WELIREG (belzutifan) - Von Hippel-Lindau disease (VHL)

The clinical benefit of WELIREG (belzutifan) 40 mg film-coated tablets is moderate in the MA indication. The Committee makes maintenance of the moderate clinical benefit conditional on its reassessment within a maximum period of 5 years; the Committee would like to have access to comparative data versus the usual treatment without WELIREG, at least versus an external comparator (e.g. natural course of the disease) from a historic registry.

Considering:

• observation of a global response rate of:
  • 2% (n = 41/61; CI95% [54.0; 78.7]) in the overall LITESPARK-004 study population and 83.3% (n = 15/18; CI95% [58.6; 96.4]) in the cohort B1 population of the LITESPARK-015 study, i.e. in patients with measurable solid RCC tumours associated with VHL disease,
  • 0% (CI95% [33.7; 62.6]) and 90.9% (CI95% [70.8; 98.9]) respectively in the VHL- CNS (n = 50) and VHL- pNET (n = 22) groups in the LITESPARK-004 study,
  • 0% (CI95% [26.2; 87.8]) and 66.7% (CI95% [34.9; 90.1]) respectively in the VHL- CNS (n = 10) and VHL- pNET (n = 12) groups in the LITESPARK-015 study.

This in a disease context involving tumours that do not tend to regress spontaneously and that have a highly variable course (expert opinion).

• the unmet medical need to have access to effective, well-tolerated medicinal products in patients for whom localised procedures are unsuitable;

and taking into account:

• the absence of comparative data due to the design of the LITESPARK-004 and LITESPARK-015 studies;
• the absence of data from a single-arm clinical trial with external control arm, for example, or from other forms of indirect comparison of good methodological quality in order to assess the added value of the medicinal product;
• the absence of robust data on morbidity and mortality endpoints;
• uncertainties with respect to the safety profile of belzutifan due to a new mechanism of action and limited experience;
• the lack of quality of life data.

the Committee deems that WELIREG (belzutifan) 40 mg film-coated tablets provides a minor clinical added value (CAV IV) in the current care pathway and for patients for whom localised procedures are unsuitable.