NICE Recommends Blueprint Medicines' Ayvakyt for Advanced Systemic Mastocytosis on NHS
Key Insights
NICE has recommended Ayvakyt (avapritinib) for NHS use in England and Wales for advanced systemic mastocytosis (search), including first-line treatment.
The recommendation covers aggressive SM, SM with associated haematological neoplasm, and mast cell leukaemia, offering an alternative to current therapies like midostaurin.
Clinical trials showed the majority of evaluable patients responded to avapritinib, with some achieving complete remissions with haematologic recovery.
The National Institute for Health and Care Excellence (NICE) has recommended broad NHS use of Blueprint Medicines' Ayvakyt (avapritinib) for adults with advanced systemic mastocytosis (search) (ASM) in England and Wales, positioning the targeted therapy as a new first-line option for this rare and life-threatening blood disorder.
The recommendation encompasses the full spectrum of advanced disease, including aggressive systemic mastocytosis, systemic mastocytosis with an associated haematological neoplasm (SM-AHN), and mast cell leukaemia (MCL).
Addressing a Critical Unmet Need
Systemic mastocytosis affects approximately 1 in 10,000 people in the UK, with around 10% of those individuals having an advanced form of the disease. The disorder is characterised by the accumulation of inflammatory mast cells throughout the body, producing symptoms such as itching, fever, abdominal pain, and nausea. In severe cases, patients may experience organ damage, bone fractures, and anaemia. People with ASM typically face a life expectancy ranging from six months to approximately three-and-a-half years.
"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 supporting Ayvakyt's approval.
Mechanism and Clinical Evidence
Ayvakyt inhibits a range of tyrosine kinase enzymes, including D816V mutant KIT (search), which is the most common mutation in systemic mastocytosis, occurring in approximately 90% of cases. The clinical evidence underpinning the NICE recommendation draws from the PATHFINDER and EXPLORER trials.
"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," Radia added.
Shifting the Treatment Landscape
The NICE decision makes Ayvakyt an alternative to current therapies, including Novartis' Rydapt (midostaurin) — which received NICE backing for ASM in 2021 and has been the preferred first-line option — and off-label use of the chemotherapy agent cladribine, typically reserved for second-line treatment.
NICE's recommendation is predicated on a confidential discount for the NHS. Ayvakyt carries a pre-tax list price of £26,667 for a 30-day supply in the UK.
Commercial Trajectory
Worldwide sales of Ayvakyt have accelerated following its approval for ASM, reaching $128 million in the third quarter of this year, with all but $125 million originating from the US market. Blueprint Medicines projects full-year 2024 sales to exceed $475 million. Analysts have suggested that Ayvakyt could eventually displace Rydapt as the standard therapy for ASM, potentially driving sales above the $1 billion threshold.
Ayvakyt is also approved as a treatment for gastrointestinal stromal tumours (GIST) in the UK, though it was never launched for that indication. The drug is reimbursed in EU countries, including the EU4 markets of Germany, Italy, Spain, and France.