-- Data at Week 24 show 2.41 mm reduction in proptosis in patients treated with TEPEZZA compared with 0.92 mm in those who received placebo; 62% of TEPEZZA patients had clinically meaningful improvement in proptosis (≥2 mm) compared with 25% of placebo patients --

-- Proportion of patients with adverse events comparable between TEPEZZA and placebo groups and no new safety signals were identified --

-- In April, the U.S. Food and Drug Administration (FDA) approved an update to the TEPEZZA indication language, specifying its use in all patients with TED regardless of TED activity or duration --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced the presentation of new data from the randomized, double-masked, placebo-controlled Phase 4 clinical trial (NCT04583735) evaluating TEPEZZA in patients with long disease duration and low Clinical Activity Score (CAS), a measure of disease activity. The oral presentation at the Endocrine Society Annual Meeting (ENDO 2023) supports the efficacy and safety of TEPEZZA in TED patients regardless of disease activity or duration. TEPEZZA is the first and only medicine approved by the U.S. Food and Drug Administration (FDA) for the treatment of TED – a serious, progressive, debilitating and potentially vision-threatening rare autoimmune disease.¹

“These data are important because they provide evidence in a controlled, clinical setting that TEPEZZA can significantly improve proptosis and visual functioning as measured by the Graves’ Ophthalmopathy Quality of Life Questionnaire in people who have been living with Thyroid Eye Disease for years and may have thought they were not a candidate for the medicine,” said Raymond Douglas, M.D., Ph.D., the principal investigator of the trial and director of the Orbital and Thyroid Eye Disease Program, Cedars-Sinai Medical Center in Los Angeles. “Thyroid Eye Disease is a heterogenous disease, and its impact is not always immediately visible, affecting patients both physically in day-to-day activities, and mentally due to the emotional distress that accompanies the disease. It is not too late to help those patients with longer-term symptoms.”

As previously reported, the Phase 4 clinical trial met its primary efficacy endpoint (reduction in proptosis) and key secondary efficacy endpoint (proptosis responder rate). At Week 24, per the pre-specified primary analysis method (intent-to-treat), patients treated with TEPEZZA achieved a 2.41 mm reduction in proptosis from baseline compared with 0.92 mm for placebo (p=0.0004) and 62% of patients treated with TEPEZZA had a meaningful improvement in proptosis (≥2 mm) compared with placebo (25%) (p=0.0134). In the pre-specified per-protocol analysis, patients treated with TEPEZZA achieved a 2.44 mm reduction in proptosis from baseline compared with 0.69 mm for those receiving placebo (p=0.0006) and 63% of patients treated with TEPEZZA had a meaningful improvement in proptosis (≥2 mm) compared with placebo (7%) (p=0.0008) at Week 24.

The results presented at ENDO also showed that TEPEZZA improved visual functioning as measured by Graves’ Ophthalmopathy Quality of Life Questionnaire (GO-QOL), a tool used to measure health-related quality of life in TED patients, scaled from 0 (worst) to 100 (best). At Week 24, in the pre-specified analysis in the intent-to-treat population, patients who received TEPEZZA experienced a significantly greater average improvement from baseline for visual functioning (8.73) compared with placebo (2.41) (p=0.03). At Week 24, the change from baseline for appearance, also measured by GO-QOL, was 10.03 for TEPEZZA and 7.19 for placebo (p=0.65). The appearance subscale endpoint was not statistically significant: at Week 24, per the pre-specified primary analysis method (intent-to-treat), patients who received TEPEZZA experienced a 10.03 improvement in appearance compared with 7.19 for placebo (p=0.65). No new safety signals were observed.

“Over the past few years, our understanding of Thyroid Eye Disease and the importance of TEPEZZA has continued to expand, fueled by the curiosity and efforts of leaders in the field and our combined commitment to ongoing research,” said Beth Scott, OD, MS, vice president, medical affairs, Horizon. “These trial data support the potential role of TEPEZZA across a broad range of Thyroid Eye Disease patients, no matter how long they have been living with the disease or how much disease activity they have.”

Trial Design

This randomized, double-masked, placebo-controlled, parallel-group, multicenter trial evaluated the efficacy, safety, and tolerability of TEPEZZA (n=42) compared to placebo (n=20) in adults who have lived with TED from two to 10 years duration prior to the study and have low CAS. The primary efficacy objective was to measure the effect of TEPEZZA versus placebo in the change of proptosis measurements in the study eye from baseline at Week 24. All study participants were required to have an initial diagnosis of TED two to 10 years prior to screening, and a CAS of ≤1 in both eyes for at least one year prior to screening or all of the following one year prior to screening: no progression in proptosis, no progression in diplopia and no new inflammatory TED symptoms. Participants could not have had prior orbital irradiation, orbital decompression surgery or strabismus surgery. The mean duration of disease for TEPEZZA and placebo patients was 5.1 years (SD 1.88) and 5.4 years (SD 1.61), respectively. The mean CAS for TEPEZZA and placebo patients was 0.3 (SD 0.47) and 0.5 (SD 0.51), respectively.

About Thyroid Eye Disease (TED)

TED is a serious, progressive 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.^2,3 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.^4,5

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. 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. 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. 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.
5. 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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