AMGEN TO SUBMIT TEPROTUMUMAB MARKETING AUTHORIZATION APPLICATION TO THE EUROPEAN MEDICINES AGENCY

THOUSAND OAKS, Calif., April 26, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the imminent submission of a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for teprotumumab, a fully human monoclonal antibody and targeted inhibitor of the insulin-like growth factor-1 receptor (IGF-1R), for the treatment of moderate to severe Thyroid Eye Disease (TED) in adults. TED is a serious, progressive, debilitating and potentially vision-threatening autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling.¹ If approved, teprotumumab would be the first and only medicine approved for TED in the European Union.

"We are enthusiastic to bring a much-needed medicine to the Thyroid Eye Disease community in Europe by leveraging Amgen's strong reputation and broad infrastructure in the region," said Jay Bradner, executive vice president of Research and Development and chief scientific officer at Amgen. "This disease is currently managed with steroids and invasive surgeries, both of which carry their own set of risks. Having access to a non-surgical option like teprotumumab that not only treats the signs and symptoms, but also targets the underlying cause of the disease represents a major advance for patients."

The MAA is supported by multiple well-controlled clinical studies - a Phase 2 clinical study (NCT01868997)¹, Phase 3 confirmatory clinical study OPTIC (NCT03298867)², a Phase 4 study (NCT04583735)³, and a Phase 3 clinical trial in Japan (OPTIC-J, jRCT2031210453) - providing statistically significant and clinically meaningful improvements across multiple facets of TED, including in proptosis and diplopia, among the 287 total patients studied. Additionally, the studies assessed TED signs and symptoms such as pain, inflammation, redness and functional vision. Clinical improvements were seen in proptosis as early as six weeks, with continued improvement across the 24-week treatment period.² Teprotumumab has a well-established safety profile.

"People living with Thyroid Eye Disease, a painful and potentially sight-threatening disease, have no approved treatment options in Europe at this time," said Mario Salvi, MD, founder & head of Graves Orbitopathy Center Aldo, Fondazione IRCCS Ca' Granda, Milano. "When considering the impact of this disease on patients, it's important to look beyond the symptoms, like eye bulging and double vision, and recognize that the inability to work, drive or even look or feel like themselves has a serious negative impact on overall well-being and mental health."  

Teprotumumab is approved for TED in the U.S., Brazil and the Kingdom of Saudi Arabia under the brand name TEPEZZA^®, where it is administered to patients through an intravenous (IV) infusion once every three weeks for a total of eight infusions over the course of about five months.^1,2 

In March 2024, Amgen submitted a marketing authorization application to the Medicines and Healthcare products Regulatory Agency (MHRA) in Great Britain, a New Drug Submission (NDS) to Health Canada and an application to the Therapeutic Goods Administration (TGA) in Australia for teprotumumab. Teprotumumab is also under review by the Ministry of Health, Labour and Welfare (MHLW) in Japan.

About Thyroid Eye Disease (TED)
TED is a serious, progressive, debilitating and potentially vision-threatening autoimmune disease.⁴ It often occurs in people living with Graves' disease, but is a distinct disease that is caused by autoantibodies activating an insulin-like growth factor-1 receptor (IGF-1R)-mediated signaling complex on cells within the retro-orbital space.^5,6 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness.^7,8 Signs and symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis; pressure and/or pain behind the eyes; and diplopia.

About TEPEZZA 

Teprotumumab is marketed as TEPEZZA (teprotumumab-trbw) in the United States. Teprotumumab is not currently approved for commercial use in Europe.

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease regardless of Thyroid Eye Disease activity or duration.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Infusion Reactions: TEPEZZA may cause infusion reactions. Infusion reactions have been reported in approximately 4% of patients treated with TEPEZZA. Reported infusion reactions have usually been mild or moderate in severity. Signs and symptoms may include transient increases in blood pressure, feeling hot, tachycardia, dyspnea, headache, and muscular pain. Infusion reactions may occur during an infusion or within 1.5 hours after an infusion. In patients who experience an infusion reaction, consideration should be given to premedicating with an antihistamine, antipyretic, or corticosteroid and/or administering all subsequent infusions at a slower infusion rate.

Preexisting Inflammatory Bowel Disease: TEPEZZA may cause an exacerbation of preexisting inflammatory bowel disease (IBD). Monitor patients with IBD for flare of disease. If IBD exacerbation is suspected, consider discontinuation of TEPEZZA.

Hyperglycemia: Increased blood glucose or hyperglycemia may occur in patients treated with TEPEZZA. In clinical trials, 10% of patients (two-thirds of whom had preexisting diabetes or impaired glucose tolerance) experienced hyperglycemia. Hyperglycemic events should be controlled with medications for glycemic control, if necessary. Assess patients for elevated blood glucose and symptoms of hyperglycemia prior to infusion and continue to monitor while on treatment with TEPEZZA. Ensure patients with hyperglycemia or preexisting diabetes are under appropriate glycemic control before and while receiving TEPEZZA.

Hearing Impairment Including Hearing Loss: TEPEZZA may cause severe hearing impairment including hearing loss, which in some cases may be permanent. Assess patients' hearing before, during, and after treatment with TEPEZZA and consider the benefit-risk of treatment with patients.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥5% and greater than placebo) are muscle spasm, nausea, alopecia, diarrhea, fatigue, hyperglycemia, hearing impairment, dysgeusia, headache, dry skin, weight decreased, nail disorders, and menstrual disorders.

Please see Full Prescribing Information or visit TEPEZZAhcp.com for more information.

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.  

Amgen 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), the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the Horizon Therapeutics plc acquisition (including the prospective performance and outlook of Horizon's business, performance and opportunities and any potential strategic benefits, synergies or opportunities expected as a result of such acquisition), 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. 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. 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References

1. Smith TJ, Kahaly GJ, Ezra DG, et al. Teprotumumab for thyroid-associated ophthalmopathy. N Engl J Med. 2017;376(18):1748-1761.
2. Douglas RS, Kahaly GJ, Patel A, et al. Teprotumumab for the treatment of active thyroid eye disease. N Engl J Med. 2020;382(4):341-352.
3. Douglas RS, et al. Efficacy and Safety of Teprotumumab in Patients With Thyroid Eye Disease of Long Duration and Low Disease Activity. The Journal of Clinical Endocrinology & Metabolism. 2023; 109 (1): 25-35. 
4. Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
5. Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
6. Pritchard J, et al. Immunoglobulin Activation of T Cell Chemoattractant Expression in Fibroblasts from Patients with Graves' Disease Is Mediated Through the Insulin-Like Growth Factor 1 Receptor Pathway. J Immunol. 2003;170:6348-6354.
7. McKeag D, et al. Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007;91:455-458.
8. Bartalena L, Kahaly GJ, Baldeschi L, et al. The 2021 European Group on Graves' Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves' Orbitopathy [published online ahead of print]. Eur J Endocrinol. 2021 Jul 1:EJE-21-0479.R1. doi: 10.1530/EJE-21-0479.

CONTACT: Amgen, Thousand Oaks
Madison Howard, 773-636-4910 (media)
Jessica Akopyan, 805-440-5721 (media)
Justin Claeys, 805-313-9775 (investors) 

SOURCE Amgen