Mirdametinib

– EZMEKLY is the first and only therapy to receive marketing authorization in the EU for both adults and children (≥2 years) with NF1-PN, a rare genetic disorder with debilitating symptoms – STAMFORD, CT, USA I July 18, 2025 I SpringWorks Therapeutics, Inc., a healthcare company of Merck, announced today that the European Commission (EC) granted conditional marketing authorization for EZMEKLY ® (mirdametinib) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in pediatric and adult patients with neurofibromatosis type 1 (NF1) aged 2 years and above. EZMEKLY is the first and only therapy approved in the European Union (EU) for both adults and children with NF1-PN. “Patients with NF1-PN often face physical and mental health challenges and impaired quality of life given the limited treatment options available for this lifelong and debilitating disease,” said Ignacio Blanco, MD, PhD, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol, Spain. “This approval represents an important advance, especially for adults who previously did not have an approved treatment. In clinical trials, EZMEKLY demonstrated an encouraging efficacy and safety profile in both adults and children, and importantly, is available in a tablet that dissolves easily in water for people who are unable to swallow a pill and could therefore not previously receive therapy.” “This European Commission approval is an important milestone for NF patients and caregivers, as it means more treatment options for patients with plexiform neurofibromas, including adults,” said Annette Bakker, PhD, Chief Executive Officer of the Children’s Tumor Foundation (CTF) and Dariusz Adamczewski, MD, Director CTF Europe. “This is the kind of progress that happens when researchers, industry and organizations like ours work together with a shared focus on delivering new treatments for patients.” NF1 is a genetic disorder that affects approximately 3 in 10,000 people in the EU, or an estimated 135,000 people. 1,2 Among patients with NF1, the lifetime risk of developing plexiform neurofibromas is approximately 30% to 50%. These tumors grow in an infiltrative pattern along the peripheral nerve sheath and 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 “Bringing innovation to patients living with rare tumors around the world is a clear reflection of our focus on addressing significant unmet needs and transforming outcomes for patients and their families,” said Jan Kirsten, Global Head of Rare Tumor Business. “With the European approval of EZMEKLY, the first therapy approved for both adults and children with NF1-PN, we are taking a major step toward improving care for this underserved community and are committed to making our medicine available to eligible NF1-PN patients across Europe as quickly as possible.” The EC approval of EZMEKLY is based on results from the ongoing, multi-center, open-label, single arm 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 EZMEKLY demonstrated a manageable safety and tolerability profile. The most common adverse reactions reported in adults receiving EZMEKLY were dermatitis acneiform (83%), diarrhea (55%), nausea (55%), blood creatine phosphokinase increased (47%), musculoskeletal pain (41%), vomiting (37%) and fatigue (36%). The most common adverse reactions occurring in children were blood creatine phosphokinase increased (59%), diarrhea (53%), dermatitis acneiform (43%), musculoskeletal pain (41%), abdominal pain (40%), vomiting (40%), and headache (36%). 9 EZMEKLY is available in 1 and 2 mg capsules and in a 1 mg dispersible tablet, which dissolves easily in water. 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/m 2 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. 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 Patients with NF have approximately a 30% to 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 GOMEKLI ® / EZMEKLY ® (mirdametinib) GOMEKLI ® (mirdametinib) is an oral, small molecule MEK inhibitor approved by the U.S. Food and Drug Administration (FDA) 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. Mirdametinib is marketed under the brand name EZMEKLY ® in the European Union and is conditionally approved by the European Commission (EC) 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 FDA and the EC have granted Orphan Drug designation for mirdametinib for the treatment of NF1. For the full list of side effects and restrictions with EZMEKLY, see the full Summary of Product Characteristics . IMPORTANT SAFETY INFORMATION Ocular toxicity Patients should be advised to report any new visual disturbances. RVO (retinal vein occlusion) and RPED (retinal pigment epithelial detachment) were commonly reported in adult patients receiving Ezmekly in clinical studies. A comprehensive ophthalmological evaluation prior to treatment initiation, at regular intervals during treatment, and at any time a patient reports new or worsening visual changes such as blurred vision is necessary in children, adolescents and