Mirdametinib Earns Positive CHMP Opinion for NF1-Associated Plexiform Neurofibromas

NF1-PN | Image Credit:
© Sebastian Kaulitzki
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The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for the oral, small molecule MEK inhibitor mirdametinib (Gomekli) for the treatment of adult and pediatric patients at least 2 years of age with symptomatic, inoperable neurofibromatosis type 1–associated plexiform neurofibromas (NF1-PN).1

According to SpringWorks Therapeutics, the drug’s developer, the European Commission (EC) is expected to review this opinion and issue a final verdict on the approval of mirdametinib in the third quarter of 2025. If approved, mirdametinib will be available as 1-mg and 2-mg capsules, as well as a 1-mg dispersible tablet formulation that dissolves 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,” Saqib Islam, chief executive officer of SpringWorks Therapeutics, stated in a news release. “Upon approval, we look forward to bringing mirdametinib to appropriate patients in Europe as quickly as possible.”

The CHMP recommendation was supported by a marketing authorization application submitted to the EMA in August 2024, which featured primary findings from the phase 2b ReNeu trial (NCT03962543). In this study, mirdametinib demonstrated a confirmed overall response rate (ORR) of 41% (95% CI, 29%-55%) in adult patients (n = 58) and 52% (95% CI, 38%-65%) in pediatric patients (n = 56), per blinded independent central review. The median best percentage reduction in target PN volume was –41% (range, –90% to 13%) in adult patients and –42% (range, –91% to 48%) in pediatric patients.

Among confirmed responders, the 12-month duration of response (DOR) rate was 88% in adult patients and 90% in pediatric patients; the 24-month DOR rates were 50% and 48%, respectively. Improvements in pain and quality of life were observed early and sustained, based on multiple patient-reported outcome measures.

Mirdametinib had a manageable safety profile and was deemed tolerable. In adult patients, the most common adverse effects (AEs) reported in at least 25% of patients included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. Among pediatric patients, frequent AEs included rash, diarrhea, musculoskeletal pain, abdominal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.

Results from ReNeu also provided the basis for the February 2025 FDA approval of mirdametinib for adult and pediatric patients 2 years of age and older with NF1 who have symptomatic PN not amenable to complete resection.2

ReNeu is an ongoing, multicenter, open-label, single-arm phase 2b trial evaluating the efficacy, safety, and tolerability of mirdametinib in patients 2 years of age or older with inoperable NF1-PN associated with significant morbidity.1

A total of 114 patients with NF1-PN were enrolled onto the study, who all received mirdametinib either as capsules or dispersible tablets at 2 mg/m² twice daily, with a maximum dose of 4 mg twice daily, on a 3-week-on/1-week-off schedule.

The trial's primary end point was confirmed ORR, defined as a 20% or greater reduction in target tumor volume on MRI across consecutive scans during the 24-cycle treatment period. Secondary end points included safety, DOR, and changes in patient-reported outcomes through Cycle 13.

The treatment phase of ReNeu is complete, and updated findings were previously presented at the 2024 ASCO Annual Meeting. An optional long-term follow-up phase is ongoing.

“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,” Ignacio Blanco, MD, PhD, chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias in Pujol, Spain, added in the news release. “Surgical removal of PNs 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.”

References

1. SpringWorks Therapeutics receives positive CHMP opinion for mirdametinib for the treatment of adult and pediatric patients with NF1-PN. News release. SpringWorks Therapeutics. May 23, 2025. Accessed May 23, 2025. https://ir.springworkstx.com/news-releases/news-release-details/springworks-therapeutics-receives-positive-chmp-opinion
2. FDA approves mirdametinib for adult and pediatric patients with neurofibromatosis type 1 who have symptomatic plexiform neurofibromas not amenable to complete resection. FDA. February 11, 2025. Accessed May 23, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-mirdametinib-adult-and-pediatric-patients-neurofibromatosis-type-1-who-have-symptomatic