On February 11, 2025, the U.S. Food and Drug Administration (FDA) approved SpringWorks Therapeutics’ drug, Gomekli (mirdametinib), for the treatment of neurofibromatosis type 1 (NF1) with symptomatic plexiform neurofibromas (PN). This approval applies to both adults and children aged two years and older who have tumors that cannot be surgically removed.
Understanding Neurofibromatosis Type 1 (NF1)
NF1 is a genetic disorder characterized by the development of tumors along nerves in the skin, brain, and other parts of the body. These tumors, known as neurofibromas, are typically noncancerous but can lead to various complications depending on their size and location. Plexiform neurofibromas (PN) are a subtype of these tumors that grow within nerve sheaths and can cause significant morbidity due to their potential for disfigurement, pain, and functional impairment. NF1 affects approximately 1 in 3,000 individuals worldwide, with an estimated 100,000 patients in the United States alone. Of these, 30% to 50% are likely to develop PN.
Challenges in Treating NF1-PN
The management of NF1-PN has historically been challenging. Surgical removal of these tumors is often not feasible due to their diffuse growth patterns and proximity to vital structures, making complete resection difficult without causing significant morbidity. Prior to Gomekli’s approval, treatment options were limited, and there was a significant unmet need for effective therapies that could reduce tumor burden and alleviate symptoms.
Gomekli: A New Therapeutic Option
Gomekli is an oral MEK inhibitor designed to target the MEK1 and MEK2 proteins, which play a role in the growth and survival of tumor cells. By inhibiting these proteins, Gomekli aims to reduce tumor size and associated symptoms. The FDA’s approval was based on data from a Phase 2b clinical trial, which demonstrated that Gomekli led to a reduction in tumor volume of 20% or more in 52% of pediatric patients and 41% of adult patients. These results underscore the drug’s potential to provide meaningful clinical benefits to patients with NF1-PN.
Administration and Availability
Gomekli is administered orally and is available in both capsule form and as a tablet that dissolves in water. This formulation is particularly beneficial for patients who have difficulty swallowing pills, such as young children or individuals with certain medical conditions. SpringWorks Therapeutics has announced that Gomekli will be available in the United States within two weeks of the approval date, providing timely access to this new treatment option.
Comparison with Existing Therapies
In 2020, the FDA approved AstraZeneca’s Koselugo (selumetinib) for the treatment of pediatric patients aged two years and older with NF1 and symptomatic, inoperable PN, making it the first drug specifically approved for this condition. Gomekli’s approval is noteworthy as it extends the treatment indication to include both adult and pediatric patients, thereby broadening the therapeutic options available to the NF1 community.
Corporate Developments
The approval of Gomekli marks SpringWorks Therapeutics’ second FDA-approved drug, following the approval of Ogsiveo for the treatment of desmoid tumors. This milestone further establishes the company’s presence in the field of rare diseases and oncology. Additionally, reports have emerged indicating that Germany’s Merck KGaA is in advanced discussions to acquire SpringWorks, signaling potential future developments in the company’s trajectory.
The FDA’s approval of Gomekli represents a significant advancement in the treatment landscape for NF1 patients with symptomatic PN. By providing a new therapeutic option that is effective across a broad age range, Gomekli addresses a critical unmet need and offers hope to patients and families affected by this challenging condition. As the medical community continues to explore and develop targeted therapies, the approval of Gomekli underscores the importance of innovative approaches in improving patient outcomes in rare genetic disorders.
