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 November 2025
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Koselugo (selumetinib) approved in the US
20 November
2025
Koselugo approved
in the US for adults with
neurofibromatosis type 1
Approval based on KOMET Phase III trial results which showed 20%
overall response rate in tumour size reduction
Alexion, AstraZeneca Rare Disease's Koselugo (selumetinib), an oral, selective MEK
inhibitor, has been approved in the US for the treatment of adult
patients with neurofibromatosis type 1 (NF1) who have symptomatic,
inoperable plexiform neurofibromas (PN).1
The approval by the US Food and Drug Administration (FDA) was based
on positive results from KOMET, the largest and only
placebo-controlled global Phase III trial in this patient
population. Data were presented at the 2025 American Society of
Clinical Oncology (ASCO) Annual Meeting and published
in The
Lancet.2
NF1 is a rare, progressive, genetic condition usually diagnosed in
early childhood, but often progressing into adulthood, that can
impact every organ system.3,4 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.4,5 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.4,5
Prof. Pierre Wolkenstein, MD, PhD, Head of the Department of
Dermatology at Henri Mondor Hospital, APHP, Paris East University
(UPEC), and Investigator of the KOMET trial, said: "The KOMET Phase
III trial, which builds on the established clinical profile
of Koselugo and its real-world use in paediatric
patients, underscores its potential to address the substantial and
oftentimes progressive clinical burdens associated with PN in
adulthood. This approval reaffirms the role
of Koselugo as a strong option for the treatment of
adult and paediatric patients with NF1 PN."
Marc Dunoyer, Chief Executive Officer, Alexion, said: "This
expanded approval of Koselugo in adults with NF1 PN, together with the
recently approved granule formulation for young children aged one
year and older, enables much-needed continuity of care and supports
patients across the disease journey in the US. As the first
approved therapy in NF1 PN, backed by more than a decade of
clinical evidence, Koselugo has transformed the treatment standard for
this rare disease."
Annette Bakker, PhD, Chief Executive Officer, Children's Tumor
Foundation, said: "We celebrate this FDA approval
of Koselugo for adults with NF1 plexiform
neurofibromas-a major step forward for NF patients
everywhere. Koselugo has already changed what is possible for
children with NF1, and now adults will benefit from that same
progress. It is proof that NF research is delivering real results
and opening the door to even more treatment options. This milestone
shows what can be achieved when scientists, clinicians, industry
and the NF community work together with one focus: getting
effective treatments to patients faster."
In the primary analysis of the KOMET Phase III
trial, Koselugo showed a statistically significant and
clinically meaningful overall response rate (ORR) of 20% (n=14/71,
95% confidence interval [CI]: 11, 31) compared to 5% with placebo
(n=4/74, 95% CI: 2, 13; p=0.011) by cycle 16, with 86% of patients
on Koselugo having an observed duration of response
(DOR) of at least 6 months. After 12 cycles, patients on placebo
were switched to Koselugo and patients on Koselugo remained on treatment for an additional 12
cycles.1
The safety of Koselugo in the KOMET Phase III trial was consistent
with its known profile and established use in paediatric
patients.2
Koselugo has
been recently approved in the EU, 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. In the
US, Koselugo granules have recently been approved for
paediatric patients one year of age and older with NF1
PN.
Notes
NF1
NF1 is a rare, progressive, genetic condition that is caused by a
spontaneous or inherited mutation in the NF1
gene.3,4 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.4,5 These
PN can cause clinical issues such as disfigurement, motor
dysfunction, pain, airway dysfunction, visual impairment and
bladder or bowel dysfunction.4,5
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.2,6
The primary endpoint is confirmed overall 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
12.2,6
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.2,6
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 the US, EU, 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.
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
For details on how to contact the Investor Relations Team, please
click here.
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References
1. Koselugo (selumetinib) US prescribing information;
November 2025.
2. 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.
3. Tamura
R. Current understanding of neurofibromatosis type 1, 2, and
schwannomatosis. Int J Mol
Sci. 2021;22(11):5850.
4. Hirbe
AC, et al. Neurofibromatosis type 1: a multidisciplinary approach
to care. Lancet
Neurol. 2014;13:834-843.
5. 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.
6. ClinicalTrials.gov.
Efficacy and safety of selumetinib in adults with NF1 who have
symptomatic, inoperable plexiform neurofibromas (KOMET). NCT
Identifier: NCT04924608. Available here.
Accessed November 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.
Date: 20 November 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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