Mitsubishi Tanabe Pharma holds marketing authorization for UPLIZNA in Japan, Thailand, South Korea, Indonesia, Vietnam, Malaysia, Philippines, Singapore, and Taiwan. Hansoh Pharma is the exclusive licensee, local regulatory and commercial agent for China’s mainland, Hong Kong, and Macau.
About the MITIGATE Trial
MITIGATE is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial designed to evaluate the efficacy and safety of UPLIZNA compared to placebo in reducing the risk of flares in adults with IgG4-RD.
The trial enrolled 135 adults with IgG4-RD who met a robust assessment and central eligibility review. Eligibility criteria included multi-organ disease history and active disease being treated with glucocorticoids at the time of screening to ensure enrollment of a patient population at risk of flares for the primary endpoint.
After a screening period of up to 28 days, patients were randomized (1:1) to receive 300 mg intravenous (IV) UPLIZNA or placebo on Days 1, 15, and Week 26 after premedication, and followed for the 52-week randomized control period.
The primary endpoint was time to first treated and adjudicated IgG4-RD flare. The three key secondary endpoints were annualized flare rate; flare-free, treatment-free complete remission; and flare-free, corticosteroid-free complete remission. The MITIGATE trial also includes an optional 3-year open-label treatment period and a safety follow-up period after UPLIZNA discontinuation of up to two years.
About Immunoglobulin G4-related disease (IgG4-RD)
Immunoglobulin G4-related disease (IgG4-RD) is a chronic, systemic, immune-mediated, fibroinflammatory disease which can affect numerous and generally multiple organs of the body.1,2 It is a progressive disease affecting new organs over time either consecutively or simultaneously and is characterized by periods of remission and unpredictable disease flares.3,4 IgG4-RD can cause irreversible organ damage with or without the presence of symptoms.5 B cells are central to the pathogenesis of IgG4-RD.1 In IgG4-RD, CD19-expressing (CD19+) B cells are thought to drive inflammatory and fibrotic processes and interact with other immune cells that contribute to disease activity.1,2,7
The incidence is estimated at 1-5 in 100,000 although the number of IgG4-RD patients is difficult to determine based on limited epidemiology data.3 The typical age of onset of IgG4-RD is between 50 and 70 years old4 and, unlike many other immune-mediated diseases, IgG4-RD is more likely to occur in men than women.6
About UPLIZNA® (inebilizumab-cdon)
INDICATION
UPLIZNA® (inebilizumab-cdon) is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.
For additional information on UPLIZNA, please see the Full Prescribing Information at www.UPLIZNA.com.
About Amgen
Amgen discovers, develops, manufactures, and delivers innovative medicines to help millions of patients in their fight against some of the world’s toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what’s known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.
In 2024, Amgen was named one of the “World’s Most Innovative Companies” by Fast Company and one of “America’s Best Large Employers” by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average®, and it is also part of the Nasdaq-100 Index®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.
For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.
References
- Perugino, C. A., & Stone, J. H. (2020). IgG4-related disease: an update on pathophysiology and implications for clinical care. Nature Reviews Rheumatology, 16(12), 702–714.
- Stone, J. H., Zen, Y., & Deshpande, V. (2012). IgG4-Related Disease. New England Journal of Medicine, 366(6), 539–551.
- Floreani, A., Okazaki, K., Uchida, K., & Gershwin, M. E. (2021). IgG4-related disease: Changing epidemiology and new thoughts on a multisystem disease. Journal of Translational Autoimmunity, 4, 100074.
- Wallace, Z. S., Mattoo, H., Mahajan, V. S., Kulikova, M., Lu, L., Deshpande, V., Choi, H. K., Pillai, S., & Stone, J. H. (2016). Predictors of disease relapse in IgG4-related disease following rituximab. Rheumatology, 55(6), 1000–1008.
- Zhang, W., & Stone, J. H. (2019). Management of IgG4-related disease. The Lancet Rheumatology, 1(1), e55–e65.
- Brito-Zerón, P., Bosch, X., Gandía, M., Soto Cárdenas, M.-J. , Ramos-Casals, M., & Stone, J. H. (2017, January 1). Chapter 22 (pages 399-410) – IgG4-Related Disease: Gastrointestinal Involvement (M. Ramos-Casals, M. Khamashta, P. Britó-Zeron, F. Atzeni, & J. R. Teixidor, Eds.). ScienceDirect; Elsevier.
- Wolfson, A. R., & Hamilos, D. L. (2017). Recent advances in understanding and managing IgG4-related disease. F1000Research, 6, 185.
SOURCE: Amgen
Post Views: 1,568
