Merck & Co – known as MSD outside of the US and Canada – has announced that its Welireg (belzutifan) has been approved by the US Food and Drug Administration (FDA) as the first oral therapy for pheochromocytoma or paraganglioma (PPGL), two rare tumour types.
The drug has been specifically authorised to treat adult and paediatric patients aged 12 years and older with locally advanced, unresectable or metastatic PPGL.
Up to 2,000 new cases of PPGL, sometimes referred to as pheo par, are diagnosed in the US every year. Pheochromocytoma forms in the adrenal gland, while paraganglioma forms outside it, and both can be caused by genetic syndromes or mutations.
Merck gained access to Welireg in 2019 through its $1.1bn buyout of Peloton Therapeutics. The drug is designed to inhibit the transcription factor hypoxia-inducible factor 2 alpha (HIF-2α), which regulates cellular proliferation, angiogenesis and tumour growth, and is already approved in the US for certain patients with von Hippel-Lindau (VHL) disease and renal cell carcinoma (RCC).
The FDA’s latest decision was supported by results from the phase 2 LITESPARK-015 trial, which enrolled 72 patients in a single cohort who had measurable disease, a documented histopathological PPGL diagnosis, and locally advanced or metastatic disease that was not amenable to surgery or curative treatment.
The objective response rate in Welireg-treated patients was 26% and median duration of response was 20.4 months. Additionally, among patients on baseline antihypertensive medications, 32% experienced a reduction in at least one antihypertensive medication by 50% or more for a minimum of six months.
Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said: “For patients with advanced PPGL, there has been a lack of approved systemic treatment options available to help manage their disease, underscoring the importance of this approval in the US.”
The decision comes just three months after the European Commission granted conditional approval to Welireg for VHL disease and RCC.
“The approval of Welireg in the EU introduces the first and only systemic treatment option for adult patients with certain VHL disease-associated tumours for whom localised procedures are unsuitable, and offers a new option for adult patients with advanced clear cell RCC that progressed following a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies,” Green noted at the time.
