Blueprint's mastocytosis drug Ayvakit cleared for NHS use

NICE has recommended broad use of Blueprint Medicines' recently-approved therapy for rare blood disorder advanced systemic mastocytosis (ASM) by the NHS in England and Wales, including first-line therapy.

About 1 in 10,000 people in the UK are thought to be living with systemic mastocytosis, of whom around 10% have an advanced form of the disease.

The disorder results in the accumulation of inflammatory mast cells in the body, causing symptoms like itching, fever, abdominal pain and nausea. Severe cases can lead to organ damage, bone fracture, and anaemia, and people with ASM typically have a life expectancy ranging from six months to around three-and-a-half years.

Ayvakit has been recommended by NICE for ASM – an umbrella term that covers aggressive systemic mastocytosis, systemic mastocytosis with an associated haematological neoplasm (SM-AHN), and mast cell leukaemia (MCL).

The move makes Ayvakit an alternative to current therapies, including Novartis' Rydapt (midostaurin) – which was backed by NICE for ASM in 2021 and has been the preferred first-line option to date – and off-label use of chemotherapy agent cladribine, which is generally used second-line.

Blueprint's drug inhibits a range of tyrosine kinase enzymes, including D816V mutant KIT, the most common mutation in SM, occuring in about 90% of cases.

"Traditionally, patients with ASM, SM-AHN, and MCL have faced a poor prognosis, with limited treatment options to address the life-threatening organ damage associated with the disease," said Deepti Radia, a consultant haematologist at Guy's and St Thomas' NHS Foundation Trust and an investigator on the PATHFINDER and EXPLORER trials that support Ayvakit's approval.

"In clinical studies, the majority of evaluable patients responded to treatment with avapritinib, with a subset achieving complete remissions with full or partial haematologic recovery," she added.

Ayvakit is also approved as a treatment for gastrointestinal tumours (GIST) in the UK, but was never launched for that indication. The drug is also reimbursed in EU countries, including the EU4 markets of Germany, Italy, Spain, and France.

Worldwide sales of the drug have taken off following its approval for ASM, reaching $128 million in the third quarter of this year – all but $125 million from the US – and are predicted by the company to top $475 million for 2024 as a whole.

Analysts have suggested that, in time, Ayvakit could displace Rydapt as the go-to therapy for ASM, driving sales of the drug – which has a pretax list price of £26,667 for a 30-day supply in the UK – above the $1 billion threshold. NICE's recommendation is predicated on a confidential discount for the NHS.