adults. For ocular adverse reactions, Ezmekly therapy should be interrupted and then dose reduced or treatment permanently discontinued based on severity of the adverse reaction. If RVO is diagnosed, treatment with Ezmekly should be permanently discontinued. If symptomatic RPED is diagnosed, treatment with Ezmekly should be interrupted until resolution and the dose reduced when treatment is resumed. In patients diagnosed with RPED without reduced visual acuity, treatment can be continued but ophthalmic assessment should be conducted every 3 weeks until resolution. Decreased left ventricular ejection fraction (LVEF) Asymptomatic decrease in LVEF ≥ 10% from baseline occurred in 17% of adult patients and 27% of paediatric patients in the ReNeu study. All cases of decreased LVEF in adult or paediatric patients in the clinical studies were asymptomatic. Patients with a history of impaired LVEF or a baseline ejection fraction that is below the institutional lower limit of normal (LLN) have not been studied. LVEF should be evaluated by echocardiogram before initiation of treatment to establish baseline values, every 3 months during the first year, then as clinically indicated thereafter. Prior to starting treatment, patients should have an ejection fraction above the institutional LLN. Decreased LVEF can be managed using treatment interruption, dose reduction or treatment discontinuation. Skin toxicity Skin adverse reactions, including rash (dermatitis acneiform and non‑acneiform rashes), dry skin, pruritus, eczema, and hair changes have been reported in the ReNeu study. Patients should contact their doctor or nurse if they experience any skin reactions. Supportive care, e.g. the use of emollient creams, should be initiated at first signs of skin toxicity. Ezmekly therapy should be interrupted, the dose reduced or permanently discontinued based on severity of the adverse reaction. Carcinogenicity risk A potential carcinogenicity risk in humans could not be excluded at the clinical exposure range. Women of childbearing potential/Contraception in females and males Ezmekly is not recommended in women of childbearing potential who are not using contraception. Both male and female patients (of reproductive potential) should be advised to use effective contraception. About SpringWorks Therapeutics SpringWorks Therapeutics, a healthcare company of Merck, is a commercial-stage biopharmaceutical company dedicated to improving the lives of patients with rare tumors. We developed and are commercializing the first and only FDA-approved medicine for adults with desmoid tumors and the first and only approved medicine for both adults and children with neurofibromatosis type 1 associated plexiform neurofibromas (NF1-PN). We are also advancing a portfolio of novel targeted therapy product candidates for patients with additional rare tumors and hematological cancers. For more information, visit www.springworkstx.com and follow @SpringWorksTx on X, LinkedIn , Facebook , Instagram and YouTube . About Merck Merck, a leading science and technology company, operates across life science, healthcare and electronics. More than 62,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From providing products and services that accelerate drug development and manufacturing as well as discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2024, Merck generated sales of € 21.2 billion in 65 countries. Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as MilliporeSigma in life science, EMD Serono in healthcare, and EMD Electronics in electronics. 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The European Commission has conditionally approved Ezmekly (mirdametinib) as a treatment for inoperable, symptomatic plexiform neurofibromas (PN) in paediatric and adult patients with neurofibromatosis type 1 (NF1) aged two and older. The oral MEK inhibitor was developed by SpringWorks Therapeutics before its recent $3.9-billion takeout by Merck KGaA.The approval, which follows backing by the EU's drug advisory panel in May, is supported by results from the single-arm Phase IIb ReNeu trial. In the study, which included 58 adults and 56 children with NF1-PN, the drug shrank target tumours by at least 20% in 41% of adults and 52% of children. The median best percentage change in target PN volume was -41% in adults and -42% in children.Among responders, 88% of adults and 90% of children sustained their response for at least 12 months, with roughly half maintaining benefit for two years or longer."With the European approval of Ezmekly, the first therapy approved for both adults and children with NF1-PN, we are taking a major step toward improving care for this underserved community," said Jan Kirsten, global head of Merck's rare tumour business, in a release Friday.Ezmekly was approved earlier this year in the US under the brand name Gomekli. It's SpringWorks' second marketed drug, joining oral gamma secretase inhibitor Ogsiveo (nirogacestat), which was approved in 2023 for desmoid tumours.