AstraZeneca and Merck announced that the U.S. FDA has accepted a New Drug Application (NDA) and granted priority review for the MEK 1/2 inhibitor selumetinib for pediatric patients aged three years and older with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PNs). A Prescription Drug User Fee Act (PDUFA) date is set for the second quarter of 2020.
This NDA regulatory submission was based on positive results from the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored SPRINT Phase 2 Stratum 1 trial. An objective response rate (ORR) was achieved in 66% of pediatric patients with NF1 and symptomatic, inoperable PNs (n=33/50 patients) when treated with selumetinib as a twice-daily oral monotherapy. ORR was defined as the percentage of patients with a confirmed complete or partial response of ≥ 20% tumor volume reduction.
Selumetinib was granted U.S. FDA Breakthrough Therapy Designation for this population in April of 2019, U.S. FDA Orphan Drug Designation in February of 2018, EU Orphan Drug Designation by the European Medicines Agency in August 2018, and Swissmedic Orphan Drug Status in December 2018.
AstraZeneca and Merck have a global strategic collaboration agreement to co-develop and co-commercialize selumetinib.
Selumetinib is an investigational MEK 1/2 inhibitor. It is designed to inhibit the MEK enzyme in the RAS/MAPK pathway, a cell-signaling pathway, associated with cancer cell growth and proliferation in a number of different tumor types.
About Neurofibromatosis Type 1 (NF1)
NF1 is an incurable genetic condition that affects one in every 3,000 to 4,000 individuals. It is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas), skin pigmentation (so-called ‘cafe au lait’ spots) and, in 30-50% of patients, tumors develop on the nerve sheaths (plexiform neurofibromas). These plexiform neurofibromas can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bowel/bladder dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumors (MPNST).