Gomekli Approved for NF1-Associated Plexiform Neurofibromas

The Food and Drug Administration (FDA) has approved Gomekli^™ (mirdametinib) for the treatment of adult and pediatric patients aged 2 years and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas not amenable to complete resection.

Plexiform neurofibromas (PN) are tumors that grow in an infiltrative pattern along the peripheral nerve sheath, resulting in pain and functional impairment in patients with NF1. Mirdametinib, an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2), has been shown in a mouse model to reduce neurofibroma tumor volume and proliferation by inhibiting downstream phosphorylation of extracellular signal-regulated kinase (ERK).

The approval was based on data from the open-label, phase 2b ReNeu trial (ClinicalTrials.gov Identifier: NCT03962543), which evaluated the safety and efficacy of mirdametinib in patients aged 2 years and older with an inoperable NF1-associated PN causing significant morbidity (N=114). Study participants received oral mirdametinib 2mg/m² twice daily for the first 21 days of each 28-day cycle until disease progression or unacceptable toxicity. 

The primary endpoint was confirmed overall response rate (ORR), defined as the proportion of patients with at least a 20% reduction in target tumor volume on consecutive scans during the 24-cycle treatment phase, as measured by magnetic resonance imaging and assessed by blinded independent central review. The study population included 58 adults (median age, 35 years) and 56 pediatric patients (median age, 10 years).

Findings showed treatment with mirdametinib resulted in statistically significant ORRs (41% in adults [95% CI, 29-55] and 52% in pediatric patients [95% CI, 38-65]; both P <.001). Median time to onset of response was 7.8 months (range: 4-19 months) for the adult cohort and 7.9 months (range: 4.1-18.8 months) for the pediatric cohort. 

In the adult group, responses of at least 12 months or 24 months duration were observed in 88% (n=21) and 50% (n=12) of patients with a confirmed response, respectively. Similarly, among pediatric patients with a confirmed response, 90% (n=26) had a response lasting at least 12 months and 48% (n=14) had a response lasting at least 24 months.  

Deep and durable reductions in PN volume were noted; median best percentage change in target PN volume was -41% in adults and -42% in children. Additionally, significant improvements in pain and health-related quality of life were observed. 

The safety profile was found to be manageable across both the adult and pediatric cohorts. The most common adverse reactions reported in adults were rash, diarrhea, nausea, musculoskeletal pain, vomiting, and fatigue; the most common grade 3 or 4 laboratory abnormality was increased creatine phosphokinase. In addition to these adverse reactions, pediatric patients also experienced abdominal pain, headache, paronychia, left ventricular dysfunction, and decreased neutrophil count (grade 3 or 4).

Gomekli is supplied as a capsule in 1mg and 2mg dosage strengths, as well as a 1mg tablet for oral suspension. The tablets for oral suspension can be swallowed whole or dispersed in water to create the oral suspension. 

As Gomekli can cause both ocular toxicity and left ventricular dysfunction, prior to initiating treatment, assessments of both vision and ejection fraction by echocardiogram should be conducted. The recommended dose of Gomekli is based on body surface area. Dosage modifications may be required to manage adverse reactions.

Gomekli is expected to be available within 2 weeks; patients will be able to access treatment through a specialty pharmacy.  

This article originally appeared on MPR