By Counterforce Health Team —

Understanding Koselugo (Selumetinib): A Targeted Therapy for Neurofibromatosis Type 1

For families affected by neurofibromatosis type 1 (NF1), managing the complications of this rare genetic condition can be challenging — especially when tumors cause pain, disfigurement, or functional problems.

In 2020, the U.S. Food and Drug Administration (FDA) approved Koselugo® (selumetinib) — the first medication specifically developed to treat certain tumors associated with NF1. This approval marked a major milestone in the care of children with this condition.

What Is Koselugo?

Koselugo (selumetinib) is an oral prescription medication used to treat children aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PNs) — benign tumors that grow along nerves and can cause pain, deformity, or compression of nearby organs.

Koselugo belongs to a class of targeted therapies known as MEK inhibitors. It is taken by mouth as capsules, usually twice daily.

Understanding NF1 and Plexiform Neurofibromas

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by a mutation in the NF1 gene, which normally helps regulate cell growth. When this gene doesn’t function properly, cells can grow uncontrollably, leading to benign tumors on nerves called neurofibromas.

Some patients develop large, complex tumors called plexiform neurofibromas. These can grow deep in the body, press on vital structures, and may be difficult or impossible to remove surgically.

Before Koselugo, treatment options were largely limited to surgery or symptom management. Koselugo offered the first non-surgical, systemic therapy option shown to shrink these tumors.

How Koselugo Works

Koselugo is a MEK 1/2 inhibitor — it blocks a protein in the RAS/MAPK signaling pathway, which is overactive in people with NF1.

By blocking this pathway, Koselugo can help:

  • Slow or stop tumor cell growth
  • Shrink plexiform neurofibromas in some patients
  • Relieve symptoms such as pain or functional impairment

The medication doesn’t cure NF1 or eliminate all tumors, but it can significantly reduce the size of tumors and improve quality of life for many children.

Clinical Evidence and FDA Approval

Koselugo was approved based on a clinical trial of 50 children with NF1 and inoperable plexiform neurofibromas.

Key findings from the study:

  • 68% of patients experienced a confirmed partial tumor response, meaning their tumors shrank by at least 20%.
  • Many of those responses were durable — lasting one year or longer.
  • Patients also showed improvement in pain, mobility, and daily functioning.

This was the first evidence that a medication could significantly reduce tumor burden in NF1, changing the standard of care for affected children.

How Koselugo Is Taken

  • Form: Oral capsules
  • Typical dose: Based on body surface area (calculated from height and weight); usually taken twice daily, about 12 hours apart
  • Administration: Swallow capsules whole with water, on an empty stomach (no food 2 hours before or 1 hour after dosing)
  • Missed dose: Skip if more than 6 hours late; do not double up
  • Storage: Keep at room temperature, away from moisture and heat

Caregivers are trained to ensure proper dosing and to monitor for potential side effects.

Potential Benefits

Koselugo can provide several meaningful benefits for children with NF1 and plexiform neurofibromas:

  • Tumor shrinkage — often visible on MRI scans within months
  • Pain reduction and improved comfort
  • Better mobility and physical function
  • Improved appearance and reduced disfigurement from visible tumors
  • Enhanced quality of life for children and families

Response varies — not all tumors shrink, and ongoing treatment is often required to maintain benefits.

Possible Side Effects

Koselugo, like other targeted therapies, can cause side effects. The most common include:

  • Gastrointestinal symptoms: nausea, vomiting, diarrhea, abdominal pain
  • Skin problems: rash, dry skin, acne-like eruptions
  • Fatigue
  • Mouth sores
  • Swelling (especially around the eyes)
  • Changes in hair or nails

More serious but less common side effects include:

  • Heart problems (reduced ejection fraction) — periodic heart monitoring is required
  • Eye toxicity (retinal vein occlusion or detachment) — regular eye exams are needed
  • Liver enzyme elevation — blood tests are done regularly to monitor this
  • Increased creatine phosphokinase (CPK) — may indicate muscle irritation

Parents and caregivers should report any new or worsening symptoms to the healthcare provider promptly. Most side effects can be managed by adjusting the dose or providing supportive care.

Who Might Benefit Most

Koselugo is intended for:

  • Children 2 years and older
  • Diagnosed with neurofibromatosis type 1
  • Have symptomatic, inoperable plexiform neurofibromas causing pain, disfigurement, or organ compression

It is not approved for other types of NF1-related tumors or for NF2 (a separate condition). Treatment decisions should always be made by a multidisciplinary team familiar with NF1.

Practical Tips for Families

  • Follow dosing instructions exactly — consistent timing helps maintain effectiveness
  • Keep a side effect diary — note any skin changes, fatigue, or stomach upset
  • Encourage hydration and good nutrition
  • Plan regular follow-ups with the care team for scans and blood work
  • Seek support from NF1 advocacy organizations for educational and emotional resources

The Bottom Line

Koselugo (selumetinib) is the first targeted therapy approved for children with NF1-related plexiform neurofibromas. By addressing the molecular cause of tumor growth, it can help shrink tumors, reduce pain, and improve quality of life — offering new hope to patients and families facing this lifelong condition.

While ongoing monitoring and side effect management are essential, Koselugo has transformed the treatment landscape for NF1, opening the door for more research and future therapies.