Teprotumumab

Teprotumumab (Tepezza) is a treatment for thyroid eye disease (TED), to reduce the symptoms of eye bulging, double vision, eye pain, redness, and swelling. Teprotumumab treats the cause of thyroid eye disease, not just the symptoms, and can be used if you have had thyroid eye disease for months or even years. Teprotumumab brand name is Tepezza by Horizon Therapeutics.

Teprotumumab works by blocking a protein called IGF-1R (insulin-like growth factor-1 receptor), which reduces inflammation and prevents tissue expansion to improve TED symptoms. Improvement in eye bulging started as early as 6 weeks and continued to improve over 24 weeks in the OPTIC trial for teprotumumab-trbw, which was reported in the NEJM

Teprotumumab-trbw is given as an infusion into a vein, usually every 3 weeks, for a total of 8 doses; each infusion takes 60 to 90 minutes to complete.

Teprotumumab FDA approval is for the indication of thyroid eye disease, regardless of TED activity or duration. FDA approval was granted to Horizon Therapeutics on January 21, 2020, after positive results from the Phase 3 confirmatory clinical study OPTIC.

Thyroid eye disease (TED) is an autoimmune disorder in which the immune system attacks tissues around the eyes, resulting in symptoms such as dry or watery eyes, eye redness, bulging eyes, vision problems, and difficulty closing the eyes.

A protein called insulin-like growth factor-1 receptor (IGF-1R) plays a central role in causing the symptoms of TED. In patients with thyroid eye disease, there are elevated levels of IGF-1 receptors in the tissues around the eyes. Activation of these receptors by the immune system leads to inflammation and swelling of the surrounding tissues.

TED is sometimes called Graves' Eye Disease, as it often occurs in people living with Graves’ disease or hyperthyroidism.

Teprotumumab mechanism of action is by targeting and blocking IGF-1R activation and signaling, which helps reduce inflammation and prevent tissue expansion behind the eyes. This, in turn, helps relieve symptoms such as double vision (diplopia), eye bulging (proptosis), redness, dryness, or excessive tearing, and overall eye discomfort.

Tepezza is an insulin-like growth factor-1 receptor inhibitor.

Benefits of teprotumumab in the OPTIC study NCT03298867 were:

• 83% of teprotumumab patients had a significant improvement in eye bulging (proptosis) compared to 10% for patients using placebo treatment at week 24.
• 68% of teprotumumab patients had improved double vision (diplopia) baseline scores by at least one grade, compared to 29% of patients receiving a placebo treatment in Week 24.
• Improvement in eye-bulging started as early as 6 weeks and continued to improve over 24 weeks in clinical trials

Teprotumumab is given as an infusion into a vein, which can take 60 to 90 minutes to complete. It is usually given once every 3 weeks for a total of 8 doses.

A healthcare provider will give you this injection.

Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Infusion reactions can occur with this medicine. Infusion reactions may occur at any time. Infusion reactions that have been reported are usually mild or moderate in severity and can usually be successfully managed with corticosteroids and antihistamines.

Inflammatory bowel disease (IBD) may occur or be exacerbated with this medicine. Patients should be monitored for signs and symptoms of IBD, including patients without a history of IBD. If a flare-up or new IBD is suspected, consider stopping this medicine.

High blood sugar levels (hyperglycemia). This medicine may cause an increase in blood glucose levels. Monitor blood glucose levels and symptoms of hyperglycemia before infusion and while on treatment. Patients who have hyperglycemia or pre-existing diabetes should be under appropriate glycemic control before and while receiving this infusion.

Teprotumumab hearing loss or hearing impairment may be a side effect. This medicine may cause severe hearing impairment including hearing loss, which, in some cases, may be permanent. Patients’ hearing should be assessed before, during, and after treatment with this infusion. Weigh up the benefit-risk ratio of treatment before treatment.

Encephalopathy (brain disease). Cases of encephalopathy have been reported in patients treated with this medicine. Seek immediate medical attention if you experience signs or symptoms of a brain condition, such as confusion, memory problems, or changes in behavior.

