Mirdametinib Scores FDA Priority Review in Neurofibromatosis Type 1 With PN

• The FDA has granted priority review to the new drug application of mirdametinib (formerly PD-0325901) in adult and pediatric patients with neurofibromatosis type 1-associated plexiform neurofibromas (NF1-PN).
• Mirdametinib is an investigational MEK inhibitor.
• A Prescription Drug User Fee Act (PDUFA) target action date of February 28, 2025, has been set.

Mirdametinib, an investigational MEK inhibitor, has been granted priority review by the FDA for the treatment of adult and pediatric patients with NF1-PN, and a PDUFA target action date of February 28, 2025, has been set.¹

The FDA grants priority review to applications of agents that, if approved, would offer significant improvements over currently available therapies or provide a treatment option for conditions where no adequate therapy currently exists.

The priority review is supported by data from the phase 2 ReNeu trial (NCT03962543), which were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

“This is the first study that really has provided good data regarding adults with NF1. And currently, there are no approved therapies for adults with NF1. Likewise, having an alternative that may have improved and improved toxicity profile is very important to this patient population,” said Christopher Moertel, MD, professor of pediatrics at the University of Minnesota and first author of the ReNeu study, in an interview with Targeted Oncology^TM.

Mirdametinib was previously granted orphan drug designation in this indication and fast track designation and rare pediatric drug designation for patients aged 2 and older.

About the Phase 2 ReNeu Study

In the phase 2 ReNeu study, 58 adult and 56 pediatric patients with NF1-PN were treated with the oral agent mirdametinib at a dose of 2 mg/m2 twice daily for 3 weeks on and 1 week off.² At the time of the data cutoff of September 22, 2023, the median treatment duration was 22 months, and the median duration of response was not reached.

The overall response rate was 41% (95% CI, 29%-55%; P <.001 vs null) in adult patients and 52% (95% CI, 38%-65%, P <.001 vs null) in pediatric patients. Additionally, 2 adult patients and 1 pediatric patient had a confirmed response in the long-term follow-up. The median target PN volumetric best response from baseline was –41% (range, –90% to 13%) in adult patients and –42% (range, –91% to 48%) in pediatric patients.

Regarding safety, the most common treatment-emergent adverse events (TEAEs) occurring in 35% or more of patients were dermatitis acneiform, diarrhea, nausea, and vomiting in adults and diarrhea, dermatitis acneiform, and vomiting in pediatric patients. Grade 3 or higher TEAEs occurred in 16% and 25% of adult and pediatric patients, respectively, while 22% and 9%, respectively, discontinued treatment due to TEAEs.

“These significant milestones bring us closer to our goal of delivering a transformative medicine to both adults and children with NF1-PN in the US and Europe,” said Saqib Islam, chief executive officer of SpringWorks, in a press release.¹ “People living with NF1-PN are in need of new advances and we look forward to working with the FDA and [European Medicines Agency] during their review processes as we prepare to bring our second medicine to patients suffering from devastating diseases.”

REFERENCES:

1. FDA grants priority review to SpringWorks Therapeutics’ new drug application for mirdametinib for the treatment of adults and children with NF1-PN. News release. SpringWorks Therapeutics, Inc. August 28, 2024. Accessed August 28, 2024. https://tinyurl.com/3bd2r8h8

2. Moertel, CL, Hirbe AC, Shuhaiber HH, et al. ReNeu: A pivotal phase 2b trial of mirdametinib in children and adults with neurofibromatosis type 1 (NF1)-associated symptomatic inoperable plexiform neurofibroma (PN). J Clin Oncol. 2024;42(suppl 16):abstr 3016. doi:10.1200/JC).2024.42.16_suppl.3016