New Analysis Highlights Importance of Adhering to Uninterrupted Full Course of Treatment with TEPEZZA® (teprotumumab-trbw) to Support Thyroid Eye Disease (TED) Patient Outcomes

-- Additional data presented at ATA 2023 include a subgroup analysis from the TEPEZZA Phase 4 clinical trial and insights on the impact of TED on quality of life (QOL) --

Horizon Therapeutics plc (NASDAQ:HZNP) today announced new data showing that disrupting the recommended TEPEZZA treatment regimen by lengthening the amount of time between infusions can increase the need for a second course of treatment. These findings, along with new subgroup data from the TEPEZZA Phase 4 clinical trial in patients with long disease duration and low Clinical Activity Score (CAS) and an analysis of the impact of TED on QOL, were shared at the 92^nd Annual Meeting of the American Thyroid Association (ATA 2023), Sept. 27-Oct. 1 in Washington, D.C. 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, debilitating and potentially vision-threatening rare autoimmune disease.¹

The FDA-approved dosing schedule for TEPEZZA is one infusion every three weeks for a total of eight IV infusions. An analysis examined whether patients who experience a treatment disruption, defined as a >60-day gap between consecutive infusions, are more likely to need a second course of treatment. Deidentified data of patients prescribed a second course of TEPEZZA after receiving an initial full course were examined for TED-related claims, enrollment for a second course, number of infusions and time between courses. Undisrupted patients (n=4,230) and disrupted patients (n=1,155) were observed for one year after the initial full course of treatment. The majority of treatment disruptions (96%) were related to the short-term TEPEZZA supply disruption that occurred in late 2020 as a result of government-mandated COVID-19 vaccine production orders. Chi-square tests were performed for significance.

The findings revealed that a higher portion of patients who experienced a disruption in their first course of TEPEZZA were prescribed an additional course of treatment compared with those who completed an undisrupted initial course of TEPEZZA (10.5% vs 6.5%; p<0.0001). There was also a difference in claims of proptosis between the groups, with a 5% increase of proptosis among disrupted patients vs a 19% reduction in the undisrupted group pre- to post- treatment with TEPEZZA.²

"This analysis reinforces the importance of adhering to the FDA-approved dosing schedule for TEPEZZA and not lengthening the time between consecutive infusions unless there is a safety concern," said Shoaib Ugradar, MD, private practice, Beverly Hills, CA. "Although treatment delays may result from factors that a prescriber may not directly control, such as changes in insurance coverage or scheduling difficulties, and additional research on this is needed, physicians play an important role in making patients aware that delaying infusions could impact results."

Horizon also announced further results from the TEPEZZA Phase 4 clinical trial in TED patients with long disease duration and low CAS. Findings reinforced a meaningful reduction of proptosis at Week 24 for all subgroups (≥2mm) with comparable improvements regardless of magnitude of baseline proptosis levels (<=25 vs >25mm). Smokers treated with TEPEZZA had a change from baseline (CFB) of -2.83 mm (vs 0.00 CFB for placebo); treated non-smokers had a -2.39 mm CFB (vs -1.00 mm for placebo). Males treated with TEPEZZA (n=10) had a CFB of -2.20 mm (vs -1.00 for placebo, n=2), and in treated females (n=29), CFB was -2.55 mm (vs -0.89 for placebo, n=18).³

Additionally, research on the impact of TED on patients' QOL was presented at ATA 2023, assessing how characteristics like sex, age and severity of symptoms affect visual functioning and appearance as measured by the Graves' Ophthalmopathy Quality of Life (GO-QOL) questionnaire. The analysis looked at baseline GO-QOL data for 171 moderate-to-severe TED patients prior to treatment in two clinical trials. Visual functioning results showed that the majority of participants reported limitations in important daily activities like reading (74%) or driving (64%), and nearly all (95%) were affected by the changes in their appearance. Certain sub-populations noted more significant impact on their daily activities, including those with severe diplopia (n=74) and patients with more proptosis (n=104).⁴

"We are committed to fully understanding the daily challenges that patients with Thyroid Eye Disease experience regardless of their disease activity or duration, including things like symptoms that limit the ability to drive at night, or the mental toll that a lack of independence may bring," said Beth Scott, OD, MS, vice president, medical affairs, Horizon. "The data presented this weekend help us further our mission of ensuring those in the Thyroid Eye Disease community receive appropriate care."

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.

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 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 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. Ugradar S, et al. Disruption of Teprotumumab Treatment in Patients with Thyroid Eye Disease (TED) is Associated with Increased Retreatment Rate. Poster presented at: American Thyroid Association (ATA) Annual Meeting; 2023 Sept 27-Oct 1; Washington, DC.
3. Stan M, et al. Proptosis Improvement in Patients Treated with Teprotumumab in Subgroups from a Randomized, Double-masked, Placebo-controlled Trial of Longer Duration/Low Activity Thyroid Eye Disease. Late-breaker poster presented at: American Thyroid Association (ATA) Annual Meeting; 2023 Sept 27-Oct 1; Washington, DC.
4. Smith TJ, et al. Impact of Thyroid Eye Disease on Specific Activities Measured by the Graves' Quality of Life Questionnaire. Poster presented at: American Thyroid Association (ATA) Annual Meeting; 2023 Sept 27-Oct 1; Washington, DC.
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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