Horizon Therapeutics plc Announces Initiation of Phase 3 Clinical Trial in Japan Evaluating TEPEZZA® (teprotumumab-trbw) in Adults with Chronic/Low Clinical Activity Score (CAS) Thyroid Eye Disease (TED)

DUBLIN--(BUSINESS WIRE)--Horizon Therapeutics plc (Nasdaq: HZNP) today announced that the first patient has been enrolled in a Phase 3 clinical trial in Japan evaluating TEPEZZA for the treatment of adults with chronic Thyroid Eye Disease (TED) and low clinical activity score (CAS), which is a measure of disease activity. The trial includes patients with an initial diagnosis of TED between two to 10 years prior to the study and low levels of disease activity. Findings from this study will build on a separate Phase 3 clinical trial (OPTIC-J) that is currently underway in Japan and is evaluating TEPEZZA for the treatment of TED patients with disease duration of nine months or less and higher levels of disease activity.

TED is a serious, progressive and potentially vision-threatening rare autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling.¹ TEPEZZA was approved by the U.S. Food and Drug Administration (FDA) in January 2020 and is the first and only medicine for TED, regardless of TED activity or duration. TEPEZZA has not been approved for commercial use in Japan. There are no medicines approved for the treatment of TED in Japan.

This randomized, double-masked, placebo-controlled, parallel-group, multicenter trial will be evaluating the efficacy, safety and tolerability of TEPEZZA compared to placebo in adults with chronic TED and low CAS. All study participants will be required to have a CAS of ≤2 at the screening and baseline visits, two to 10 years since initial diagnosis of TED, and no worsening in proptosis, diplopia or inflammatory symptoms of TED for at least one year. Adult participants who meet the trial eligibility criteria will be 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 proptosis response rate at Week 24, defined as the percentage of participants with at least a 2 mm reduction in proptosis from baseline in the study eye, without deterioration in the fellow eye (≥ 2 mm increase). Study participants who complete the treatment period and are proptosis non-responders at Week 24 may choose to enter an open-label extension period to receive an additional eight infusions of TEPEZZA.

“We know that patients who have lived with Thyroid Eye Disease for quite some time may continue to experience debilitating symptoms that impact their day to day lives and activities,” said Elizabeth H.Z. Thompson, Ph.D., executive vice president, research and development, Horizon. “Therefore, it’s important that we explore the efficacy of TEPEZZA in those with more chronic disease. We are grateful to have the opportunity to work with local researchers, regulators and patients on this trial to accomplish that goal.”

The trial was designed in consultation with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). More information about the trial, including eligibility criteria, is available on the Japan Registry of Clinical Trials website (trial ID number jRCT2031220730).

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 insulin-like growth factor-1 receptor (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

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

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 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 regarding the potential benefits of TEPEZZA as a treatment of TED; the expected scope and 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 potential delays in completing clinical trials and the fact that prior results may not predict future clinical trial outcomes; risks related to regulatory approvals; impacts of the COVID-19 pandemic and actions taken to slow its spread; 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, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
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.

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