RNS Number : 8019A
27 September 2022
27 September 2022 07:05 BST
Koselugo approved in Japan for paediatric patients with
plexiform neurofibromas in neurofibromatosis type 1
First medicine approved in Japan to treat this rare and
debilitating genetic condition
Pivotal SPRINT trial showed Koselugo reduced tumour volume
Koselugo (selumetinib) has been approved in Japan for the
treatment of paediatric patients three years of age and older with
plexiform neurofibromas (PNs) in neurofibromatosis type 1 (NF1)
with clinical symptoms, such as pain and disfigurement, and PNs
which cannot be completely removed by surgery without risk of
substantial morbidity. (1)
The approval by the Japanese Ministry of Health, Labour and
Welfare (MHLW) is based on positive results from the SPRINT Stratum
1 Phase II trial sponsored by the National Institutes of Health's
National Cancer Institute (NCI) Cancer Therapy Evaluation Program
(CTEP). The trial showed Koselugo, an oral treatment option,
reduced the size of inoperable tumours in children.(1,2)
Additionally, a Phase I trial in Japanese paediatric NF1 patients
with symptomatic and inoperable PNs was also evaluated as a basis
for the approval, with the trial showing tumour reduction.
NF1 is a debilitating genetic condition affecting one in 3,000
individuals worldwide, most commonly diagnosed in children under
10.(3,4) In 30-50% of patients, tumours develop on the nerve
sheaths (plexiform neurofibromas) and can cause clinical issues
such as disfigurement, motor dysfunction, pain, airway dysfunction,
visual impairment and bladder or bowel dysfunction.(2,5-8)
Professor Yoshihiro Nishida, MD, PhD, Department of
Rehabilitation Medicine at Nagoya University, Nagoya, Japan, and
Japan Phase I trial investigator said: "People living with
plexiform neurofibromas caused by neurofibromatosis type 1 often
face painful physical, emotional and social burdens. This approval
marks a major step forward in addressing the debilitating impact
these plexiform neurofibromas have on paediatric patients living
with neurofibromatosis type 1 in Japan. Koselugo provides a
suitable intervention to treat symptomatic plexiform neurofibromas,
which may improve long-term patient activities of daily living and
quality of life."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "As the
first medicine approved in Japan for paediatric patients with
symptomatic, inoperable plexiform neurofibromas in
neurofibromatosis type 1, Koselugo offers new hope for patients and
families affected by this incurable genetic disease, whose only
previous treatment option was repeated surgery. This approval is a
testament to our longstanding commitment to rare disease research
and we are energised by the opportunity to further accelerate
innovation and care for the neurofibromatosis type 1
The SPRINT Stratum 1 Phase II trial showed Koselugo demonstrated
an objective response rate (ORR) of 66% (33 of 50 patients,
confirmed partial responses) in paediatric patients with PNs in NF1
when treated with Koselugo as twice-daily oral monotherapy.(1) ORR
is defined as the percentage of patients with confirmed complete
(disappearance of PNs) or partial response (at least 20% reduction
in tumour volume).(1) The most common adverse reactions in the
SPRINT trial were vomiting, blood creatine phosphokinase increase,
diarrhoea and nausea.(1)
Results from the SPRINT Stratum 1 Phase II trial were published
online in The New England Journal of Medicine .(2)
In addition to Japan, Koselugo is also approved in the US and EU
for the treatment of paediatric patients with NF1 and symptomatic,
inoperable PNs. Further regulatory submissions are underway.
