Mirdametinib

SpringWorks Therapeutics published Phase 2b ReNeu trial results for mirdametinib in the Journal of Clinical Oncology, showing significant confirmed objective response rates of 41% in adults and 52% in children with NF1-PN, deep and durable tumor volume reductions, and manageable safety profile. FDA PDUFA action date is February 28, 2025.

Oncology dominates pharmaceutical innovation, with 1,600 cancer drugs in development. Spending on cancer drugs is projected to reach $409 billion by 2028, with high costs for novel agents. Biosimilars and generics may provide savings but cannot match rising expenditures. The focus is shifting towards cell therapies for solid tumors, with 44% of trials initiated in 2023 targeting solid tumor indications. Several cancer drugs have been approved by the FDA this year, and many more are expected to receive approval decisions soon.

Various drugs and their statuses are listed, including IN-001 for anaphylaxis (Fast Track), Finereonone for heart failure (Phase 3), Tirzepatide for heart failure and obesity (Phase 3), TMB-001 for congenital ichthyosis (Phase 3), Bentracimab for ticagrelor reversal (Priority Review), Fabhalta for immunoglobulin A nephropathy (accelerated approval), RLS-0071 for acute graft-vs-host disease (Fast Track and Orphan Drug), CHIKV VLP for chikungunya (Priority Review), Diazoxide choline for Prader-Willi syndrome (Priority Review), Mirdametinib for neurofibromatosis type 1 (Priority Review), Setmelanotide for genetic obesity (Priority Review), AR882 for gout (Fast Track), SPN-830 for Parkinson disease (NDA review), BGB-16673 for chronic lymphocytic leukemia (Fast Track), Cabozantinib for neuroendocrine tumors (NDA review), Linvoseltamab for multiple myeloma (Complete Response Letter), Nivolumab plus ipilimumab for hepatocellular carcinoma (BLA review), Midomafetamine for PTSD (Complete Response Letter), and Tezepelumab-ekko for COPD (Breakthrough Therapy).

In August 2024, the FDA made several decisions on new therapeutic agents, including approving Indapta Therapeutics’ g-NK cell therapy IDP-023 for progressive multiple sclerosis, Amneal Pharmaceuticals’ carbidopa/levodopa ER capsules IPX203 for Parkinson disease, and Medtronic’s deep brain stimulation technology for use during general anesthesia. The agency also granted fast track designation to Abata Therapeutics’ Treg therapy ABA-101 for progressive MS and [18F]PI-2620 tau-PET diagnostic for neurodegenerative diseases. Additionally, the FDA cleared Clearmind Biomedical’s Neuroblade System for minimally invasive neurosurgery and granted priority review to SpringWorks Therapeutics’ mirdametinib for neurofibromatosis type 1-associated plexiform neurofibromas.

Mirdametinib, under development by SpringWorks Therapeutics, targets various cancers and tumors, with expected US revenue of $450 mn by 2034. The risk-adjusted NPV (rNPV) model, accounting for R&D risks, is used for valuation. SpringWorks reported FY2023 revenues of $5.5 mn and a net loss of $325.1 mn.

NeurologyLive's Friday 5 highlights: 1) Sharon Cohen on mivelsiran for early-stage Alzheimer disease; 2) Aliza Alter on BHV-7000 for focal epilepsy; 3) Jim Cassidy on mirdametinib for neurofibromatosis type 1; 4) Crystal Proud on SMA research and treatments; 5) Michael Levy on ravulizumab for NMOSD.

The FDA has granted priority review to SpringWorks Therapeutics' NDA for mirdametinib, an investigational MEK inhibitor for treating NF1-PN. The European Medicines Agency also validated the MAA for the same indication. Data from the ReNeu trial showed significant reductions in PN volume and improvements in pain and quality of life. SpringWorks anticipates potential launch in early 2025.

SpringWorks' CEO, Saqib Islam, expresses optimism about delivering a transformative medicine for NF1-PN in the U.S. and Europe, highlighting the need for new treatment advances. The FDA and EMA have granted various designations for mirdametinib, including Priority Review, Orphan Drug, Fast Track, and Rare Pediatric Disease, indicating its potential significance. The ReNeu trial results showed mirdametinib's efficacy in reducing tumor volume and improving quality of life with a manageable safety profile. Annette Bakker of the Children's Tumor Foundation congratulates SpringWorks on this milestone, emphasizing the urgent need for more treatment options for NF1 patients.

SpringWorks Therapeutics completes NDA submission to FDA for mirdametinib, an investigational MEK inhibitor for treating NF1-PN in children and adults. The submission includes data from the Phase 2b ReNeu trial, showing significant response rates, deep and durable responses, and a manageable safety profile. Mirdametinib has received Orphan Drug and Fast Track designations from the FDA and is planned for MAA submission to the EMA in the second half of 2024.