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Teprotumumab (TEPEZZA®) is a human monoclonal antibody targeting the insulin-like growth factor 1 receptor (IGF-1R), blocking its activation and signalling. Thereby, it prevents symptoms of moderate-to-severe thyroid eye disease (TED, Graves´ orbitopathy), including lid retraction, soft tissue involvement, proptosis and diplopia. Currently, teprotumumab is under evaluation by the European Medicines Agency (EMA) for market authorisation and is expected to be approved by the European Commission (EC) in July 2025. Compared to placebo, teprotumumab significantly improved proptosis response, clinical activity score (CAS), and Graves’ ophthalmopathy-specific quality-of-life scores in three clinical studies and one observational study. The most frequent adverse events included muscle spasms, alopecia, nausea and fatigue. Additionally, 12-15% of teprotumumab patients reported (partially irreparable) hearing damage. TED reactivation rates varied from 26% to 29%, and 65.4% of patients experienced a regression. Notably, 33% of patients maintained a sustained response through the 24-month follow-up. The available evidence is limited, as efficacy has only been tested against a placebo, not the standard of care.

Fidanacogene elaparvovec (BEQVEZ®) received conditional marketing authorisation from the European Commission on 24th July 2024 for treating severe and moderate haemophilia B. It is the second gene therapy approved in Europe for this condition and is classified as an Advanced Therapy Medicinal Product (ATMP). This gene therapy is approved for adults with no history of factor IX inhibitors and no detectable antibodies against AAVRh74var. It is administered as a one-time intravenous infusion and uses a viral vector to introduce the functioning coagulation factor IX gene into liver cells, where it continuously produces the missing factor.

Fidanacogene elaparvovec demonstrated a 71% reduction in annual bleeding rate compared to previous FIX prophylaxis in a single-arm Phase 3 study (BENEGENE-2, n=45). The effect was maintained for up to 48 months. Adverse effects occurred in 84% of patients treated, with 16% experiencing serious reactions. The most common side effect was elevated aminotransferase levels (53%). The study's methodological limitations include a short follow-up period, a lack of a control group, and changes to the primary endpoint. As the therapy is administered only once intravenously, interviewed patients express optimism about the reduced treatment burden and improved quality of life that may result from a simplified form of therapy and freedom from treatment. At the same time, patients are concerned about the uncertainty regarding long-term efficacy and potential side effects. Therefore, it is recommended that patients receive an infusion in specialised centres with subsequent monitoring in local facilities. Additionally, mandatory follow-up of all treated patients is deemed necessary.

In Austria, 130 patients were reported by the Austrian Haemophilia Society (ÖHR) in 2024. Of these, 22.3% were affected by moderate haemophilia and 24.6% by severe haemophilia. Currently, no price for fidanacogene elaparvovec is available in Europe, so the budget impact analysis (BIA) was based on a preliminary price of 3.4 million euros per administration. Assuming nine patients receive the therapy with an increasing uptake over three years (year 1: 20%, year 2: 30%, year 3: 50%), the total three-year budget impact would amount to approximately 41 million euros. This represents a 3-fold increase compared to the current treatment. In the long term (after about 12 years), costs could be offset by the elimination of prophylaxis.

Exagamglogene autotemcel (exa-cel, Casgevy^®) received conditional marketing authorization from the European Medicines Agency (EMA) on February 9, 2024, as the first CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based gene therapy. It is classified as an Advanced Therapy Medicinal Product (ATMP) and has orphan drug status for two indications. Exa-cel is approved for treating transfusion-dependent ß-thalassemia (TDT) and severe sickle cell disease (SCD) in patients aged twelve years or older who are eligible for hematopoietic stem cell transplantation but lack a human leukocyte antigen (HLA)-matched related donor.

The studies to date (two single-arm studies) show a significant improvement in symptoms in the majority of patients treated. In beta-thalassemia, 32 out of 35 people no longer needed blood transfusions after the therapy. In sickle cell disease, 29 out of 30 patients no longer had severe pain crises. These improvements lasted for at least one to two years in both diseases. The patients' quality of life was noticeably improved as a result. Long-term experience is not yet available.