Horizon Therapeutics plc Announces Positive Topline Data from Phase 3 Clinical Trial (OPTIC-J) in Japan Evaluating TEPEZZA® (teprotumumab-trbw) for the Treatment of Active Thyroid Eye Disease (TED)

-- At Week 24, 89% of patients treated with TEPEZZA had a clinically meaningful improvement in proptosis (≥2 mm) compared with 11% of patients receiving placebo --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced positive topline results from its randomized, double-masked, placebo-controlled Phase 3 clinical trial evaluating TEPEZZA for the treatment of TED in Japanese patients with higher levels of disease activity, as measured by clinical activity score (CAS). TED is a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease that can cause proptosis (eye bulging), diplopia (double vision), eye pain, redness and swelling.¹

“The positive topline results from this trial are important because there are no approved medicines in Japan for Thyroid Eye Disease, resulting in a significant unmet need for patients who are struggling with the physical symptoms of the disease as well as the emotional and social burden that is associated with it,” said Yuji Hiromatsu, M.D., professor emeritus, Kurume University Medical Center and co-coordinating trial investigator. “Currently, the only treatment options in Japan are steroids and multiple invasive surgeries. TEPEZZA would offer patients a non-surgical option that not only treats the symptoms, such as proptosis and diplopia, but targets the underlying mechanism of the disease.”

Topline data demonstrated that the primary endpoint was met. At Week 24, 89% of patients treated with TEPEZZA had a clinically meaningful improvement in proptosis (≥2 mm) compared with placebo (11%) (p<0.0001). The safety profile is consistent with what was observed in previous clinical trials of TEPEZZA. Additional data from the trial will be presented at a medical congress and published in a peer-reviewed medical journal.

“We are thrilled with the results of this trial, and we look forward to working with local investigators and regulators to bring this innovative therapy to patients in Japan who are suffering from Thyroid Eye Disease,” said Elizabeth H.Z. Thompson, Ph.D., executive vice president, research and development, Horizon. “The participation by those living with Thyroid Eye Disease in this clinical trial and the trial investigators was integral in helping us reach this significant milestone.”

A second Phase 3 clinical trial is ongoing in Japan evaluating TEPEZZA for the treatment of adults with chronic TED and low CAS. This trial includes patients with an initial diagnosis of TED between two to 10 years prior to the study and low levels of disease activity.

TEPEZZA was approved by the U.S. Food and Drug Administration (FDA) in January 2020 as the first and only medicine for TED. TEPEZZA has not been approved for commercial use in Japan. There are no medicines approved for the treatment of TED in Japan.

Trial Design

The OPTIC-J trial is a randomized, double-masked, placebo-controlled, parallel-group, multicenter study evaluating the efficacy, tolerability and safety of TEPEZZA in the treatment of patients with moderate-to-severe active TED in Japan. The trial methodology is based on the OPTIC Phase 3 trial conducted in the United States and Europe. Adult participants who met the eligibility criteria were randomized in a 1:1 ratio to receive TEPEZZA (n=27) or placebo (n=27) once every three weeks for a total of eight infusions (10 mg/kg for the first infusion and 20 mg/kg for the remaining seven infusions). All patients were dosed as randomized, and all patients completed the Week 24 assessment.

The primary efficacy endpoint is proptosis response rate at Week 24, measured by 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.

The trial was designed in consultation with Japan’s Pharmaceuticals and Medical Devices Agency (PMDA). More information about the trial is available on the Japan Registry of Clinical Trials website (trial ID number jRCT2031210453).

About Thyroid Eye Disease (TED)

TED is a serious, progressive, debilitating 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

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 managed 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, 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 potential approval and commercial availability of TEPEZZA in Japan; 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. 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 risks regarding whether additional clinical trial results or data analyses will be consistent with preliminary results or results of other trials or Horizon’s expectations, the risks associated with regulatory approvals and adoption of novel medicines, as well as those 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 does not undertake any 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. 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 [published online ahead of print]. Eur J Endocrinol. 2021 Jul 1:EJE-21-0479.R1. doi: 10.1530/EJE-21-0479.

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