Horizon Therapeutics plc Completes Enrollment for Phase 4 Trial of TEPEZZA® (teprotumumab-trbw) in Adults with Chronic/Low Clinical Activity Score (CAS) Thyroid Eye Disease (TED)

-- Topline results expected in second quarter of 2023 --

Horizon Therapeutics plc (Nasdaq: HZNP) announced that it has completed enrollment of its Phase 4 clinical trial (NCT04583735) evaluating TEPEZZA for the treatment of Thyroid Eye Disease (TED) in patients with a low Clinical Activity Score (CAS), also known as the TEPEZZA Chronic TED trial. CAS is a tool designed to evaluate inflammatory signs and symptoms that are often associated with TED.¹ Topline results are expected in the second quarter of 2023.

TED is a serious, progressive and potentially vision-threatening rare autoimmune disease. Symptoms of TED may include dry eyes and grittiness; redness, swelling and excessive tearing; eyelid retraction; proptosis (eye bulging); pressure and/or pain behind the eyes; and diplopia (double vision). TEPEZZA was approved by the U.S. Food and Drug Administration (FDA) in January 2020 as the first and only medicine for Thyroid Eye Disease.

“I see the severe impact of Thyroid Eye Disease daily in patients with all levels of inflammation, and it disrupts not only their ability to function, but also their enjoyment of life,” said Raymond Douglas, M.D., Ph.D., trial investigator and director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center. “The TEPEZZA pivotal trial data showed significant improvement in some of the most debilitating symptoms of TED in people with more inflammatory disease. Since then, we’ve seen real-world experience and published case reports that have shown benefits of TEPEZZA treatment in patients with low Clinical Activity Scores - this trial will help us better illustrate the use of TEPEZZA in that population.”

This randomized, double-masked, placebo-controlled, parallel-group, multicenter trial is evaluating the efficacy, safety and tolerability of TEPEZZA compared to placebo in treating TED patients with a low CAS (1 or less at the screening and baseline visits), two to 10 years since eye symptom onset, and non-worsening proptosis for at least a year. Adult participants who met the trial eligibility criteria were randomized in a 2:1 ratio to receive an infusion of either TEPEZZA or placebo, 10 mg/kg for the first infusion and 20 mg/kg for the remaining seven infusions, once every three weeks, for a total of eight infusions.

The primary efficacy endpoint is change from baseline at Week 24 in proptosis in the study eye. The trial will also assess proptosis responder rate, diplopia responder rate, change in orbital pain, change in muscle volume and change in the Graves’ Ophthalmopathy Quality of Life (GO-QoL) questionnaire appearance and visual functioning subscales. Proptosis nonresponders who complete the treatment period may choose to enter an open-label extension period where they will receive eight infusions of TEPEZZA.

“We are grateful to the Thyroid Eye Disease patient community and all of our principal investigators for their partnership and participation in this trial,” said Elizabeth H.Z. Thompson, Ph.D., executive vice president, research and development, Horizon. “We frequently hear people with Thyroid Eye Disease stress how the painful, potentially vision-threatening symptoms continue throughout the patient journey. As our understanding of Thyroid Eye Disease and the patient experience continues to evolve, studies like this are critical to ensuring the needs of all patients are being met.”

About Thyroid Eye Disease (TED)

TED is a serious, progressive and potentially vision-threatening rare autoimmune disease.¹ It 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.^2,3 This leads to a cascade of negative effects, which may cause long-term, irreversible damage, including blindness.^4,5 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.

About TEPEZZA

INDICATION

TEPEZZA is indicated for the treatment of Thyroid Eye Disease.

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 managed with medications for glycemic control, if necessary. Monitor patients for elevated blood glucose and symptoms of hyperglycemia while on treatment with TEPEZZA. Patients with preexisting diabetes should be under appropriate glycemic control before 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, and menstrual disorders.

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

About Horizon

Horizon is a global biotechnology company 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, but not limited to, statements related to the potential benefits of TEPEZZA; the anticipated timing of results from the Phase 4 clinical trial; the design of clinical trials and other statements that are not historical facts. These forward-looking statements are based on Horizon’s current expectations and inherently involve significant risks and uncertainties. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties, which include, without limitation, risks related to clinical trials, including the fact that prior results may not predict future clinical trial outcomes; impacts of the COVID-19 pandemic and actions taken to slow its spread, including potential delays in clinical trials; regulatory obligations and oversight, including any changes in the legal and regulatory environment in which Horizon operates and those risks detailed from time-to-time under the caption “Risk Factors” and elsewhere in Horizon’s filings and reports with the SEC. Horizon undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information.

References

1. Barrio-Barrio J, Sabater AL, Bonet-Farriol E, Velazquez-Villoria A, Galofre JC. Graves’ Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmology. 2015;2015:1-16.
2. Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
3. 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.
4. 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.
5. 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. Eur J Endocrinol. 2021;185(4):G43-G67. Published 2021 Aug 27.

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