Mirdametinib NDA submitted to treat children, adults with NF1-PN


The submission to the FDA includes data from the phase 2b ReNeu trial of patients aged 2 years and older with NF1-associated PN causing significant morbidity.

Mirdametinib NDA submitted to treat children, adults with NF1-PN | Image Credit: © Araki Illustrations - © JAraki Illustrations - stock.adobe.com.

Mirdametinib NDA submitted to treat children, adults with NF1-PN | Image Credit: © Araki Illustrations - © JAraki Illustrations - stock.adobe.com.

According to a press release from SpringWorks Therapeutics, the company has submitted a New Drug Application (NDA) to the FDA for mirdametinib, an investigational MEK inhibitor, to treat neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) in adult and pediatric patients 2 years and older.1

The rare genetic disorder that stems from mutations in the NF1 gene is the most common form of neurofibromatosis. The estimated global birth incidence is 1 in 2500 individuals, with approximately 100,000 individuals living with NF1 in the United States. Abnormal pigmentation, skeletal deformities, tumor growth, and neurological complications are the variety of symptoms that can manifest in the clinical course of NF1.1

Those with NF1 have an 8-to-15-year mean reduction in life expectancy compared to the general population while carrying an approximate 30% to 50% lifetime risk of developing plexiform neurofibromas (PN), 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," stated SpringWorks in the press release.1

The FDA has granted Orphan Drug Designation to mirdametinib for the treatment of NF1, Fast Track Designation for the treatment of patients aged 2 years and older with NF1-PN that are progressing or causing "significant morbidity," and Rare Pediatric Disease Designation for the treatment of NF1.1

The oral, CNS-penetrant, allosteric small molecule MEK inhibitor is designed to inhibit MEK1 and MEK2, which occupy pivotal positions of the MAPK pathway, a key signaling network that regulates cell growth and survival.1

NDA submission is based on data from the phase 2b ReNeu trial (NCT03962543), an on-going, multi-center, open-label trial evaluating safety, efficacy, and tolerability of mirdametinib. The study enrolled 114 patients who received mirdametinib at a dose of 2 mg / m2 twice per day without regard to food (maximum dose of 4 mg twice per day). Administered orally in a 3-week on, 1-week off schedule, the primary endpoint of the trial is "confirmed objective response rate defined as ≥ 20% reduction in target tumor volume during the 24 cycle treatment phase, as measured by MRI and assessed by blinded independent central review," stated the company.1,2

Results, which were presented via oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting, demonstrated "significant objective response rates confirmed by blinded independent central review, deep and durable responses, improvement in pain and health-related quality of life as well as a manageable safety profile across both the adult and pediatric cohorts," SpringWorks stated.1

"We are pleased to be one step closer towards our goal of bringing mirdametinib to patients with NF1-PN in the U.S. and believe that our ReNeu data support the potential for mirdametinib to be a differentiated and best-in-class therapy for both children and adults living with this devastating disease," Saqib Islam, CEO of SpringWorks, said in a statement. "We look forward to working closely with the FDA throughout the review process and also plan to file for regulatory approval in the European Union later this year."1


  1. SpringWorks Therapeutics Completes Submission of New Drug Application to the FDA for Mirdametinib for the Treatment of Children and Adults with NF1-PN. SpringWorks Therapeutics. July 1, 2024. Accessed July 2, 2024. https://finance.yahoo.com/news/springworks-therapeutics-completes-submission-drug-103000295.html
  2. MEK Inhibitor Mirdametinib (PD-0325901) in Patients With Neurofibromatosis Type 1 Associated Plexiform Neurofibromas (ReNeu). ClinicalTrials.gov. Updated March 28, 2024. Accessed July 2, 2024. https://clinicaltrials.gov/study/NCT03962543

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