EMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Welireg (belzutifan) in adults with certain von Hippel-Lindau (VHL) disease-associated tumours and in adults with previously treated advanced kidney cancer (RCC).
VHL disease is a life-threatening rare genetic condition where people are more likely to develop non-cancerous or cancerous tumours, often in their eyes, brain, spine, kidneys, and pancreas. These growths may cause long-term debilitating symptoms like vision problems, headaches, or high blood pressure depending on their size and location. This disease, which affects approximately 3 in 100,000 people in the EU, is caused by a defect in a single gene, called the VHL gene, which is responsible for the production of a protein that prevents tumour formation.
In the EU, there are no systemic therapeutic options for treating VHL disease-associated tumours for which localised procedures (such as surgery, radiation, or ablation) are unsuitable or undesirable. While these procedures temporarily address individual tumours, they are not curative and new tumours continue to occur. Therefore, there is an unmet need for treatment options that would reduce the size and/or the growth rate of VHL tumours.
Welireg (belzutifan) is administered orally once daily. It blocks the activity of hypoxia-inducible factor 2 alpha (HIF-2α), which regulates cellular proliferation, blood vessel formation and tumour growth. By inhibiting HIF-2α, the medicine counters the effects of defective VHL protein, shrinking the VHL disease-associated tumours. Welireg also targets advanced clear cell renal cell carcinoma (RCC), a type of cancer in which defective VHL protein is present in most cases.
The recommendation is based on the results of two main clinical studies. One trial is an ongoing phase 2, single-arm, open-label study to evaluate the efficacy and safety of belzutifan in 61 patients with at least one VHL-RCC. Belzutifan demonstrated that a clinically relevant percentage of patients (63.9%) have a partial or complete durable response to the treatment.
The other trial is an open-label, randomised phase 3 study comparing belzutifan to everolimus in 746 patients with unresectable, locally advanced or metastatic RCC that has progressed after prior targeted therapies. Results demonstrated a statistically significant improvement in progression-free survival for patients treated with belzutifan compared to everolimus. The approved indication concerns a subgroup of patients from this trial.
The most common side effects associated with this medicine are low red blood cell counts (anaemia), fatigue, nausea, shortness of breath, dizziness and low oxygen levels (hypoxia). Anaemia and hypoxia can be severe and lead to dose interruption, dose reduction or discontinuation of the treatment.
Welireg is recommended for a conditional marketing authorisation, one of the EU’s regulatory mechanisms to facilitate early access to medicines that fulfil an unmet medical need. This type of approval allows the Agency to recommend a medicine for marketing authorisation with less complete data than normally expected, if the benefit of a medicine’s immediate availability to patients outweighs the risk inherent in the fact that not all the data are yet available.
In order to confirm the efficacy and safety of Welireg, especially in patients with VHL-associated tumours, the marketing authorisation holder will have to submit the final results from the currently ongoing phase II trial by Q1 2027, as well as data from at least 64 patients from a supportive study.
The opinion adopted by the CHMP is an intermediary step on Welireg’spath to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
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