AstraZeneca’s selumetinib granted orphan drug designation in Japan


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

Selumetinib is co-developed and co-commercialised with MSD Inc., Kenilworth, N.J., US (MSD: known as Merck & Co., Inc. inside the US and Canada).

Some 30-50% of patients with NF1 experience plexiform neurofibromas (PN) – tumours growing along their nerve sheaths.2 These PN can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment and bowel/bladder dysfunction.3

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.

José Baselga, Executive Vice President, Oncology R&D, said: “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 paediatric patients in Japan.”

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, 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 tumours in children. We are hopeful that we will be able to bring this treatment to this underserved paediatric patient community in Japan.”

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 tumour volume.

AstraZeneca and MSD are jointly developing and commercialising selumetinib which was approved in the US in April 2020 under the medicine name Koselugo for the treatment of paediatric patients two years and older with NF1 and symptomatic, inoperable PN. A marketing authorisation 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.1 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)1 and, in 30-50% of patients, tumours develop on the nerve sheaths (plexiform neurofibromas).2 These plexiform neurofibromas can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction.3 PN begin during early childhood, with varying degrees of severity, and can reduce life expectancy by 8 to 15 years.1,4,5


The SPRINT Stratum 1 Phase I/II trial was designed to evaluate the objective response rate and impact on patient-reported and functional outcomes in paediatric patients with NF1-related inoperable PNs treated with selumetinib monotherapy.6 Results were published in The New England Journal of Medicine.7 This trial sponsored by NCI CTEP was conducted under a Cooperative Research and Development Agreement between NCI and AstraZeneca with additional support from the Neurofibromatosis Therapeutic Acceleration Program (NTAP).


Selumetinib (available in the US under the medicine name Koselugo) is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2).6 MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers.

Selumetinib was granted US FDA Breakthrough Therapy Designation in April 2019, Rare Pediatric Disease Designation in December 2019, Orphan Drug Designation in February 2018, EU orphan designation in August 2018 and Swissmedic orphan drug status in December 2018 for the treatment of paediatric patients with NF1 PN.

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