AMGEN ANNOUNCES POSITIVE RESULTS FOR PHASE 3 REGISTRATIONAL TRIAL EVALUATING UPLIZNA® (INEBILIZUMAB-CDON) FOR TREATMENT OF IMMUNOGLOBULIN G4-RELATED DISEASE (IgG4-RD)

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, Calif., June 5, 2024 /PRNewswire/ — 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.

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 

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

Forward-Looking Statements

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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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The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses.

CONTACT: Amgen, Thousand Oaks

Madison Howard, 773-636-4910 (media)

Elissa Snook, 609-251-1407 (media)

Justin Claeys, 805-313-9775 (investors) 

References

  1. 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.
  2. Stone, J. H., Zen, Y., & Deshpande, V. (2012). IgG4-Related Disease. New England Journal of Medicine, 366(6), 539–551.
  3. 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.
  4. 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.
  5. Zhang, W., & Stone, J. H. (2019). Management of IgG4-related disease. The Lancet Rheumatology, 1(1), e55–e65.
  6. 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.
  7. Wolfson, A. R., & Hamilos, D. L. (2017). Recent advances in understanding and managing IgG4-related disease. F1000Research, 6, 185.

 

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