Xerocytosis, Hereditary

SpringWorks Therapeutics on Thursday released what it described as "positive" top-line results from a Phase IIb study of its experimental MEK inhibitor mirdametinib in patients with NF1-associated plexiform neurofibromas (NF1-PN). The company said it plans to submit a new drug application for mirdametinib to the FDA in the first half of 2024."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," commented CEO Saqib Islam.Mirdametinib, also known as PD-0325901, is designed to inhibit MEK1 and MEK2, crucial components in the MAPK pathway, a key signaling network that governs cell growth and survival, and that plays a central role in various oncology and rare disease conditions. The ReNeu trial enrolled 114 symptomatic, inoperable paediatric and adult patients with NF1-PNs, all of whom received oral mirdametinib twice-daily.Confirmed ORR of up to 52%As of the data cut-off of September 20, results showed that 52% of paediatric patients and 41% of adult patients had confirmed objective response rates (ORRs) within the 24-cycle treatment period, where cycle length was 28 days. SpringWorks noted that another paediatric patient and two additional adult patients achieved confirmed objective responses after cycle 24 in the long-term follow up phase of the trial.Further, the median best percent change from baseline in target tumour volume was calculated to be -42% and -41% in the paediatric and adult cohorts, respectively, while median duration of response was not reached in either group. Patients from both cohorts also "experienced statistically significant improvements from baseline in pain, quality of life, and physical function," according to the company.Meanwhile, 25% of paediatric patients and 16% of adult patients experienced a Grade 3 or higher treatment-related adverse event. Additional data are expected to be presented at an upcoming medical conference in the first half of 2024 and to be submitted for publication in a peer-reviewed journal.SpringWorks launched in 2017 with rights to a slate of four Pfizer drug candidates, which aside from mirdametinib also included nirogacestat for use in patients with desmoid tumours, senicapoc for hereditary xerocytosis and PF-0445784 to treat post-traumatic stress disorder. Analysts at H. C. Wainwright & Co. said they expect the FDA to approve nirogacestat in desmoid tumours by November 27.