REG - AstraZeneca PLC - Koselugo approved in Japan for NF1

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27/09/2022 07:16

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RNS Number : 8019A  AstraZeneca PLC  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 community."

 

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
(https://www.nejm.org/doi/full/10.1056/nejmoa1912735) 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.

 

Notes

NF1

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
years.(5,8-10)

 

SPRINT
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 Program (NTAP).

 

Koselugo

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

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

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 (http://www.astrazeneca.com/) and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

References

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
(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
(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. doi:
10.1016/S1474-4422(14)70063-8.

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
(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
(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?" Available at:
www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/neurofibromatosis-fact-sheet
(http://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/neurofibromatosis-fact-sheet)
. 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.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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