FDA approves selumetinib for children with NF1 and inoperable tumors

The U.S. Food and Drug Administration has approved granular and capsule forms of selumetinib for the treatment of pediatric patients younger than 1 year of age with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas. This marks an expansion of the drug's previous approval, which was limited to children 2 years and older, expanding treatment opportunities for younger patients facing this rare and challenging disease.

Preclinical studies have determined that The loss of neurofibromin in NF1 activates the RAS/MEK/ERK signaling pathway and promotes tumor cell proliferation and growth. By blocking MEK, selumetinib directly targets this pathway and slows or prevents tumor progression in patients with NF1-related plexiform neurofibromas. The clinical availability of MEK inhibitors has changed the treatment landscape, providing physicians with a non-surgical option to address previously untreatable disease. Using selumetinib, clinicians can intervene earlier in the disease course to reduce tumor burden, manage debilitating symptoms, and improve long-term prognosis and quality of life in children with NF1.

On April 10, 2020, the U.S. Food and Drug Administration approved selumetinib for the first time in pediatric patients 2 years and older with NF1 and symptomatic, inoperable plexiform neurofibromas, marking the first treatment for this rare and debilitating disease. 3 The approval is based on results from the National Cancer Institute (NCI)-sponsored SPRINT (NCT01362803) trial, which demonstrated an overall response rate of 66% (n = 33; 95% CI, 51%-79%), as assessed by the NCI, with most responses lasting at least 12 months.

Patients experience improvement in conditions such as disfigurement, motor dysfunction, pain, airway or vision impairment. Safety study results are consistent with the drug's kinase inhibitor mechanism, and common adverse reactions include gastrointestinal and skin toxicity, as well as the risk of cardiomyopathy and ocular complications.

The FDA's new approval of selumetinib expands use of the therapy to children younger than 1 year of age with NF1 and symptomatic, inoperable plexiform neurofibromas, supported by bridging data between capsule and oral granule formulations. A bioavailability study in healthy adults and exposure-matched results from the SPRINT and SPRINKLE (NCT05309668) trials confirmed similar drug exposures, allowing extrapolation of efficacy data from older patients to younger children.

The updated prescribing information includes expanded safety data that reiterate known risks such as cardiomyopathy, ocular and gastrointestinal toxicity, skin reactions, and increased risk of bleeding, although no new safety signals were observed. The recommended dose is 25 mg/m2 twice daily until disease progression or unacceptable toxicity.

References:https://www.ajmc.com/view/fda-approves-selumetinib-for-children-with-nf1-and-inoperable-tumors