One of the major breakthroughs this year the hypoxia-inducible factor (HIF)-2α inhibitor: MK6482 for von Hippel-Lindau (VHL) disease–related clear cell renal cell carcinoma (RCC). VHL disease is a hereditary disease that affects many organs of the body, such as the eyes, brain, spine, pancreas, kidneys and lymphatic system. It is caused by a mutation in the VHL gene, which produces HIF2α, and this can cause the growth of tumours. Currently, there are no drugs to treat VHL disease and patients are followed-up and treated by the removal of tumours and management of the disease to prevent organ damage or the development of metastatic disease.
MK6482 is an inhibitor of HIF2α and has shown promising results in a phase II study in patients with VHL RCC. There were 61 patients in the study, and the response rate was 36% with an additional 11.5% unconfirmed responses. MK6482 was very well tolerated, with anaemia being the most common side effect which was successfully treated. Only 1 patient come off study for treatment-related mild dizziness.
On the basis of these data, MK6482 was granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA), and will be submitted to the FDA for approval shortly. If approved, this will be the first drug available for people with VHL disease and will revolutionise care for this patient population.