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 2024
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.
KOMET Phase III trial met primary endpoint
12 November 2024
Koselugo showed
statistically significant and clinically meaningful objective
response rate vs. placebo in adults with neurofibromatosis type 1
in global KOMET Phase III trial
Results demonstrated reduction in tumour volume, building on
established safety and efficacy profile of Koselugo in children and
supporting expanded use in adults
Positive high-level results of KOMET, the largest, global
randomised double-blind placebo-controlled multicentre Phase III
trial in adults with neurofibromatosis type 1 (NF1) who have
symptomatic, inoperable plexiform neurofibromas (PN), showed
that Koselugo (selumetinib), an oral, selective MEK
inhibitor, met its primary endpoint, demonstrating a statistically
significant and clinically meaningful objective response rate (ORR)
versus placebo in these adult patients.
NF1 is a rare, progressive genetic condition affecting an estimated
1.7 million individuals worldwide, approximately 70% of whom are
adults.1,2 In
30-50% of patients, tumours develop on the nerve sheaths and may
cause debilitating symptoms.3-8 NF1
is usually diagnosed in early childhood, however, NF1 often
progresses into adulthood.9,10 There
are no approved treatments for adults, leaving many to experience
disfigurement, dysfunction, persistent pain or endure multiple
surgeries.11
Prof. Ignacio Blanco Guillermo, MD, PhD, Chairman of the Genetic
Counselling and Clinical Genetics Programme at the Germans Trias i
Pujol University Hospital, Chairman of the Spanish National
Reference Centre for Adult Patients with Neurofibromatosis and
Principal Investigator of the KOMET trial, said: "With limited
options to manage NF1 PN in adults, many patients experience
functional impairment and symptoms, which can substantially impact
their lives. These clinically meaningful data
show Koselugo has the potential to make a
positive impact in patient care by reducing the size of plexiform
neurofibromas."
Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare
Disease, said: "These promising results demonstrate
that Koselugo, the first and only approved targeted therapy for
certain children with NF1 PN, now has the potential to benefit
adult patients for whom there are no approved targeted therapies.
As the largest and only global placebo-controlled Phase III trial
in adults with NF1 PN, KOMET reinforces our leadership in advancing
potential treatment options for people living with this
debilitating disease. We look forward to sharing these findings
with regulatory authorities."
Scot Ebbinghaus, MD, Vice President, Global Clinical Development,
MSD Research Laboratories, said: "Adults with NF1 are in critical
need of treatment options to help manage symptomatic, inoperable
plexiform neurofibromas. These positive results from the Phase III
KOMET trial demonstrate the potential to expand the use
of Koselugo beyond paediatric patients to also treat
adult patients living with this rare and challenging genetic
condition."
In the trial, ORR was defined as the percentage of patients
with confirmed complete response (disappearance of PNs) or partial
response (at least 20% reduction in tumour volume) by cycle 16
(28 days per cycle) as determined by independent central
review (ICR) per response evaluation in neurofibromatosis and
schwannomatosis (REiNS) criteria.
The safety profile of Koselugo in this study was consistent with that
observed in clinical trials among children and adolescents. No new
safety signals were identified.
Alexion, AstraZeneca Rare Disease will share these data with
regulatory authorities and present at a
forthcoming medical meeting. AstraZeneca and MSD are
jointly developing and commercialising Koselugo globally.
Notes
NF1
NF1 is a rare, progressive, genetic condition that is caused by a
spontaneous or inherited mutation in the NF1
gene.3,11 NF1
is associated with a variety of symptoms, including soft lumps on
and under the skin (cutaneous neurofibromas) and, in 30-50% of
patients, tumours develop on the nerve sheaths
(PNs).4,11 These
PNs can cause clinical issues such as disfigurement, motor
dysfunction, pain, airway dysfunction, visual impairment and
bladder or bowel dysfunction.4-8 PNs
begin during early childhood, with varying degrees of severity, and
can reduce life expectancy by up to 15 years.5,8,11,12
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 PNs. 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 PNs, 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.13
The primary endpoint is confirmed 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).13
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.13
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 and has been granted
Orphan Drug Designation in the US, EU, Japan and other countries
for the treatment of certain paediatric patients with NF1 who have
symptomatic, inoperable PN.
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. Working together, the companies will
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
For details on how to contact the Investor Relations Team, please
click here. For
Media contacts, click here.
References
1. Evans DG, et al. Birth incidence
and prevalence of tumor-prone syndromes: estimates from a UK family
genetic register service. Am J Med Genet
A. 2010;152A(2):327-332.
2. Ejerskov C, et al. Clinical
characteristics and management of children and adults with
neurofibromatosis type 1 and plexiform neurofibromas in Denmark: a
nationwide study. Oncol Ther. 2023;11(1):97-110.
3. Tamura R. Current understanding of
neurofibromatosis type 1, 2, and
schwannomatosis. Int J Mol
Sci.
2021;22(11):5850.
4. Gross AM, et al.
Selumetinib in children with inoperable plexiform
neurofibromas. N Engl J
Med. 2020;382(15):1430-1442.
5. Hirbe AC, et al. Neurofibromatosis
type 1: a multidisciplinary approach to
care. Lancet
Neurol.
2014;13:834-843.
6. Dombi E, et al. Activity of
selumetinib in neurofibromatosis type 1-related plexiform
neurofibromas. N Engl J
Med. 2016;375:2550-2560.
7. Mayo Clinic.
Neurofibromatosis. Available here.
Accessed November 2024.
8. National Health
Service. Neurofibromatosis type 1, symptoms.
Available here.
Accessed November 2024.
9. Cancer.Net. Neurofibromatosis
type 1. Available here.
Accessed November 2024.
10. National Human Genome Research
Institute. About neurofibromatosis. Available here.
Accessed November 2024.
11. National Institute of
Neurological Disorders and Stroke. Neurofibromatosis.
Available here.
Accessed November 2024.
12. Evans DGR, et al. Reduced life
expectancy seen in hereditary diseases which predispose to
early-onset tumors. Appl Clin
Genet. 2013;6:53-61.
13. 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 2024.
Adrian Kemp
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:
12 November 2024
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By: /s/
Adrian Kemp
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Name:
Adrian Kemp
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Title:
Company Secretary
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