SpringWorks Therapeutics receives positive CHMP Opinion for mirdametinib (Ezmekly) for the treatment of adult and pediatric patients with NF1-PN
SpringWorks Therapeutic Inc. announced the EMA’s 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. 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.
“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-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 IIb 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.
ReNeu (NCT03962543) is an ongoing, multi-center, open-label, single arm, Phase IIb 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) 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.
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.
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.
