Priority Review given to mirdametinib to treat NF1-PN in children, adults

Priority Review given to mirdametinib to treat NF1-PN in children, adults | Image Credit: © Araki Illustrations - © Araki Illustrations - stock.adobe.com.

The FDA has granted Priority Review Designation to SpringWorks Therapeutics and accepted its New Drug Application for mirdametinib to treat adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN).

The investigational MEK inhibitor has been assigned a Prescription Drug User Fee Act (PDUFA) date of February 28, 2025. The rare genetic disorder arises from loss-of-function variants in the NF1 gene, which encodes for neurofibromin, a key suppressor of the MAPK pathway. There is an estimated global birth incidence of approximately 1 in 2,500 individuals, and approximately 100,000 patients living with NF1 in the United States.

"NF1 patients have approximately a 30-50% lifetime risk of developing plexiform neurofibromas, or PN, which are tumors that grow in an infiltrative pattern along the peripheral nerve sheath and that can cause severe disfigurement, pain and functional impairment; in rare cases, NF1-PN may be fatal," stated Spring Works.

Submission to the FDA included data from the phase 2b ReNeu trial (NCT03962543) evaluating mirdametinib in patients aged 2 years or older with NF1-associated PN causing significant morbidity. Results, presented in an oral presentation at the 2024 American Society of Clinical Oncology Annual Meeting, demonstrated that mirdametinib objective response rates, improvement in pain and health-related quality of life, along with a "manageable safety profile across both the adult and pediatric cohorts," according to SpringWorks.

The trial enrolled 114 patients to receive mirdametinib at a dose of 2 mg / m2 twice daily without regard to food. It was administered orally in a 3-week on, 1-week off dosing schedule as either a capsule or dispersible tablet.

The primary endpoint was confirmed objective response rate assessed by proportion of patients with a 20% or greater reduction in target tumor volume on consecutive scans in a 24 cycle treatment phase, measured by MRI.

"People living with NF1-PN are in need of new advances and we look forward to working with the FDA and EMA during their review processes as we prepare to bring our second medicine to patients suffering from devastating diseases," said Saqib Islam, Chief Executive Officer of SpringWorks, in the press release.

“Plexiform neurofibromas may sit next to or surround vital organs and can cause serious medical complications for patients. While progress has been made, there remains a pressing need for more treatment options, particularly for adults who currently have no approved therapy,” said Annette Bakker, PhD, CEO, Children’s Tumor Foundation (CTF); Board Chair of CTF Europe. “CTF is dedicated to deploying its time, talent and funding towards accelerating the development of new treatments. We are thrilled that patients in the United States and Europe could soon have a new therapy available to them.”

Reference:

FDA Grants Priority Review to SpringWorks Therapeutics’ New Drug Application for Mirdametinib for the Treatment of Adults and Children with NF1-PN. SpringWorks Therapeutics Inc. Press release. August 28, 2024. Accessed August 29, 2024.