NF1 is a debilitating genetic condition that is caused by a
spontaneous or inherited mutation in the NF1 gene.(9) NF1 is
associated with a variety of 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,
tumours develop on the nerve sheaths (plexiform
neurofibromas).(5,9) These plexiform neurofibromas (PNs) can cause
clinical issues such as disfigurement, motor dysfunction, pain,
airway dysfunction, visual impairment and bladder or bowel
dysfunction.(2,5-8) PNs begin during early childhood, with varying
degrees of severity, and can reduce life expectancy by up to 15
The SPRINT Stratum 1 Phase 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 Koselugo (selumetinib) monotherapy.(2)
This trial sponsored by NCI CTEP was conducted under a Cooperative
Research and Development Agreement between NCI and AstraZeneca with
additional support from Neurofibromatosis Therapeutic Acceleration
Koselugo (selumetinib) is the first and only approved therapy by
the Japanese MHLW for the treatment of paediatric patients three
years of age and older with plexiform neurofibromas (PNs) in
neurofibromatosis type 1 (NF1) with clinical symptoms, such as pain
and disfigurement, and PNs which cannot be completely removed by
surgery without risk of substantial morbidity.(1) Koselugo blocks
specific enzymes (MEK1 and MEK2), which are involved in stimulating
cells to grow.(1) In NF1, these enzymes are overactive, causing
tumour cells to grow in an unregulated way. By blocking these
enzymes, Koselugo slows down the growth of tumour cells.(1)
Koselugo is approved for use in the US, EU and Japan and has
received Orphan Drug Designation in Russia, Switzerland, South
Korea, Taiwan and Australia, and health authorities worldwide are
reviewing regulatory submissions.
AstraZeneca and MSD Strategic Collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Rahway, NJ,
US, known as MSD outside the US and Canada, announced a global
strategic collaboration to co-develop and co-commercialise Lynparza
and Koselugo (selumetinib), a mitogen-activated protein kinase
(MEK) inhibitor, for multiple cancer types. Working together, the
companies will develop Lynparza and Koselugo in combination with
other potential new medicines and as monotherapies. Independently,
the companies will develop Lynparza and Koselugo in combination
with their respective PD-L1 and PD-1 medicines.
Alexion, AstraZeneca Rare Disease, is the group within
AstraZeneca focused on rare diseases, created following the 2021
acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare
diseases for 30 years, Alexion is focused on serving patients and
families affected by rare diseases and devastating conditions
through the discovery, development and commercialisation of
life-changing medicines. Alexion focuses its research efforts on
novel molecules and targets in the complement cascade and its
development efforts on haematology, nephrology, neurology,
metabolic disorders, cardiology and ophthalmology. Headquartered in
Boston, Massachusetts, Alexion has offices around the globe and
serves patients in more than 50 countries.
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and follow the
Company on Twitter @AstraZeneca .
For details on how to contact the Investor Relations Team,
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1. Koselugo (selumetinib) Japanese prescribing information; 2022.
2. Gross AM, et al. Selumetinib in children with inoperable
plexiform neurofibromas. N Engl J Med. 2020 Apr
9;382(15):1430-1442. doi: 10.1056/NEJMoa1912735.
3. Cancer.Net. Neurofibromatosis Type 1. Available at: https://www.cancer.net/cancer-types/neurofibromatosis-type-1 . Accessed July 2022.
4. National Human Genome Research Institute. About Neurofibromatosis. Available at: https://www.genome.gov/Genetic-Disorders/Neurofibromatosis . Accessed July 2022.
5. Hirbe AC, Gutmann DH. Neurofibromatosis type 1: a
multidisciplinary approach to care. Lancet Neurol. 2014;13:834-43.
6. Dombi E, Baldwin A, Marcus LJ, et al. Activity of selumetinib
in neurofibromatosis type 1-related plexiform neurofibromas. N Engl
J Med. 2016;375:2550-2560. doi: 10.1056/NEJMoa1605943.
7. Mayo Clinic. Neurofibromatosis. Available at: https://www.mayoclinic.org/diseases-conditions/neurofibromatosis/symptoms-causes/syc-20350490 . Accessed July 2022.
8. NHS. Neurofibromatosis Type 1, Symptoms. Available at https://www.nhs.uk/conditions/neurofibromatosis-type-1/symptoms . Accessed July 2022.
9. National Institute of Neurological Disorders and Stroke.
Neurofibromatosis Fact Sheet. Available at: "What is NF1?"
. Last accessed: July 2022.
10. Evans DGR, Ingham SL. Reduced life expectancy seen in
hereditary diseases which predispose to early-onset tumors. Appl
Clin Genet. 2013;6:53-61.
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September 27, 2022 02:05 ET (06:05 GMT)
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