On May 23, 2025 SpringWorks Therapeutics, Inc. (Nasdaq: SWTX), a commercial-stage biopharmaceutical company focused on severe rare diseases and cancer, reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion recommending the granting of a conditional marketing authorization for mirdametinib, a MEK inhibitor, for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above (Press release, SpringWorks Therapeutics, MAY 23, 2025, View Source [SID1234653361]). The European Commission (EC) will review the CHMP opinion and is expected to make a final decision regarding the approval in the third quarter of 2025. If approved, mirdametinib will be available in 1 and 2 mg capsules and in a 1 mg dispersible tablet, which dissolves easily in water.
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"The positive opinion from the CHMP brings us one step closer to delivering our medicine to both children and adults with NF1-PN in Europe, who we believe are in need of new therapeutic advances," said Saqib Islam, Chief Executive Officer of SpringWorks. "Upon approval, we look forward to bringing mirdametinib to appropriate patients in Europe as quickly as possible."
NF1 is a genetic disorder that affects approximately 3 in 10,000 people in the EU, or an estimated 135,000 people.1,2 Patients with NF1 have approximately a 30 to 50% lifetime risk of developing plexiform neurofibromas, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment.3,4 Plexiform neurofibromas can transform into malignant peripheral nerve sheath tumors, an aggressive and potentially fatal disease.5 Surgical removal can be challenging due to the infiltrative tumor growth pattern of plexiform neurofibromas along nerves, and up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8
"NF1-PN is a genetic disorder that can be highly morbid and unpredictable. It takes a significant physical and emotional toll on patients and their caregivers, and there have been limited treatment options available," said Ignacio Blanco, MD, PhD, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol, Spain. "Surgical removal of plexiform neurofibromas can be challenging and is often not possible, so if approved, mirdametinib could be an important treatment option for children and adult patients in Europe."
The CHMP opinion was based on the Marketing Authorization Application (MAA) for mirdametinib, which was validated by the EMA in August 2024. The MAA centered on the primary results from the Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN age 2 years or older (58 adults and 56 pediatric patients). The study met the primary endpoint of confirmed objective response rate (ORR), as assessed by blinded independent central review, demonstrating an ORR of 41% (N= 24/58) in adults and 52% in children (N=29/56). The median best percentage change in target PN volume was -41% (range: -90 to 13%) in adults and -42% (range: -91 to 48%) in children. Among those with a confirmed response, 88% percent of adults and 90% of children had a response of at least 12 months duration, and 50% and 48%, respectively, had a response of at least 24 months duration. Both adults and children also experienced early and sustained significant improvements from baseline in pain and quality of life as assessed across multiple patient-reported outcome tools.9
Mirdametinib demonstrated a manageable safety and tolerability profile. The most common adverse events (>25%) reported in adults receiving mirdametinib were rash, diarrhea, nausea, musculoskeletal pain, vomiting and fatigue. The most common adverse events (>25%) occurring in children were rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction and nausea.9
Mirdametinib is approved in the U.S. for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
About the ReNeu Trial
ReNeu (NCT03962543) is an ongoing, multi-center, open-label, single arm, Phase 2b trial evaluating the efficacy, safety and tolerability of mirdametinib in patients ≥2 years of age with an inoperable NF1-associated PN causing significant morbidity. The study enrolled 114 patients to receive mirdametinib at a dose of 2 mg/m2 twice daily (maximum dose of 4 mg twice daily) without regard to food. Mirdametinib was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet. The primary endpoint is confirmed objective response rate (ORR) defined as the proportion of patients with a ≥20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by MRI and assessed by blinded independent central review. Secondary endpoints include safety and tolerability, duration of response, and changes in patient-reported outcomes from baseline to Cycle 13. The treatment phase of the trial is complete, and results were presented at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Patients who completed the treatment phase were eligible to continue receiving treatment in the optional long-term follow-up portion of the study, which is ongoing.
About NF1-PN
Neurofibromatosis type 1 (NF1) is a rare genetic disorder that arises from mutations in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway.10,11 NF1 is the most common form of neurofibromatosis, with an estimated global birth incidence of approximately 1 in 2,500 individuals.3,12 In the EU, NF1 affects approximately 3 in 10,000 people, or an estimated 135,000 people.1,2 The clinical course of NF1 is heterogeneous and manifests in a variety of symptoms across numerous organ systems, including abnormal pigmentation, skeletal deformities, tumor growth and neurological complications, such as cognitive impairment.13 Patients with NF1 have an 8 to 15-year mean reduction in their life expectancy compared to the general population.1
NF patients have approximately a 30%-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal.3,4,5 NF1-PNs are most often diagnosed in the first two decades of life.3 These tumors can be aggressive and are associated with clinically significant morbidities; typically, they grow more rapidly during childhood.14,15
Surgical removal of these tumors can be challenging due to the infiltrative tumor growth pattern along nerves and can lead to permanent nerve damage and disfigurement.5 Up to approximately 85% of plexiform neurofibromas are considered not amenable to complete resection.6,7,8
About Mirdametinib
Mirdametinib is an oral, small molecule MEK inhibitor approved in the United States for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
The FDA and the European Commission have granted Orphan Drug designation for mirdametinib for the treatment of NF1.