Merck’s WELIREG receives positive CHMP opinion for VHL tumours and advanced RCC

Merck, known as MSD outside the U.S. and Canada, has moved a step closer to offering innovative treatment options in Europe. The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive CHMP opinion recommending conditional approval of WELIREG (belzutifan). This hypoxia-inducible factor inhibitor could provide a much-needed systemic therapy option for adult patients with VHL disease-associated tumours and those battling advanced clear cell RCC, who have exhausted existing lines of treatment.

If approved by the European Commission, WELIREG would be the first oral HIF-2α inhibitor available in the EU, reinforcing Merck’s commitment to addressing unmet medical needs in oncology.

Breakthrough for VHL Disease

The CHMP recommendation stems from compelling evidence derived from the Phase 2 LITESPARK-004 trial. WELIREG demonstrated remarkable efficacy in treating various VHL disease-associated tumours, including renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, and pancreatic neuroendocrine tumours (pNET), particularly for patients unsuitable for localised surgical procedures.

In the trial, the drug achieved a 49% objective response rate (ORR) in RCC patients, with durable results persisting for up to 22 months. For CNS hemangioblastomas, WELIREG’s ORR reached 63%, with an impressive 73% of responders maintaining their outcomes for at least a year. The drug also excelled in treating VHL-associated pNET, recording an ORR of 83% and confirming its potential as a systemic therapy option for patients with limited alternatives.

WELIREG could become the first treatment specifically approved for VHL-associated tumours in the EU, setting a precedent for addressing this rare and complex condition.

Advanced Clear Cell RCC: New Hope for Patients

For patients with advanced clear cell RCC, WELIREG offers hope where other therapies have failed. The CHMP recommendation draws on findings from the Phase 3 LITESPARK-005 trial, which highlighted WELIREG’s effectiveness in patients whose disease progressed after two or more prior therapies, including PD-(L)1 inhibitors and VEGF-targeted treatments.

The study showed that WELIREG reduced the risk of disease progression or death by 25% compared to everolimus, a commonly used therapy. Additionally, WELIREG achieved an ORR of 22%, significantly outperforming the 4% response rate seen with everolimus. These results underscore its ability to address the unmet medical needs of this patient population.

Clinical and Global Progress

The CHMP’s recommendation marks a significant milestone in WELIREG’s journey toward regulatory approval in the European Union. The European Commission is expected to make a final decision by the first quarter of 2025. Merck’s drug has already gained approval in the United States for similar indications, including its 2021 authorisation for treating VHL disease-associated tumours and its 2023 approval for treating advanced clear cell RCC.

Dr. Marjorie Green, Senior Vice President of Oncology at Merck Research Laboratories, stated that the company is deeply committed to addressing unmet medical needs through groundbreaking treatments like WELIREG. She highlighted the drug’s potential to transform care for patients with rare and hard-to-treat conditions.

Future Outlook

With the potential approval of WELIREG, Merck is poised to redefine standards in oncology care across the European Union. By offering a targeted systemic therapy option for both VHL disease-associated tumours and advanced clear cell RCC, WELIREG could fill critical treatment gaps and improve outcomes for patients with limited choices.

The combination of strong clinical trial results, novel mechanisms of action, and proven efficacy in heavily pre-treated populations positions WELIREG as a groundbreaking addition to cancer treatment options worldwide.