Teprotumumab (Tepezza®): A New Medication for Eye Disease in Graves’ Disease

Teprotumumab (Tepezza®) was recommended for approval by the European Medicines Agency (EMA) in April 2025. It was already approved for treatment by the U.S. Food and Drug Administration (FDA) in January 2020.

Teprotumumab is a drug treatment for endocrine orbitopathy (EO), also known as Thyroid Eye Disease (TED).

What happens in this autoimmune disease (EO)?

In EO, the body produces autoantibodies that attack the TSH receptors, which are normally activated by thyroid-stimulating hormone (TSH). These receptors are found not only in the thyroid gland, but also in the tissues behind the eye, which is why EO often occurs alongside Graves’ disease.

In EO, inflammation develops in the eye socket (orbit), leading to swelling of the eye muscles and connective tissue. This causes:

• Pressure and pain behind the eye
• Redness and puffiness of the eyelids and tissue
• Swelling causes the eyeball to protrude forward (exophthalmos)

In severe cases:

• The eyelids can no longer close properly
• Eye movement is limited due to muscle involvement
• Patients may develop a fixed stare and double vision (diplopia)
• If the optic nerve is compressed or the cornea becomes damaged (due to the inability to close the eye), vision loss or blindness may occur

Standard treatment includes:

• Antithyroid medications to normalize thyroid hormone levels
• Corticosteroids to reduce inflammation
• Retrobulbar radiation therapy
• In severe cases, a decompression surgery may be needed to relieve pressure and prevent blindness

How does Teprotumumab work?

Teprotumumab is a human monoclonal antibody that targets the IGF-1 receptor (IGF-1R) – the receptor for insulin-like growth factor-1.

It is used to treat active, moderate to severe endocrine orbitopathy (also called thyroid eye disease or Graves’ orbitopathy) in adults.

Where are IGF-1 receptors found?

 Why are IGF-1 receptors important in the eye (orbit)?

1. Orbital fibroblasts:

• Special fibroblast cells in the eye socket express a high number of IGF-1 receptors.
• In autoimmune diseases like Graves’ disease, these cells can be abnormally activated.

1. Abnormal activation in EO:

• In EO, patients form autoantibodies against the TSH receptor (TSHR).
• These antibodies bind not only to TSHR, but also to a complex formed between TSHR and IGF-1R.
• This leads to overactivation of IGF-1 signaling in the eye tissue → causing tissue growth, inflammation, and swelling.

1. Resulting symptoms include:

• Fat and muscle buildup behind the eye
• Swelling and fibrosis of eye muscles
• Symptoms such as exophthalmos, double vision, pain, and pressure sensation

Does IGF-1/IGF-1R also play a role in thyroid disease?

Yes. IGF-1 and its receptor are also involved in thyroid disorders, especially Graves’ disease, though they are not the main cause.

Graves’ disease (autoimmune hyperthyroidism):

• Caused by autoantibodies (TRAb) that activate the TSH receptor on thyroid cells.
• This leads to overproduction of thyroid hormones (T3, T4) → hyperthyroidism. Role of IGF-1R:

• Research shows that TSHR and IGF-1R form a functional complex on thyroid and fibroblast cells.
• TRAb antibodies can activate this receptor complex, not just TSHR alone.
• IGF-1R activation results in:
  • Cell growth and proliferation
  • Increased hormone production
  • Boosted immune cell activity Relevance to disease progression:

• IGF-1R amplifies the autoimmune reaction.
• It plays a central role in EO, but only a modulating role in the thyroid.

Dosage:

Dosage of Teprotumumab (Tepezza®) is weight-based:

1. Initial dose:
   • 10 mg per kilogram (kg) of body weight
2. Subsequent doses:
   • 20 mg/kg body weight
   • Administered every three weeks
3. Total duration of therapy:
   • 8 infusions over approximately 21 weeks (about 5 months)

Example of a treatment schedule:

Important Notes:

• Each infusion should be administered over at least 60 minutes.
• Patients must be monitored during and after the infusion for possible side effects.
• Teprotumumab is contraindicated during pregnancy and may harm the unborn child – pregnancy must be excluded before starting treatment.

Treatment Costs:

The cost of treatment with Teprotumumab (brand name: Tepezza) can be very high.

• In the United States, the price for one 500 mg vial is approximately $18,700.
• Since the dosage is weight-based (initial 10 mg/kg, then 20 mg/kg every 3 weeks for a total of 8 infusions), the total cost for a full treatment cycle for an average adult (80 kg body weight) can exceed €400,000 (USD equivalent).

Availability in Germany:

• Tepezza is not yet approved in Germany. Its launch is expected in 2025.
• Therefore, official pricing for the German market is not yet available.
• It is likely, however, that treatment costs will be comparable to those in the US.

Reimbursement by Health Insurance:

• Because Tepezza is not yet approved in Germany, public health insurance does not currently cover the treatment.
• After approval, reimbursement is expected to be reviewed on a case-by-case basis, especially due to the high costs.
• Patients are advised to contact their health insurance providers early to discuss potential coverage options.

Additional Support:

In the United States, the manufacturer Amgen offers a patient support program called “Amgen By Your Side”.
This program helps patients navigate the insurance process and financial assistance options.

Whether a similar support program will be offered in Germany remains to be seen.

Common Side Effects (≥10% of patients):

 Less common, but potentially serious side effects:

Special Warnings:

• Not for use during pregnancy – effective contraception is required during treatment and for at least 6 months after the last dose.
• In diabetics, regular blood glucose monitoring is important.
• Hearing tests may be needed, as some patients experienced temporary or rarely permanent hearing loss.