NICE Recommends Novartis’ Rydapt (Midostaurin) for Advanced Systemic Mastocytosis Treatment

Compiled and translated by | Fan Dongdong

Recently, the UK's National Institute for Health and Care Excellence (NICE) has decided to recommend Novartis' Rydapt (midostaurin) for the treatment of aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, or mast cell leukemia (collectively referred to as AdvSM).

Following NICE recommendation, Rydapt has become the first and only licensed treatment for AdvSM in the UK, having previously been demonstrated to provide therapeutic benefits for adults with the disease. Previously, clinical treatment options for UK patients were limited to symptom management, whereas the newly approved Rydapt is a targeted therapy that inhibits KIT signaling, cell proliferation, and histamine release, and induces mast cell apoptosis.

According to trial results published in *The New England Journal of Medicine* this January, Rydapt inhibits the KIT D816V mutation that drives disease progression in mastocytosis. Trial data demonstrated an overall response rate of 60% in the Rydapt group, with 45% of patients achieving complete resolution of at least one mast cell-mediated organ impairment. The median overall survival for patients in the Rydapt group was 28.7 months, and the median progression-free survival was 14.1 months. In terms of safety, 56% of patients in the Rydapt group required dose reductions due to drug toxicity; however, 32% of these patients were able to re-escalate their doses to the baseline levels used at trial initiation. The most common adverse events associated with Rydapt were low-grade nausea, vomiting, and diarrhea.

This medication is an oral multi-kinase inhibitor capsule containing a 25 mg dose of midostaurin. Upon administration, the drug inhibits multiple key kinases that regulate cell growth, including FLT3, thereby interfering with the growth and proliferation of cancer cells in the patient.

In April 2017, the U.S. Food and Drug Administration (FDA) approved Rydapt in combination with chemotherapy for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) harboring a specific FLT3 gene mutation, making Rydapt the first targeted therapy in the United States to be used in combination with chemotherapy for AML at the time. Compared with other AML patients, those with FLT3 mutations face a higher risk of relapse and lower survival rates. Against a backdrop of historically limited treatment options, Rydapt, developed by Novartis, has transformed this clinical landscape.

Additionally, the FDA has approved the drug for the treatment of aggressive systemic mastocytosis, a rare blood disorder. Previously, the FDA had granted Priority Review designation for the Rydapt marketing application, Fast Track designation (for mastocytosis), and Breakthrough Therapy designation (for acute myeloid leukemia).

Regarding competitors, Ayvakit (avapritinib), developed by Blueprint, received FDA approval in June this year for the treatment of adult patients with advanced systemic mastocytosis (SM), including aggressive SM, SM with an associated hematological neoplasm, and mast cell leukemia. Clinical trial results demonstrated that Ayvakit treatment elicited durable clinical responses, including complete responses, in both treatment-naïve and previously treated patients. Following a median follow-up of 11.6 months in 53 evaluable patients, Ayvakit achieved a 28% complete response rate, with an additional 28% of patients attaining a partial response. According to an analysis report by SVB Leerink, following its approval for the treatment of mastocytosis, Ayvakit's peak sales in the United States are projected to reach $737 million. Furthermore, potential expansion into the European market could unlock additional growth potential for the drug.

Source: NICE recommends Novartis’ Rydapt for AdvSM treatment