Selumetinib Granted Orphan Drug Designation in Japan for Neurofibromatosis Type 1

AstraZeneca announced selumetinib has been granted orphan drug designation (ODD) in Japan for the treatment of neurofibromatosis type 1 (NF1), a rare and debilitating genetic disease.

Selumetinib is co-developed and co-commercialized with Merck.

Some 30-50% of patients with NF1 experience plexiform neurofibromas (PN) - tumours growing along their nerve sheaths. These PN can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bowel/bladder dysfunction.

The Japanese Ministry of Health, Labour and Welfare grants ODD to medicines intended for the treatment of diseases that affect fewer than 50,000 patients in Japan and for which there is a high unmet medical need.

“Neurofibromatosis type 1 can have a devastating impact on children and new medicines are urgently needed to help treat the resulting plexiform neurofibromas and associated clinical issues. Current options in most countries are limited and this designation is a significant step forward in bringing the first medicine for NF1 to pediatric patients in Japan,” José Baselga, Executive Vice President, Oncology R&D, said.

“Plexiform neurofibromas are one of the key manifestations of NF1 and can lead to pain and disfigurement. In the SPRINT trial, selumetinib was shown to reduce the size of these tumors in children. We are hopeful that we will be able to bring this treatment to this underserved pediatric patient community in Japan,” Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said.

The National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored Phase I/II SPRINT Stratum 1 trial showed an overall response rate (ORR) of 66% (33 of 50 patients, confirmed partial response) in paediatric patients with NF1 PN when treated with selumetinib as a twice-daily oral monotherapy. ORR is defined as the percentage of patients with confirmed complete or partial response of at least 20% reduction in tumor volume.

AstraZeneca and MSD are jointly developing and commercializing selumetinib which was approved in the US in April 2020 under the medicine name Koselugo for the treatment of pediatric patients two years and older with NF1 and symptomatic, inoperable PN. A marketing authorization application in NF1 PN was accepted for review by the European Medicines Agency earlier in the year and further global regulatory submissions are underway.

NF1 is a debilitating genetic disease 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) and skin pigmentation (so-called ‘café 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 disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction. PN begin during early childhood, with varying degrees of severity, and can reduce life expectancy by 8 to 15 years.