For many years, the primary treatments for neurofibromatosis (NF) focused on managing symptoms through surgery and other supportive care. The landscape has evolved significantly with the approval of targeted therapies, particularly for neurofibromatosis type 1 (NF1), the most common form. This guide explores the leading pharmacological options, focusing on MEK inhibitors, and outlines other essential components of a comprehensive treatment plan.
The Rise of MEK Inhibitors in Neurofibromatosis Treatment
NF1 is caused by a genetic mutation that results in an overactive cellular signaling pathway, known as the RAS/RAF/MEK pathway, which promotes uncontrolled cell growth and tumor formation. MEK inhibitors are a class of medications designed to block this pathway, thereby slowing or stopping the growth of certain tumors. This has been a transformative development, offering a systemic treatment for inoperable tumors that were previously managed with limited success.
FDA-Approved MEK Inhibitors
Two MEK inhibitors have received FDA approval for treating inoperable plexiform neurofibromas (PNs), a major manifestation of NF1. PNs are complex tumors that grow along nerves and can cause pain, disfigurement, and organ compression.
- Selumetinib (Koselugo): Approved in 2020 for pediatric patients with NF1 and symptomatic, inoperable PNs. The FDA expanded its approval in September 2025 to include children as young as one year old. Clinical trials demonstrated significant tumor shrinkage in a majority of patients, leading to reduced pain and improved physical function. Selumetinib is a standard of care for this patient population.
- Mirdametinib (Gomekli): Approved in February 2025 for adults and pediatric patients aged 2 years and older with NF1 and inoperable PNs. Its approval, based on clinical trial data, showed meaningful decreases in tumor volume, providing a new option for patients, including adults who were not covered by earlier approvals.
Both drugs represent a major step forward, but they are not cures. They are used to manage tumor growth and related symptoms, often requiring long-term treatment and regular monitoring for side effects, which can include rash, gastrointestinal issues, and fatigue.
Symptomatic and Supportive Therapies
While MEK inhibitors address the underlying cause of certain tumors, a comprehensive treatment plan for NF often involves managing a wide range of associated symptoms and complications.
Pain Management
Chronic pain is a common issue for NF patients, especially those with PNs. While MEK inhibitors have shown great promise in alleviating neuropathic pain by shrinking tumors, other strategies are often necessary.
- Neuropathic Pain Medication: For pain that persists or is not fully relieved by MEK inhibitors, specific medications for nerve pain may be prescribed.
- Analgesics: Over-the-counter or prescription pain relievers can manage general discomfort.
- Physical Therapy: Can improve mobility and reduce pain associated with skeletal changes or muscle weakness.
- Psychological Support: Counseling and support groups help patients cope with chronic pain and its emotional impact.
Surgery and Radiation
For certain tumors, surgical removal remains a viable option. This is typically recommended for tumors that are resectable and causing significant problems. Radiation therapy may also be used in some malignant cases.
Cognitive and Developmental Interventions
Many NF1 patients, particularly children, experience learning disabilities, attention deficit hyperactivity disorder (ADHD), and other cognitive issues.
- Educational Support: Specialized learning programs and school accommodations can help children succeed.
- Behavioral Therapy: Can address behavioral issues and improve social skills.
- Medication: Stimulant medications like methylphenidate may be used to treat ADHD symptoms in children with NF1.
Comparison of Approved MEK Inhibitors
| Feature | Selumetinib (Koselugo) | Mirdametinib (Gomekli) |
|---|---|---|
| Indication | NF1 with symptomatic, inoperable plexiform neurofibromas (PN) | NF1 with symptomatic, inoperable plexiform neurofibromas (PN) |
| Approved Age | Pediatric patients starting at 1 year of age | Adults and pediatric patients 2 years of age and older |
| FDA Approval | First approved in April 2020 (children 2+), expanded in September 2025 (children 1+) | Approved in February 2025 |
| Mechanism | MEK1 and MEK2 kinase inhibitor | MEK inhibitor |
| Administration | Oral capsules or oral granules | Oral administration |
| Clinical Efficacy | Significant and sustained tumor volume reduction (70%+ response in trials) | Significant tumor volume reduction and symptom improvement |
| Pain Reduction | Shown to effectively reduce neuropathic pain | Reports of reduced pain and improved function in clinical trials |
The Role of Clinical Trials in Future Treatments
Research into new NF treatments is robust, with numerous ongoing clinical trials exploring novel therapies. These studies are crucial for expanding treatment options beyond the current MEK inhibitors and for addressing other NF-related complications.
- New MEK Inhibitors: Other MEK inhibitors, like binimetinib, are being investigated for NF1-associated tumors.
- Combination Therapies: Researchers are exploring combination therapies, including combining MEK inhibitors with other targeted agents, to improve efficacy or reduce side effects.
- Genetic and Targeted Therapies: For example, Healx is advancing an AI-driven drug candidate, HLX-1502, which has received FDA Fast Track designation.
- Cutaneous Neurofibromas: Trials for topical treatments are underway to address the cosmetic and discomfort issues of skin tumors.
Conclusion: A Personalized Approach to Treatment
Deciding on the best medication for neurofibromatosis is a decision made in close consultation with a specialized medical team. There is no one-size-fits-all answer, as the ideal treatment depends on the specific subtype of NF, the nature of the tumors (location, size, operability), the patient's age, and the severity of symptoms. While MEK inhibitors have established themselves as the first effective systemic therapy for inoperable plexiform neurofibromas, they are part of a broader, personalized care strategy. This strategy includes managing associated symptoms with supportive therapies and staying informed about cutting-edge developments through clinical trials. Patients are encouraged to work with their doctors to create a comprehensive treatment plan tailored to their unique needs.
Find a specialist in your area through the Children's Tumor Foundation.
