Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of a series of analyses demonstrating the risk of hearing-related events among people with Graves’ disease and TED, including among those treated with TEPEZZA. TEPEZZA is the first and only medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of TED, regardless of disease activity or duration. TED is a serious, progressive and potentially vision-threatening rare autoimmune disease.¹

Data presented at the American Association of Clinical Endocrinology Annual Meeting (AACE 2023) in May shared further information on hearing-related adverse events (AEs) in the TEPEZZA pivotal trials. Results from two studies shared at the Endocrine Society Annual Meeting (ENDO 2023) today assessed hearing-related AEs in populations with Graves’ disease and TED, as well as in a dataset from eight oncology trials for teprotumumab.

Graves’ Disease and TED Linked to Hearing Loss

Decreased hearing, particularly at high frequencies, has been observed in people with Graves’ disease, but specific prevalence data among the population with TED is limited. An analysis presented at ENDO (P81, TJ Smith) assessed data on hearing-related medical claims among people with Graves’ disease, TED and those who received TEPEZZA treatment. Evidence of increased hearing-related issues in people who live with Graves’ disease and TED, irrespective of treatment with TEPEZZA, was uncovered, supporting the need to evaluate hearing-related medical history in people with thyroid autoimmunity, especially when considering treatment options.²

“The robust patient experience, made available through these medical claims-based analyses, has helped illustrate the correlation between thyroid autoimmunity and hearing-related challenges. The analyses highlight the need for screening and evaluation of this patient community,” said Dr. Terry Smith, study author and Professor Emeritus at the Department of Ophthalmology and Visual Sciences, W.K. Kellogg Eye Center, University of Michigan Medical School. “While we continue to study the risk of hearing-related events associated with TEPEZZA, these data further reinforce its strong clinical profile in treating people with Thyroid Eye Disease.”

Quality of Life (QOL) for Those with Hearing-Related Events Improved During TEPEZZA Trials

A further look at hearing-related AEs in the TEPEZZA Phase 2 and 3 pivotal trials and the Phase 3 open-label study was shared last month at AACE and published in Endocrine Practice evaluating Graves’ Ophthalmopathy Quality of Life (GO-QOL) scores among the 12 trial participants who reported tinnitus, hearing impairment or dysfunction compared to those without hearing-related events (n=109). The baseline overall GO-QOL score was similar between those with and without hearing-related AEs (61 and 63, respectively). Mean overall GO-QOL scores improved significantly for both groups from baseline throughout the trials, and by Week 24, each participant who reported a hearing AE experienced improvements in their GO-QOL score from baseline and none of the patients withdrew from the study.³

Hearing-Related Events in TEPEZZA TED Trials Consistent with Large Historical Cancer Trials

Prior to the FDA approval of TEPEZZA for TED, teprotumumab was evaluated as a potential cancer therapeutic. In clinical trials, hearing-related AEs with insulin-like growth factor-I receptor inhibitors have been reported. This analysis presented at ENDO (P81, TJ Smith) reviewed reports of hearing-related events in eight oncology trials where teprotumumab was administered either as a monotherapy (n=362) or in combination with other cancer therapies (n=271). The evaluation found consistent types of hearing-related events with similar incidence as reported in TED trials and in the FDA-approved labeling for TEPEZZA.⁴

“We are committed to research that helps us better understand the physically devastating and emotionally burdensome impact of Thyroid Eye Disease and supports a positive treatment experience while establishing a positive benefit/risk profile,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, chief medical officer, Horizon. “Before TEPEZZA, there was a significant unmet need for an effective medicine to treat Thyroid Eye Disease. We will continue to advance the science of Thyroid Eye Disease with the patient voice at the forefront of all we do.”

About Thyroid Eye Disease (TED)

TED is a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease.¹ TED often occurs in people living with Graves’ disease, but is a distinct disease that is caused by autoantibodies activating an 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. Early 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.^7,8

About TEPEZZA

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.

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 Horizon

Horizon is focused on the discovery, development and commercialization of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases. Our pipeline is purposeful: We apply scientific expertise and courage to bring clinically meaningful therapies to patients. We believe science and compassion must work together to transform lives. For more information on how we go to incredible lengths to impact lives, visit www.horizontherapeutics.com and follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking Statements

This press release contains forward-looking statements, including statements regarding potential benefits of TEPEZZA in treating Thyroid Eye Disease and Horizon’s future clinical research plans. These forward-looking statements are based on management’s expectations and assumptions as of the date of this press release and actual results may differ materially from those in these forward-looking statements as a result of various factors. These factors include, but are not limited to, risks regarding whether future data analyses or clinical trial results will be consistent with prior clinical trials or Horizon’s expectations. For a further description of these and other risks facing Horizon, please see the risk factors described in Horizon’s filings with the United States Securities and Exchange Commission, including those factors discussed under the caption “Risk Factors” in those filings. Forward-looking statements speak only as of the date of this press release and Horizon undertakes no obligation to update or revise these statements, except as may be required by law.

References

1. Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
2. Smith TJ, et al. Hearing-related Issues Associated with Graves’ Disease, Thyroid Eye Disease and Treatment with Teprotumumab. Poster session presented at: Endocrine Society (ENDO) Annual Meeting; 2023 June 15-18; Chicago, IL.
3. Smith TJ, et al. Hearing-Related Adverse Events and Quality of Life Assessments in Thyroid Eye Disease Patients Treated with Teprotumumab. Endocrine Practice. 2023;29:S110.
4. Smith TJ, et al. Hearing-Related Adverse Events in Teprotumumab Oncology Clinical Trials. Poster session presented at: Endocrine Society (ENDO) Annual Meeting; 2023 June 15-18; Chicago, IL.
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. Bartalena L, et al. The 2021 European Group on Graves’ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves’ Orbitopathy. Eur J Endocrinol. 2021;185:G43–G67.
8. 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.

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