Mirdametinib is an oral, allosteric small molecule MEK inhibitor to treat pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN).
The FDA has accepted a new drug application (NDA) for mirdametinib (SpringWorks Therapeutics) for the treatment of adults and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN). Study authors noted that the NDA was granted priory review and was given a prescription drug user fee act action date for February 28, 2025. The company also announced the European Medicines Agency validated the marketing authorization application for mirdametinib. If approved, the investigation MEK inhibitor will be the first accepted therapy to treat NF1-PN among adults.1
NF1 is a rare genetic condition that stems from loss-of-function variants in the NF1 gene, impacting 1 in every 2500 people worldwide, with around 100,000 cases in the US. The disorder is the most common form of neurofibromatosis and individuals diagnosed with NF1 have an 8-to-15-year mean reduction in their life expectancy compared to the general population. Additionally, individuals with NF1 have a 30% to 50% lifetime risk of developing PN—which are tumors that grow along the peripheral nerve shaft causing pain and functional impairment.1 Due to their size, location, and invasiveness, PNs can also cause motor deficits and life-threatening complications.2 Study authors noted that the tumors grow quickly during childhood and are complicated to remove surgically because of its growing pattern along the nerves.1
“Plexiform neurofibromas may sit next to or surround vital organs and can cause serious medical complications for patients. While progress has been made, there remains a pressing need for more treatment options, particularly for adults who currently have no approved therapy,” Annette Bakker, PhD, CEO of the Children’s Tumor Foundation (CTF) and board chair of CTF Europe, said in a news release.1
According to the news release, mirdametinib is a potent, oral, CNS-penetrant, allosteric small molecule drug, intended to inhibit MEK1 and MEK2, that oppresses vital positions in the MAPK pathway. As a signaling network, MAPK controls cell growth and survival when genetically alerted, according to study authors.1
The submissions included data from the ongoing multi-center, open-label phase 2 ReNeu (NCT03962543) that assessed the efficacy, safety, and tolerability of mirdametinib among individuals older than 2 years with inoperable NF1-associated PN causing significant morbidity. The study included 114 individuals that received a 2mg/m2 dose of mirdametinib twice daily without food, in a 3-week on, 1-week off dosing schedule.1
Trial Name: MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas (ReNeu)
ClinicalTrials.gov ID: NCT03962543
Sponsor: SpringWorks Therapeutics Inc
Completion Date (Estimated): May 2025
The primary end point of the study is a confirmed objective response rate (ORR) with a greater than 20% reduction in target tumor volume on multiple scans during the 24-cycle treatment phase. The secondary end point includes safety and tolerability, duration of response, and changes in patient reported outcomes from baseline to cycle 13, according to study authors.1
Presented at the 2024 American Society of Clinical Oncology Annual Meeting, the results displayed significant ORR, confirmed by blinded independent central review, durable responses, improvement in pain and health-related quality of life, and controllable safety responses among adults and pediatric patients treated with mirdametinib.1
“These significant milestones bring us closer to our goal of delivering a transformative medicine to both adults and children with NF1-PN in the US and Europe,” Saqib Islam, CEO of SpringWorks, said in the news release. “People living with NF1-PN are in need of new advances and we look forward to working with the FDA and EMA during their review processes as we prepare to bring our second medicine to patients suffering from devastating diseases.”1
A long-term follow up of the study is currently ongoing among individuals that completed treatment and were eligible to continue to obtain mirdametinib.1
“CTF is dedicated to deploying its time, talent and funding towards accelerating the development of new treatments. We congratulate our long-term partner SpringWorks on this important milestone and we are thrilled that patients in the United States and Europe could soon have a new therapy available to them,” Bakker said in a news release.1
