REG - AstraZeneca PLC - Koselugo recommended for EU approval

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22/09/2025 07:05

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RNS Number : 2196A  AstraZeneca PLC  22 September 2025

22 September 2025

 

Koselugo recommended for approval in the EU by CHMP for plexiform
neurofibromas in adults with neurofibromatosis type 1

 

Recommendation based on KOMET Phase III trial results which showed 20%
objective response rate in tumour size reduction

 

Largest and only placebo-controlled, double-blind global Phase III trial in
adults builds on established profile in children to address unmet needs

 

Koselugo (selumetinib), an oral, selective MEK inhibitor, has been recommended
for approval in the European Union (EU) for the treatment of symptomatic,
inoperable plexiform neurofibromas (PN) in adult patients with
neurofibromatosis type 1 (NF1).

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) based its positive opinion on results from KOMET, the
largest and only placebo-controlled global Phase III trial in this patient
population, which were presented at the 2025 American Society of Clinical
Oncology (ASCO) Annual Meeting and published in The Lancet
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00986-9/fulltext)
.(1)

 

In the primary analysis of the trial, Koselugo showed a statistically
significant objective response rate (ORR) of 20% (n=14/71, 95% CI: 11.2, 30.9)
compared to 5% with placebo (n=4/74, 95% CI: 1.5, 13.3; p=0.01) by cycle
16.(1)

 

NF1 is a rare, progressive, genetic condition usually diagnosed in early
childhood, but often progressing into adulthood, that can impact every organ
system.(2,3) Up to 50% of people living with NF1 may develop a type of
non-malignant tumour called PN that may affect the brain, spinal cord and
nerves.(3,4) PN may appear later in a person's life and can grow and become
large, leading to pain, disfigurement and muscle weakness, among other
debilitating symptoms.(3,4)

( )

Prof. Pierre Wolkenstein, MD, PhD, Head of the Department of Dermatology at
Henri Mondor Hospital, APHP, Paris East University (UPEC), and National
Coordinating Investigator of the KOMET trial in Europe, said: "For adults with
NF1, tumour growth doesn't stop at childhood and can rapidly progress or
develop into adulthood, impacting physical, emotional and social well-being.
The positive recommendation by the CHMP for Koselugo in adults underscores the
urgent need for additional targeted treatments for this patient population.
When approved, Koselugo could offer a treatment option for adult patients and
continuity of care across age groups, supported by established clinical
experience and practice among doctors managing this lifelong condition."

 

Marc Dunoyer, Chief Executive Officer, Alexion, said: "The CHMP positive
opinion of Koselugo in adults with NF1 PN builds on more than a decade of
global clinical and real-world experience, reflecting the unmatched body of
evidence supporting the safety profile and efficacy of Koselugo. As
demonstrated by the results from KOMET, the largest and only
placebo-controlled, double-blind global Phase III trial in an adult
population, we continue to advance the pioneering legacy of Koselugo, which
set the treatment standard in NF1 PN, to reach even more people worldwide."

 

The safety profile of Koselugo in the KOMET Phase III trial was consistent
with its known profile and established use in paediatric patients.(1)

 

Koselugo has been recently approved in Japan and other countries for the
treatment of adult patients with NF1 who have symptomatic, inoperable PN based
on data from the KOMET Phase III trial, and additional regulatory reviews are
ongoing.

 

Notes

 

NF1
NF1 is a rare, progressive, genetic condition that is caused by a spontaneous
or inherited mutation in the NF1 gene.(2,3) NF1 is associated with a variety
of symptoms, including soft lumps on and under the skin (cutaneous
neurofibromas) and, in up to 50% of patients, tumours called plexiform
neurofibromas (PN) may develop on the nerve sheaths.(3,4) These PN can cause
clinical issues such as disfigurement, motor dysfunction, pain, airway
dysfunction, visual impairment and bladder or bowel dysfunction.(3,4)

 

