Mirdametinib improves neurofibromatosis type 1-associated plexiform neurofibromas

Key takeaways:

• Mirdametinib is an investigational mitogen-activated protein kinase inhibitor.
• 52% and 41% of children and adults, respectively, achieved a 20% or greater reduction in tumor volume.

Positive results from a pivotal phase 2b trial showed mirdametinib significantly improved the outcomes of patients with neurofibromatosis type 1-associated plexiform neurofibromas, SpringWorks Therapeutics announced in a press release.

Neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN) are manifestations of a rare genetic disorder characterized as irregular, thick and noncircumscribed tumors of peripheral nerve sheath.

Mirdametinib, an investigational mitogen-activated protein kinase kinase inhibitor, has received orphan drug designation from the FDA and the European Commission for the treatment of NF1. Mirdametinib has also received the FDA’s fast track designation for the treatment of children aged 2 years and older with NF1-PN that have severely progressed and are experiencing morbidity.

“Plexiform neurofibromas can grow aggressively along peripheral nerves and lead to extreme pain, disfigurement and other morbidities that have a significant impact on the lives of patients and their families,” Saqib Islam, JD, CEO of SpringWorks, said in the release. “We are extremely pleased that the results of our ReNeu trial demonstrate a compelling clinical profile across measures of both safety and efficacy.”

ReNeu, an ongoing, multi-center, open-label, phase 2b trial, included 114 patients aged 2 years and older in the U.S. with inoperable NF1-PN. Each patient received mirdametinib at a dose of 2mg/m² twice daily without regard to food.

Within the 24-cycle treatment period with each cycle length spanning 28 days, 52% of pediatric patients and 41% of adult patients achieved a blinded independent central review confirmed objective response of a 20% or greater reduction in target tumor volume.

Additionally, another child and two adults achieved responses following cycle 24 in the long-term follow up phase of the trial which included continued mirdametinib treatment.

The pediatric cohort saw a –42% median change from baseline, whereas the adult cohort experienced a –41% change. All patients also reported statistically significant improvements in pain, quality of life and physical function.

Most adverse events were grade 1 or grade 2 making mirdametinib “generally well tolerated” by patients. However, 25% and 16% of pediatric and adult patients, respectively, experienced a grade 3 or higher treatment-related adverse event.

SpringWorks Therapeutics is planning to submit a new drug application to the FDA for mirdametinib in the first half of 2024, according to the press release.

“Our data indicates that mirdametinib has the potential to be the best-in-class therapy for children and the first approved treatment for adults with NF1-PN and we are working with urgency to bring this differentiated medicine to patients,” Islam said.

On Nov. 17, the percentage in the ninth paragraph was corrected to 16%. The editors regret the error.