AMGEN ANNOUNCES POSITIVE RESULTS FOR PHASE 3 REGISTRATIONAL TRIAL EVALUATING UPLIZNA® (INEBILIZUMAB-CDON) FOR TREATMENT OF IMMUNOGLOBULIN G4-RELATED DISEASE (IgG4-RD)
06.05.2024
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Data Show a Statistically Significant 87% Reduction in IgG4-RD Flares, With Primary and All Key Secondary Endpoints Met
First Therapy Proven in a Randomized, Placebo-Controlled Trial to Demonstrate Benefit in IgG4-RD
The trial met its primary endpoint, showing a statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo (
"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
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
UPLIZNA is currently approved for Neuromyelitis Optica Spectrum Disorder (NMOSD) by several regulatory bodies, including the
Based on the MITIGATE primary analysis results, Amgen is planning to file for approval in the
The trial was conducted with the support of
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.
IMPORTANT SAFETY INFORMATION
UPLIZNA is contraindicated in patients with:
- A history of life-threatening infusion reaction to UPLIZNA
- Active hepatitis B infection
- Active or untreated latent tuberculosis
WARNINGS AND PRECAUTIONS
Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine, and an anti-pyretic.
Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%), and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.
Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.
The risk of Hepatitis B Virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.
Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.
Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.
Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.
Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.
Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.
Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.
For additional information on UPLIZNA, please see the Full Prescribing Information at www.UPLIZNA.com.
About Amgen
In 2024,
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Forward-Looking Statements
This news release contains forward-looking statements that are based on the current expectations and beliefs of
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
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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.
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