SpringWorks Therapeutics has initiated a Phase IIb clinical trial of its small molecule drug, mirdametinib, to treat adults and children suffering from neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas (NF1-PN).

NF1 is a rare genetic disease caused by NF1 gene mutations that affect the MAPK pathway, which is associated with various cancers and rare diseases.

Around 30% to 50% of NF1 patients go on to develop plexiform neurofibromas in their lifetime.

Plexiform neurofibromas are tumours of the peripheral nerve sheath that lead to significant pain, disfigurement and morbidity. NF1-PN currently lacks approved treatments.

Mirdametinib inhibits the MEK1 and MEK2 proteins associated with the MAPK pathway.

The open-label, multi-centre Phase IIb ReNeu trial will assess the safety, efficacy and tolerability of the drug in patients aged two years and above having an inoperable NF1-PN causing significant morbidity.

It will recruit around 100 patients in the US. The first patient in the trial has already been dosed.

Participants will be administered with a 2mg/m² to 4mg/m² twice-daily dose of mirdametinib, which will be calculated based on the body surface area. The drug will be administered in a three-week-on and one-week-off dosing schedule.

The trial’s primary endpoint is objective response rate, while secondary endpoints include safety, tolerability, duration of response, and changes in patient-reported outcomes from baseline.

SpringWorks Therapeutics CEO Saqib Islam said: “Unfortunately, up to half of all NF1 patients are at risk of developing plexiform neurofibromas, a more severe form of NF1 that causes painful tumours to grow on nerves throughout the body.

“While there are no therapies currently approved for these patients, several prior studies, including a Phase II study evaluating mirdametinib, have provided support for the mechanism of MEK inhibition in plexiform neurofibromas.”

Mirdametinib has orphan drug designation in the US and Europe for neurofibromatosis type 1, as well as fast track status in the US for NF1-PN that is progressing or associated with significant morbidity.