SpringWorks Therapeutics, Inc., a healthcare company of Merck KGaA, Darmstadt, Germany, announced  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.