MSD claims 2nd FDA approval for Welireg, in kidney cancer


The FDA has approved MSD’s oral HIF-2 alpha inhibitor Welireg for a second cancer indication, relapsed or refractory advanced renal cell carcinoma (RCC), the most common form of kidney cancer.

The green light comes two years after Welireg (belzutifan) became the first drug in the class to be approved for marketing, initially for von Hippel-Lindau (VHL) disease, an inherited condition that can cause tumours to develop in various organs of the body.

MSD – known as Merck & Co in North America - acquired Welireg as part of its $2.2 billion takeover of Peloton Therapeutics in 2019, which included an upfront payment of $1.05 billion.

The approval in RCC is for patients previously treated with PD-1/L1 and VEGF-targeted therapies, and according to Marjorie Green, head of late-stage oncology at Merck Research Laboratories (MRL) in the US, is “the first new therapeutic class available for eligible patients with advanced RCC in nearly a decade.”

RCC also unlocks a much larger patient population for the drug and is a key part of MSD’s blockbuster sales aspirations for Welireg, along with a move into glioblastoma multiforme, a hard-to-treat form of brain cancer. Sales of the drug were $146 million in the first nine months of the year, up 75% on the same period of 2022.

The RCC approval comes after a priority review by the FDA and is based on the results of the phase 3 LITESPARK-005 trial, in which the drug showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to everolimus, a go-to therapy for the disease.

After 18 months of follow-up, 22.5% of patients remained free of progression with Welireg, compared to 9% with everolimus, according to results presented at this year’s ESMO cancer congress in October. There was also a trend towards improved overall survival, with 55.2% and 50.6% of patients, respectively, still alive at that time point.

Renal cell carcinoma is by far the most common type of kidney cancer, accounting for about 9 out of 10 kidney cancer diagnoses, with approximately 15% of patients diagnosed at an advanced stage. The cancer is about twice as common in men than in women, and most cases are discovered incidentally during imaging tests for other abdominal diseases.

LITESPARK-005 is one of four pivotal trials testing Welireg’s potential in RCC. The others are LITESPARK-011 and LITESPARK-012, evaluating Welireg in the second-line and treatment-naïve advanced disease settings, respectively, and LITESPARK-022, which is testing the drug in the adjuvant setting for locally advanced RCC.