KOMET

KOMET is a global Phase III randomised, double-blind, placebo-controlled,
multicentre trial designed to evaluate the efficacy and safety of Koselugo in
adults with NF1 who have symptomatic, inoperable PN. The trial enrolled 145
adults from 13 countries across North America, South America, Europe, Asia and
Australia, with participants' baseline characteristics, including gender and
distribution of PN, reflective of the global adult NF1 patient population.
Patients were enrolled and randomised to receive Koselugo or placebo (1:1) for
12 28-day cycles. Participants were required to have diagnosis of NF1, at
least one symptomatic, inoperable PN measurable by volumetric MRI analysis,
chronic PN pain score documented during screening, adequate organ and marrow
function and stable chronic PN pain medication use at enrolment.(1,5)

 

The primary endpoint is confirmed objective response rate (ORR) by cycle 16 as
assessed by ICR. ORR is defined as the percentage of patients with confirmed
complete response (disappearance of PNs) or partial response (at least 20%
reduction in tumour volume). Secondary endpoints include improved PN-related
pain and health-related quality of life (HRQoL) at cycle 12.(1,5)

 

After 12 cycles, patients on placebo were switched to Koselugo and patients on
Koselugo remained on treatment for an additional 12 cycles. Patients who had
the opportunity to complete 24 cycles of treatment have the option to
participate in a long-term extension period and continue to receive
Koselugo.(1,5)

 

Koselugo

Koselugo (selumetinib) is a kinase inhibitor that blocks specific enzymes
(MEK1 and MEK2), which are involved in stimulating cells to grow. In NF1,
these enzymes are overactive, causing tumour cells to grow in an unregulated
way creating so-called plexiform neurofibromas (PN). By blocking these
enzymes, Koselugo slows down the growth of tumour cells and, therefore,
the PN growth. 

 

Koselugo is approved in the US, EU, Japan, China and other countries for the
treatment of certain paediatric patients with NF1 who have symptomatic,
inoperable PN.

 

Koselugo is approved in Japan and other countries for the treatment of adult
patients with NF1 who have symptomatic, inoperable PN, and additional
regulatory reviews are ongoing

 

Koselugo has been granted Orphan Drug Designation in the US, EU, Japan and
other countries for the treatment of NF1.

 

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 (olaparib), a first-in-class PARP
inhibitor, and Koselugo. The companies may
develop Lynparza and Koselugo in combination with other potential new
medicines and as monotherapies.

 

Alexion

Alexion, AstraZeneca Rare Disease, is focused on serving patients and families
affected by rare diseases and devastating conditions through the discovery,
development and delivery of life-changing medicines. A pioneering leader in
rare disease for more than three decades, Alexion was the first to translate
the complex biology of the complement system into transformative medicines,
and today it continues to build a diversified pipeline across disease areas
with significant unmet need, using an array of innovative modalities. As part
of AstraZeneca, Alexion is continually expanding its global geographic
footprint to serve more rare disease patients around the world. It is
headquartered in Boston, US.

 

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's innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on social media @AstraZeneca
(https://gateway.zscalertwo.net/auD?origurl=https:%2f%2fwww.linkedin.com%2fcompany%2fastrazeneca&_ordtok=Mkk3WV5DBDPmQrD4F5MGdGDMZR)
.

 

Contacts 

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
. 

 

References

1.     Chen, AP, et al. KOMET: a phase 3, multicentre, international,
randomised, placebo-controlled study to assess the efficacy and safety of
selumetinib in adults with neurofibromatosis type 1 and symptomatic,
inoperable plexiform neurofibromas. The Lancet. 2025;405(10496):2217-2230.

2.   Tamura R. Current understanding of neurofibromatosis type 1, 2, and
schwannomatosis. Int J Mol Sci. 2021;22(11):5850.

3.   Hirbe AC, et al. Neurofibromatosis type 1: a multidisciplinary approach
to care. Lancet Neurol. 2014;13:834-843.

4.   Bergqvist C, et al. Neurofibromatosis 1 French national guidelines
based on an extensive literature review since 1966. Orphanet J Rare Dis.
2020;15(1):37.

5.   ClinicalTrials.gov. Efficacy and safety of selumetinib in adults with
NF1 who have symptomatic, inoperable plexiform neurofibromas (KOMET). NCT
Identifier: NCT04924608. Available here
(https://clinicaltrials.gov/study/NCT04924608) . Accessed September 2025.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

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