To make sure teprotumumab is safe for you, tell your doctor if you have:

• inflammatory bowel disease;
• diabetes or hyperglycemia (high blood sugar);

Pregnancy

This medicine may harm an unborn baby. Use effective birth control to prevent pregnancy while you are receiving the infusion and for at least 6 months after your last dose. Tell your doctor if you become pregnant.

Breastfeeding

It may not be safe to breastfeed while using this medicine. Ask your doctor about any risk.

Common teprotumumab side effects

Common teprotumumab side effects may include:

• Muscle spasms (25%)
• Nausea (17%)
• Diarrhea (12%)
• Headache (8%)
• Tiredness (12%)
• High blood sugar (hyperglycaemia)(10%)
• Hair loss, alopecia (13%)
• Hearing problems (10%)
• Dry skin (8%)
• An altered sense of taste (dysgeusia) (8%)
• Weight decrease (6%)
• Nail disorders (5%)
• Menstrual problems, such as missed periods or irregular bleeding.

These common side effects occurred in 5% or more of patients in two randomized, double-masked, placebo-controlled clinical studies: Study 1 (NCT:01868997) and Study 2 (NCT:03298867).

For more information on the side effects of hearing loss, see “Does Tepezza cause hearing loss?” and the warning section below.

Serious teprotumumab side effects

Get emergency medical help if you have signs of an allergic reaction to this medicine, such as hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

Some serious side effects may occur during an injection or at any time afterward. Tell your caregiver right away if you feel hot, anxious, or short of breath, or if you have a headache, muscle pain, or fast heartbeats.

Call your doctor at once if you have:

• diarrhea (with or without blood);
• stomach cramps;
• bowel movements that occur suddenly;
• loss of bowel control;
• a feeling of not completely emptying your bowels;
• rectal bleeding; or

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• high blood sugar or severe diabetic complications (such as diabetic ketoacidosis) - increased thirst, increased urination, dry mouth, fruity breath odor; or
• severe bowel problems, including a hole in the bowel wall (bowel perforation).
• signs of a brain condition (encephalopathy), such as confusion, memory problems, or changes in behavior.

Teprotumumab infusion may cause side effects of infusion reactions, worsening of inflammatory bowel disease, high blood sugar, and hearing loss or impairment. See Warning Section for more details of these side effects.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Usual Adult teprotumumab Dose for Thyroid Eye Disease

Initial dose: 10 mg/kg intravenous infusionMaintenance dose: 20 mg/kg intravenous infusion every 3 weeks for 7 additional infusions.

Teprotumumab (Tepezza) is available as a 500 mg lyophilized powder in a single-dose vial for reconstitution.

Tepezza (teprotumumab) J code is J3241 (10 mg, injection)J codes are used for medicines that are not taken orally and include injections, inhalations chemotherapies. J codes are important, accurate, and consistent coding for billing and reimbursement purposes.

Your physician will need a J-code when filling out forms for your treatment.

Call your doctor for instructions if you miss an appointment for your infusion.

Since this infusion is given by a healthcare professional in a medical setting, an overdose is unlikely to occur.

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may affect teprotumumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

Click on the Interactions link below for more interactions information.

Review the Teprotumumab Package Insert (Tepezza Package Insert) for more detailed information about this medicine. Discuss any medical questions you have with your doctor or other health care provider. This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

Single dose vialRefrigerate at 2°C to 8°C (36°F to 46°F) in original carton until time of use to protect from light. Do not freeze.

Reconstituted Tepezza solution in the vial and the diluted solution in the infusion bag containing 0.9% Sodium Chloride Injection.

The combined storage time of reconstituted Tepezza solution in the vial and the diluted solution in the infusion bag containing 0.9% Sodium Chloride Injection, USP is a total of 4 hours at room temperature 20°C to 25°C (68°F to 77°F) or up to 48 hours under refrigerated conditions 2°C to 8°C (36°F to 46°F) protected from light. If refrigerated prior to administration, allow the diluted solution to reach room temperature prior to infusion.

Tepezza (teprotumumab) manufactured by Horizon Therapeutics Ireland DAC Dublin, Ireland U.S. License No. 2022.

Distributed by: Horizon Therapeutics USA, Inc. Deerfield, IL 60015