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

Rhea-AI Summary

Amgen announced positive results from a Phase 3 registrational trial evaluating UPLIZNA® (inebilizumab-cdon) for treating Immunoglobulin G4-related disease (IgG4-RD). The trial, conducted at 80 sites across 22 countries, showed a statistically significant 87% reduction in the risk of IgG4-RD flare compared to placebo, meeting all primary and key secondary endpoints. No new safety signals were identified, and the overall safety profile was consistent with known data. The results mark a significant milestone in treating IgG4-RD, which currently has no approved therapy. Amgen plans to file for approval in the U.S. and other key markets.

Positive

• Statistically significant 87% reduction in IgG4-RD flare risk.
• Primary and all key secondary endpoints met.
• No new safety signals identified.
• First placebo-controlled trial to demonstrate benefit in IgG4-RD.
• Potential for Amgen to file for approval in the U.S. and other key markets.
• Conducted at 80 sites across 22 countries, showcasing broad clinical engagement.

Negative

• No specific financial data or revenue projections from the trial outcomes were provided.
• No immediate impact on stock price indicated from the trial results alone.
• Approval filings and subsequent market entry may face regulatory delays.
• Competition from other therapies in development for IgG4-RD could impact market dynamics.

Insights

Medical Research Analyst

Amgen's announcement of positive results from its Phase 3 trial evaluating UPLIZNA® for the treatment of IgG4-related disease (IgG4-RD) is significant for multiple reasons. Firstly, the data indicating an 87% reduction in disease flares is a remarkable outcome, suggesting that UPLIZNA could become a groundbreaking treatment option for this chronic and often debilitating disease.

The trial's design as a randomized, placebo-controlled study adds robustness to the findings, enhancing the credibility of the results. Meeting both primary and key secondary endpoints provides strong evidence of efficacy, which is critical for future regulatory approval and clinical adoption. Additionally, no new safety signals were identified, which is reassuring for both patients and prescribers.

Given that IgG4-RD currently has no approved therapies, UPLIZNA could fill a significant unmet need, potentially leading to substantial market uptake. The implications for patients are profound, offering a new, effective treatment option that could improve quality of life and disease management. Considering the rarity of IgG4-RD, this development also positions Amgen as a leader in rare disease treatment, a niche but impactful market segment.

Market Research Analyst

From a market perspective, this announcement positions Amgen strongly within the rare diseases sector. The lack of existing approved treatments for IgG4-RD means there is a clear market opportunity with little direct competition. The high efficacy rate demonstrated in the trial (87% reduction in flares) will likely drive both adoption and pricing power, allowing Amgen to potentially set a premium price point for UPLIZNA.

Additionally, Amgen's established expertise and existing approval for UPLIZNA in other conditions, such as Neuromyelitis Optica Spectrum Disorder (NMOSD), may facilitate a smoother regulatory and commercial pathway. Their strategy to file for approval in the U.S. followed by other key markets aligns well with the global unmet need for IgG4-RD treatments.

Considering the rarity of IgG4-RD, peak sales might be limited compared to more common diseases, but the long-term revenue stream from a high-value orphan drug could be substantial. Furthermore, the successful outcome of this trial could enhance Amgen’s reputation in the field of immunology and rare diseases, potentially opening doors for future drug development and partnerships.

Financial Analyst

For investors, the positive Phase 3 trial results for UPLIZNA represent a significant milestone that could enhance Amgen’s financial outlook. High efficacy rates and the potential market exclusivity as the first approved treatment for IgG4-RD can drive substantial revenue growth. This is particularly important given the competitive pressures in Amgen’s broader portfolio and the need for new growth drivers.

Amgen's plan to seek regulatory approval in the U.S. and other major markets suggests a strategic approach to maximize the drug's market potential. Successful approval and commercialization could also bolster Amgen's stock value, given the high-margin nature of orphan drugs. However, investors should also be cognizant of the costs associated with bringing a new drug to market, including regulatory submissions and potential post-marketing studies.

The collaborative support from Mitsubishi Tanabe Pharma and Hansoh Pharma in various regions indicates a well-coordinated effort to penetrate the global market, which can mitigate financial risks and enhance distribution capabilities. Overall, this development is likely to be viewed favorably by the market, with potential for upward movements in Amgen's stock price upon regulatory approvals and market launch.

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

This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd. or Kyowa Kirin Co., Ltd.), the performance of Otezla^® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems on our business, outcomes, progress, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise.

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.

Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

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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FAQ

What were the results of Amgen's Phase 3 trial for UPLIZNA® (AMGN)?

Amgen's Phase 3 trial for UPLIZNA® showed an 87% reduction in IgG4-RD flare risk and met all primary and key secondary endpoints.

When were the results of the UPLIZNA® Phase 3 trial announced?

The results were announced on June 5, 2024.

What is the significance of the Phase 3 trial results for AMGN?

The Phase 3 trial results are significant as they mark the first randomized, placebo-controlled trial to demonstrate benefit in treating IgG4-RD.

Did the UPLIZNA® Phase 3 trial identify any new safety concerns?

No new safety signals were identified in the UPLIZNA® Phase 3 trial.

What are Amgen's plans following the successful UPLIZNA® trial results?

Amgen plans to file for approval in the U.S. and other key markets based on the trial results.

Who conducted the UPLIZNA® Phase 3 trial?

The trial was conducted at 80 sites in 22 countries with the support of Mitsubishi Tanabe Pharma and Hansoh Pharma.

What is the current approval status of UPLIZNA®?

UPLIZNA® is currently approved for Neuromyelitis Optica Spectrum Disorder (NMOSD) by several regulatory bodies, including the U.S. FDA and the European Medicines Agency.

What is IgG4-related disease (IgG4-RD)?

IgG4-RD is a chronic, systemic, immune-mediated, fibroinflammatory disease that can affect multiple organs and currently has no approved therapy.