Mirdametinib (MEK Inhibitor)
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GOMEKLI (mirdametinib) is an oral, small molecule MEK inhibitor that is approved in the U.S. for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
Mirdametinib is also in development for the treatment of pediatric low-grade glioma (LGG).
Mirdametinib (MEK inhibitor)
Mirdametinib inhibits MEK1 and MEK2, which occupy pivotal positions in the MAPK pathway. The MAPK pathway is a key signaling network that regulates cell growth and survival and that plays a central role in multiple cancers and rare diseases when dysregulated.
GOMEKLI (mirdametinib) for NF1-PN
GOMEKLI (mirdametinib) is approved in the U.S. for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection. The FDA approval of GOMEKLI is based on results from the single arm Phase 2b ReNeu trial, which enrolled 114 patients with NF1-PN ≥2 years of age (58 adults and 56 pediatric patients).
Data from the Phase 2b ReNeu trial were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology (Moertel CL, Hirbe AC, Shuhaiber HH, et al. ReNeu: a pivotal, Phase 2b trial of mirdametinib in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma. J Clin Oncol. 2024;[Epub ahead of print]:JCO.24.01034).
View full Prescribing Information for GOMEKLI.
Please see important safety information for GOMEKLI at the bottom of this page.
Mirdametinib in Pediatric Low-Grade Glioma
Pediatric LGG is a type of tumor that affects the brain and spinal cord. LGG is the most common central nervous system (CNS) tumor in children, accounting for approximately 30% of all childhood CNS tumors. LGG can arise in several different areas of the CNS including the cerebellum, cerebrum, brainstem, hypothalamus, visual pathway, optic nerve, and spinal cord. Low-grade gliomas are associated with significant morbidity including seizures and cognitive decline, and recurrent gliomas often undergo malignant transformation.
A Phase 2 study evaluating mirdametinib in pediatric and young adult patients with LGG is ongoing and enrolling patients.
Indication and Important Safety Information About GOMEKLI
GOMEKLI (mirdametinib) is indicated for the treatment of adult and pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic plexiform neurofibromas (PN) not amenable to complete resection.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Ocular Toxicity: GOMEKLI can cause ocular toxicity including retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), and blurred vision. In the adult pooled safety population, ocular toxicity occurred in 28% of patients treated with GOMEKLI: 21% were Grade 1, 5% were Grade 2 and 1.3% were Grade 3. RVO occurred in 2.7%, RPED occurred in 1.3%, and blurred vision occurred in 9% of adult patients. In the pediatric pooled safety population, ocular toxicity occurred in 19% of patients: 17% were Grade 1 and 1.7% were Grade 2. Conduct comprehensive ophthalmic assessments prior to initiating GOMEKLI, at regular intervals during treatment, and to evaluate any new or worsening visual changes such as blurred vision. Continue, withhold, reduce the dose, or permanently discontinue GOMEKLI as clinically indicated.
Left Ventricular Dysfunction: GOMEKLI can cause left ventricular dysfunction. GOMEKLI has not been studied in patients with a history of clinically significant cardiac disease or LVEF <55% prior to initiation of treatment. In the ReNeu study, decreased LVEF of 10 to <20% occurred in 16% of adult patients treated with GOMEKLI. Five patients (9%) required dose interruption, one patient (1.7%) required a dose reduction, and one patient required permanent discontinuation of GOMEKLI. The median time to first onset of decreased LVEF in adult patients was 70 days. Decreased LVEF of 10 to <20% occurred in 25%, and decreased LVEF of ≥20% occurred in 1.8% of pediatric patients treated with GOMEKLI. One patient (1.8%) required dose interruption of GOMEKLI. The median time to first onset of decreased LVEF in pediatric patients was 132 days. All patients with decreased LVEF were identified during routine echocardiography, and decreased LVEF resolved in 75% of patients. Before initiating GOMEKLI, assess ejection fraction (EF) by echocardiogram. Monitor EF every 3 months during the first year and then as clinically indicated. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.
Dermatologic Adverse Reactions: GOMEKLI can cause dermatologic adverse reactions including rash. The most frequent rashes included dermatitis acneiform, rash, eczema, maculo-papular rash and pustular rash. In the pooled adult safety population, rash occurred in 92% of patients treated with GOMEKLI (37% were Grade 2 and 8% were Grade 3) and resulted in permanent discontinuation in 11% of patients. In the pooled pediatric safety population, rash occurred in 72% of patients treated with GOMEKLI (22% were Grade 2 and 3.4% were Grade 3) and resulted in permanent discontinuation in 3.4% of patients. Initiate supportive care at first signs of dermatologic adverse reactions. Withhold, reduce the dose, or permanently discontinue GOMEKLI based on severity of adverse reaction.
Embryo-Fetal Toxicity: GOMEKLI can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to the initiation of GOMEKLI. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Also advise patients to use effective contraception during treatment with GOMEKLI and for 6 weeks after the last dose (females) or 3 months after the last dose (males).
ADVERSE REACTIONS
The most common adverse reactions (>25%) in adult patients were rash (90%), diarrhea (59%), nausea (52%), musculoskeletal pain (41%), vomiting (38%), and fatigue (29%). Serious adverse reactions occurred in 17% of adult patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormality (>2%) was increased creatine phosphokinase.
The most common adverse reactions (>25%) in pediatric patients were rash (73%), diarrhea (55%), musculoskeletal pain (41%), abdominal pain (39%), vomiting (39%), headache (34%), paronychia (32%), left ventricular dysfunction (27%), and nausea (27%). Serious adverse reactions occurred in 14% of pediatric patients who received GOMEKLI. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased neutrophil count and increased creatine phosphokinase.
USE IN SPECIFIC POPULATIONS
Verify the pregnancy status of patients of reproductive potential prior to initiating GOMEKLI. Due to the potential for adverse reactions in a breastfed child, advise patients not to breastfeed during treatment with GOMEKLI and for 1 week after the last dose.
To report SUSPECTED ADVERSE REACTIONS, contact SpringWorks Therapeutics Inc. at 1-888-400-7989 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Please see full Prescribing Information including Patient Information and Instructions for Use.