EMA Backs Tepezza for Severe Thyroid Eye Disease

The European Medicines Agency (EMA) has announced that the Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of teprotumumab (Tepezza, Amgen) for the treatment of moderate to severe thyroid eye disease (TED), also known as Graves' orbitopathy, in adult patients.

The recommendation, made during the CHMP’s April 2025 meeting, supports Amgen’s marketing authorization application (MAA) for teprotumumab. According to the EMA summary, the therapy will be made available as a 500 mg powder concentrate for solution for infusion. Notably, teprotumumab is the first treatment to be recommended for severe TED in Europe.

Mechanism of Action: Targeting IGF-1 Receptors to Halt TED Progression

Teprotumumab is a monoclonal antibody that targets and binds to the insulin-like growth factor 1 receptor (IGF-1R). By inhibiting IGF-1R activity, it blocks autoimmune activation of orbital fibroblasts, a key mechanism driving the inflammation and tissue expansion associated with TED.

Clinical Trial Results Demonstrate Efficacy in Active and Chronic TED

The CHMP’s opinion was based on results from three randomized, placebo-controlled phase 3 trials involving 225 patients with active TED, as well as a separate phase 3 trial including 62 patients with chronic TED.

According to the EMA, outcomes showed that:

• After 24 weeks, patients treated with teprotumumab experienced a significant reduction in proptosis (–2.0 mm to –2.3 mm)

• Clinical Activity Score (CAS) was significantly reduced, indicating decreased inflammation

• In patients with chronic TED, the reduction in proptosis was smaller (–1.5 mm) but still meaningful

Safety Profile and Risk Management

The most commonly reported adverse events associated with teprotumumab included:

• Muscle spasms

• Hyperglycemia

• Fatigue

• Nausea

• Headache

• Diarrhea

• Alopecia

The EMA also highlighted important safety concerns:

• Evidence of severe and potentially permanent hearing impairment

• Potential risks to fetal development, based on pre-clinical findings

The agency stated that additional risk management measures will be required to mitigate these potential risks in clinical use.

Next Steps: European Commission Decision Expected by July 2025

The European Commission will now review the CHMP’s opinion and make a final determination on whether to grant EU-wide marketing authorization for teprotumumab. According to the EMA, a decision is typically issued within 67 days of the CHMP recommendation. Under this timeline, a final decision is anticipated by 1 July 2025.