Selumetinib recently received approval from the U.S. Food and Drug Administration (FDA). This approval marks a significant development for individuals living with a rare genetic disorder.
Understanding Neurofibromatosis Type 1
Neurofibromatosis type 1 (NF1) is a genetic disorder affecting approximately one in 3,300 newborns. It arises from a mutation in the NF1 gene, which provides instructions for producing a protein called neurofibromin. Neurofibromin acts as a tumor suppressor, regulating cell growth and division. When the NF1 gene mutates, this regulatory control is lost, allowing cells to multiply unchecked.
A prominent feature of NF1 is the development of tumors known as plexiform neurofibromas (PNs). These tumors grow along nerves and can manifest anywhere in the body, including under the skin or deeper within the body. PNs can cause a range of issues such as pain, disfigurement, and functional impairment, depending on their size and location.
How Selumetinib Targets NF1
Selumetinib is an oral medication classified as a MEK inhibitor. It works by targeting a specific signaling pathway within cells known as the RAS/MAPK pathway. In NF1, the mutated NF1 gene leads to overactivity of this pathway, which promotes uncontrolled cell growth and tumor formation.
By selectively inhibiting MEK1 and MEK2 proteins within the RAS/MAPK cascade, selumetinib reduces this overactivity. This action aims to slow or stop the proliferation of cells that form plexiform neurofibromas, helping shrink these tumors and addressing the underlying cellular dysfunction in NF1.
The FDA Approval for Selumetinib
The U.S. Food and Drug Administration approved selumetinib (marketed as Koselugo) on April 10, 2020. This approval was specifically for pediatric patients, aged two years and older, who have neurofibromatosis type 1 with symptomatic, inoperable plexiform neurofibromas. This marked the first time a medication received FDA approval specifically for this condition.
The approval was largely based on the results of the SPRINT clinical trial. This open-label, single-arm, multicenter study involved 50 pediatric patients with inoperable PNs. The trial demonstrated that selumetinib led to a durable overall response rate, with 68% of children experiencing a reduction in tumor volume.
The SPRINT trial defined a partial response as a 20% or greater reduction in tumor volume, confirmed on subsequent imaging. Eighty-two percent of patients who responded maintained their response for at least 12 months. Selumetinib received several FDA designations, including Orphan Drug, Breakthrough Therapy, and Rare Pediatric Disease, recognizing the unmet medical need.
What This Means for Patients
The approval of selumetinib provides a significant new treatment option for children with NF1 and inoperable plexiform neurofibromas. For many years, surgical removal was the primary approach for these tumors, but it was often not feasible due to the tumors’ size, location, or entanglement with healthy nerves. The availability of an oral medication offers a non-surgical alternative.
Patients in the SPRINT trial experienced not only tumor shrinkage but also improvements in associated symptoms. These benefits included reduced pain, improved motor function, and enhanced quality of life. The most frequent side effects observed were generally manageable, including nausea, vomiting, diarrhea, skin rashes, and musculoskeletal pain.
Healthcare providers monitor patients closely to manage side effects. This approval offers a targeted therapy for a patient population that previously had limited medical options. It represents a significant step forward in managing NF1-related plexiform neurofibromas, potentially transforming the lives of affected children and their families.