New Post-Marketing Safety Analysis Shows Rate of Hearing-Related Events Associated with TEPEZZA® (teprotumumab-trbw) Comparable with Clinical Trial Observations

-- TEPEZZA analysis reinforcing sustained efficacy also presented at NANOS 2022 --

Horizon Therapeutics plc (Nasdaq: HZNP) today announced results from a new post-marketing safety analysis of hearing events associated with TEPEZZA for the treatment of Thyroid Eye Disease (TED). These findings, along with data on the sustainability of response to TEPEZZA, were presented at the 48^th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS 2022), Feb. 12-17, in Austin, Texas. 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 and potentially vision-threatening rare autoimmune disease.¹

Since the FDA approval in 2020, Horizon has conducted post-marketing monitoring to understand the overall safety profile of TEPEZZA, including hearing-related events. Among the thousands of patients included in this 19-month analysis (Jan. 2020 - Aug. 2021), approximately 10% of all cases reported to the safety database have included a hearing-related event. The most frequently reported hearing event was hypoacusis (reduction in hearing), followed by tinnitus (ringing in the ears). The mean age of the patient, where known, was 59.3 years. No new safety concerns were observed in the post-marketing database.²

This is comparable with what was seen in the pooled OPTIC Phase 3 and OPTIC-X open-label extension trials for TEPEZZA. Hearing-related adverse events were reported in 9.5% (8/84) of patients treated with TEPEZZA, which were mild or moderate in severity, versus 0% of patients who received placebo. Adverse events experienced in the clinical trials were manageable, with few discontinuations or therapy interruptions.^3,4

“The majority of hearing-related adverse events in the pivotal trials and post-approval have been mild to moderate and reversible, but as with any medicine, it is important to monitor patients,” said Kimberly Cockerham, M.D., adjunct clinical associate professor, Department of Ophthalmology, Stanford University School of Medicine, and a primary author of the report. “Notably, we continue to see high patient adherence to TEPEZZA, with more than 90% of patients completing their full course of treatment in the clinical studies and post-approval. This speaks to the favorable benefit-risk profile of TEPEZZA for people living with Thyroid Eye Disease.”

A separate analysis presented at NANOS 2022 examined the sustainability of response to TEPEZZA over the follow-up periods from the Phase 2 and OPTIC Phase 3 clinical trials and the OPTIC-X open-label extension study. A total of 121 patients were analyzed, with 9 patients receiving additional medications and/or surgery during the follow-up periods. Of those with data available, the majority of patients treated with TEPEZZA were proptosis, diplopia and European Group on Graves’ Orbitopathy (EUGOGO) composite outcome responders up to 51 weeks after their last infusion.⁵

“Managing the disabling symptoms of Thyroid Eye Disease can be difficult for patients, both physically and emotionally, and before TEPEZZA, there was a significant unmet medical need for an effective treatment,” said Jeffrey W. Sherman, M.D., FACP, executive vice president, chief medical officer, Horizon. “Ongoing research reinforces the significant impact TEPEZZA can have on people living with this devastating disease. We are committed to continuing our research to support a positive patient experience with this important medicine.”

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.^6,7 This leads to a cascade of negative effects, which may cause long-term, irreversible damage. TED begins with an acute (active) phase where inflammatory signs and symptoms, such as eye pain, swelling, proptosis (eye bulging) and diplopia (double vision), progress over time.^1,8 The disease then enters a chronic phase where inflammation is no longer present or has markedly diminished, but significant signs and symptoms may remain. As TED progresses, the serious damage it can cause includes proptosis (eye bulging), strabismus (misalignment of the eyes) and diplopia (double vision) – and in some cases can lead to blindness.^8,9

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 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.

References

1. Barrio-Barrio J, et al. Graves' Ophthalmopathy: VISA versus EUGOGO Classification, Assessment, and Management. Journal of Ophthalmopathy. 2015;2015:249125.
2. Cockerham, K, et al. Post-Marketing Surveillance of Hearing-related Adverse Events in Patients With TED Treated With Teprotumumab. Poster session presented at: 48^th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS); 2022 Feb. 12-17; Austin, TX.
3. Smith TJ, et al. Teprotumumab for Thyroid-Associated Ophthalmology. N Engl J Med. 2017;376:1748-1761.
4. Douglas RS, et al. Teprotumumab for the Treatment of Active Thyroid Eye Disease. N Engl J Med. 2020;382:341-352.
5. Subramanian, P, et al. Sustainability of Teprotumumab Efficacy in Thyroid Eye Disease. Paper presented at: 48^th Annual Meeting of the North American Neuro-Ophthalmology Society (NANOS); 2022 Feb. 12-17; Austin, TX.
6. Weightman DR, et al. Autoantibodies to IGF-1 Binding Sites in Thyroid Associated Ophthalmopathy. Autoimmunity. 1993;16(4):251–257.
7. 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.
8. 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.
9. 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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