SpringWorks Edges Closer to Landmark European Approval for NF1-PN Treatment
STAMFORD, Conn. — In a significant development for patients suffering from a rare genetic disorder, SpringWorks Therapeutics announced Sunday that its drug mirdametinib has received a positive recommendation from Europe's medical regulators, potentially establishing the first-ever treatment in the European Union for both adults and children with neurofibromatosis type 1 and its associated plexiform neurofibromas .
The Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed mirdametinib, an oral MEK inhibitor, for the treatment of symptomatic, inoperable plexiform neurofibromas in patients aged two years and older with NF1. The European Commission, which typically follows CHMP recommendations, is expected to make its final decision in the third quarter of this year.
"For the approximately 135,000 Europeans affected by NF1, this recommendation represents a watershed moment," said a leading medical expert familiar with the disease. "Until now, these patients—particularly adults—have faced extremely limited treatment options."
A Dual-Population Solution in a Fragmented Treatment Landscape
The potential approval would mark a strategic victory for SpringWorks in Europe's rare disease market. While AstraZeneca's selumetinib is available for pediatric patients in some regions, mirdametinib would be the first therapy approved for both children and adults with NF1-PN in the EU—a crucial distinction in a condition that affects patients across all age groups.
NF1 is characterized by tumors that grow along peripheral nerve sheaths in an infiltrative pattern, causing deformities, pain, and functional impairments. The tumors are notoriously difficult to remove surgically, with up to 85% considered unsuitable for complete resection, according to multiple clinical assessments.
"A surgical approach to plexiform neurofibromas can be extremely challenging and often impossible," said Dr. Ignacio Blanco, Chairman of the National Reference Center for Adult Patients with Neurofibromatosis at Hospital Universitari Germans Trias i Pujol in Spain. "If approved, mirdametinib could become an important treatment option for both pediatric and adult patients in Europe."
Compelling Efficacy Profile Drives Regulatory Support
The CHMP's positive opinion was based primarily on results from the ReNeu Phase 2b trial, which included 114 patients with NF1-PN aged two years or older. The study demonstrated objective response rates of 41% in adults and 52% in children, as determined by independent blinded central review.
What distinguishes these results is not just the tumor response rate but also the depth and durability of the response. The median best percentage change in targeted tumor volume was -41% in adults and -42% in children. Among responding patients, 88% of adults and 90% of children maintained their response for at least 12 months, with approximately half still responding at the 24-month mark.
Patients experienced early and sustained improvements in pain and quality of life compared to baseline—critical outcomes in a disease known for its significant impact on daily functioning.
Comparing the Competitive Landscape
Market analysis suggests mirdametinib's profile may provide meaningful differentiation from existing therapies. While selumetinib showed a 66% response rate in children in its pivotal SPRINT Phase II trial, its performance in adults—with a 19.7% response rate versus 5.4% for placebo in the KOMET Phase III study—appears less robust than mirdametinib's 41% in adults from ReNeu.
Healthcare analysts note that mirdametinib's dosing regimen—three weeks on, one week off—could potentially enhance tolerability compared to continuous twice-daily dosing required by some alternatives. Additionally, if approved, the drug would be available as both standard capsules and a water-soluble tablet formulation, potentially improving adherence, particularly among younger patients.
"The intermittent dosing schedule combined with flexible formulation options addresses some key challenges in managing this chronic condition," noted one pharmaceutical consultant who specializes in rare diseases. "These seemingly minor differences can significantly impact real-world treatment success."
Significant Market Opportunity Amid Growing Corporate Interest
The positive CHMP opinion comes at a pivotal time for SpringWorks. The global NF1-PN treatment market, valued at approximately $1.45 billion in 2024, is projected to reach $2.74 billion by 2032, growing at a compound annual rate of 8.3%.
Industry forecasts suggest mirdametinib could achieve peak annual sales of approximately $470 million by 2028, representing a substantial revenue opportunity for a company that reported total product revenue of $49 million in the first quarter of 2025 ($44.1 million from OGSIVEO and $4.9 million from GOMEKLI).
This market potential hasn't gone unnoticed. German pharmaceutical company Merck KGaA recently agreed to acquire SpringWorks for $3.9 billion ($47 per share), representing a premium of approximately 26% over the company's pre-announcement share price. The acquisition is expected to be earnings-accretive for Merck by 2027, underscoring the strategic value of SpringWorks' rare disease and oncology portfolio.
Navigating European Market Access Challenges
Despite the promising clinical profile, industry observers identify several potential hurdles to widespread adoption. Identifying and directing rare NF1-PN patients to specialized treatment centers remains logistically challenging. Additionally, the safety profile, while manageable, includes MEK inhibitor class-related adverse events that require monitoring.
The most common adverse reactions in adults included rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue. In children, these included rash, diarrhea, musculoskeletal pain, vomiting, headache, paronychia, left ventricular dysfunction, and nausea.
European pricing and reimbursement negotiations will also be critical. With orphan drugs typically commanding premium prices—selumetinib lists at approximately $12,500 per month in the U.S.—SpringWorks faces the challenge of navigating diverse health technology assessment processes across European markets.
"Early engagement with key HTA bodies like Germany's G-BA, France's HAS, and the UK's NICE will be essential," explained a market access specialist. "European payers increasingly demand robust real-world evidence to confirm long-term value, particularly for high-cost orphan therapies."
The Path Forward: Integration and Expansion
As SpringWorks awaits the European Commission's final decision, the company must simultaneously prepare its launch infrastructure and navigate the integration process with Merck KGaA. Industry insiders suggest the company will need to establish regional distribution networks, specialty pharmacy agreements, and comprehensive medical education programs.
Looking beyond the initial approval, experts anticipate potential label expansion efforts to explore additional NF1 manifestations or combination regimens that could further cement mirdametinib's position in the treatment landscape.
For patients like 23-year-old Sophia M. from Berlin, who has lived with painful neurofibromas since childhood, these developments represent more than corporate milestones.
"Every day with this condition is unpredictable," she said during a recent patient advocacy meeting. "The possibility of a treatment that could shrink these tumors and reduce pain would change everything."
For the thousands of European NF1-PN patients currently managing their condition with limited options, the European Commission's upcoming decision could mark the beginning of a new treatment era—one where both children and adults have access to therapies specifically designed to address their needs.