FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of September 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
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United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Koselugo recommended for EU approval
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.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 and
follow the Company on social media @AstraZeneca.
Contacts
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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.
Accessed September 2025.
Matthew Bowden
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
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AstraZeneca
PLC
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Date: 22 September 2025
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By: /s/
Matthew Bowden
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Name:
Matthew Bowden
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Title:
Company Secretary
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