Understanding Neurofibromatosis Type 1 (NF1)
Neurofibromatosis type 1 (NF1) is a complex genetic condition caused by a mutation in the NF1 gene [1.5.4]. This gene is responsible for producing neurofibromin, a protein that helps regulate cell growth. When this protein is faulty, it can lead to uncontrolled cell growth, resulting in tumors along nerves [1.5.7]. One of the most common manifestations is the plexiform neurofibroma (PN), a benign but often debilitating tumor that grows along nerve sheaths and can cause pain, disfigurement, and functional impairment [1.4.3, 1.5.7]. Historically, treatment for inoperable PNs was limited, often involving a "watch and wait" approach or risky surgeries [1.5.1]. The development of targeted therapies has created a paradigm shift in managing this condition [1.5.4].
The Newest Breakthrough: Mirdametinib (Gomekli)
The most significant recent development in NF1 treatment is the FDA's approval of mirdametinib (brand name Gomekli) on February 11, 2025 [1.2.1]. This approval makes mirdametinib the newest drug available for NF1. It is indicated for both adult and pediatric patients aged 2 years and older who have symptomatic, inoperable plexiform neurofibromas [1.5.6]. This makes it the first approved therapy for adults with this condition, a milestone for a patient population that previously had no FDA-approved drug therapies [1.5.1].
How MEK Inhibitors Work
Both mirdametinib and the previously approved selumetinib belong to a class of drugs called MEK inhibitors [1.4.3]. They work by targeting the RAS/MAPK signaling pathway, a key network that regulates cell growth and survival [1.5.2, 1.5.4]. In individuals with NF1, this pathway is overactive, driving the growth of tumors [1.4.2]. MEK inhibitors block specific enzymes (MEK1 and MEK2) within this pathway, thereby slowing down or stopping the proliferation of tumor cells and shrinking the neurofibromas [1.3.6, 1.4.2].
Mirdametinib's Clinical Success
The approval of mirdametinib was based on the pivotal Phase 2b ReNeu trial, which demonstrated significant efficacy and a manageable safety profile [1.5.1, 1.5.2]. In the trial:
- Objective Response Rate (ORR): 41% of adult patients and 52% of pediatric patients showed a confirmed objective response, meaning their tumors shrank by at least 20% in volume [1.2.1].
- Durable Responses: Many patients experienced deep and durable tumor volume reductions, with median best responses showing a volume reduction of -41% in adults and -42% in children [1.5.1].
- Improved Quality of Life: Patients in both cohorts reported significant and clinically meaningful improvements in tumor pain severity, pain interference, and overall health-related quality of life [1.5.1].
The First Approved Drug: Selumetinib (Koselugo)
Before mirdametinib, selumetinib (brand name Koselugo) was the first-ever drug approved by the FDA for NF1, receiving its initial approval in April 2020 for pediatric patients aged 2 and older [1.3.3, 1.3.4]. Its approval was a landmark achievement, proving that MEK inhibition was a viable strategy [1.4.1]. In September 2025, its approval was expanded to include children as young as 1 year old, opening the door for earlier intervention [1.3.1, 1.2.5]. Clinical trials showed that over 70% of pediatric patients treated with selumetinib experienced tumor size reduction between 20-60% [1.3.1].
Comparison: Mirdametinib vs. Selumetinib
While both drugs are MEK inhibitors, there are key distinctions.
| Feature | Mirdametinib (Gomekli) | Selumetinib (Koselugo) |
|---|---|---|
| FDA Approval Date | February 11, 2025 [1.2.1] | April 10, 2020 (initial); Expanded Sept. 10, 2025 [1.3.3, 1.3.2] |
| Approved Patient Population | Adults and children (2 years and older) [1.5.6] | Children (1 year and older) [1.3.2] |
| Administration | Capsules or tablets for oral suspension; can be taken with or without food [1.5.1, 1.5.3]. | Capsules that must be taken on an empty stomach (no food 2 hours before or 1 hour after) [1.3.6]. |
| Efficacy (Pediatric ORR) | 52% confirmed ORR in the ReNeu trial [1.2.1]. | 66% ORR in its pivotal trial [1.3.8]. An indirect comparison suggested mirdametinib had a greater mean reduction in tumor volume [1.5.9]. |
| Common Side Effects | Rash, diarrhea, nausea, musculoskeletal pain, vomiting, fatigue [1.2.1]. | Vomiting, rash, abdominal pain, diarrhea, nausea, fatigue, musculoskeletal pain [1.3.6]. |
The Future of NF1 Pharmacology
The arrival of mirdametinib and selumetinib signals a new era for NF1 treatment. Research continues to expand, with the number of NF clinical trials tripling in the last decade [1.6.1]. Initiatives like platform trials are being developed to test multiple drugs in parallel, aiming to accelerate the discovery of new treatments for different manifestations of NF1, including plexiform neurofibromas, cutaneous neurofibromas, and optic pathway gliomas [1.6.1, 1.6.3]. Researchers are also exploring other drugs like cabozantinib in clinical trials [1.6.2].
Conclusion
The question 'What is the new drug for NF1?' is answered with the 2025 approval of mirdametinib (Gomekli), a significant advancement that provides the first approved therapy for adults with inoperable PNs and a second powerful option for children. It builds on the success of selumetinib (Koselugo), and together these MEK inhibitors have fundamentally changed the treatment landscape from passive monitoring to active, targeted therapy. The robust pipeline of clinical trials offers continued hope for even more effective treatments for the entire NF community. For more information on clinical trials, one authoritative resource is the U.S. National Library of Medicine's database at ClinicalTrials.gov [1.6.9].
