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 December 2023
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.
Wainua (eplontersen) granted first US FDA approval
22 December 2023
Wainua (eplontersen) granted first-ever regulatory
approval in the US for the treatment of adults with polyneuropathy
of hereditary transthyretin-mediated
amyloidosis
US FDA approval based on NEURO-TTRansform Phase III results showing
Wainua demonstrated consistent and sustained benefit improving
neuropathy impairment and quality of life
Additional regulatory reviews underway in rest of
world
AstraZeneca and Ionis' Wainua (eplontersen) has been approved in the
US for the treatment of the polyneuropathy of hereditary
transthyretin-mediated amyloidosis in adults, commonly referred to
as hATTR-PN or ATTRv-PN.1 Wainua is
the only approved medicine for the treatment of ATTRv-PN that can
be self-administered via an auto-injector.2-4
The approval by the US Food and Drug Administration
(FDA) was based on the positive 35-week interim
analysis from the NEURO-TTRansform Phase III trial, which
showed patients treated with Wainua demonstrated consistent and sustained
benefit on the co-primary endpoints of serum transthyretin (TTR)
concentration and neuropathy impairment measured by modified
Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint
of quality of life (QoL) on the Norfolk Quality of Life
Questionnaire-Diabetic Neuropathy (Norfolk
QoL-DN).2,5 Positive
results from the NEURO-TTRansform Phase III trial were published
in The
Journal of the American Medical Association
(JAMA) further
demonstrating the benefit of Wainua across the spectrum of ATTRv-PN at 35, 66
and 85 weeks.2
Michael J. Polydefkis, M.D., Professor of Neurology at Johns
Hopkins University School of Medicine and an investigator in the
NEURO-TTRansform study, said: "Many people living with
hereditary transthyretin-mediated amyloid polyneuropathy are unable
to fully enjoy their lives because of the relentless, progressive
and debilitating effects of the disease. Approval
of Wainua represents a meaningful advancement in
treatment, one that gives those who are living with
transthyretin-mediated amyloid
polyneuropathy help managing the
disease."
ATTRv-PN is a debilitating disease that leads to peripheral nerve
damage with motor disability within five years of diagnosis and,
without treatment, is generally fatal within a
decade.6 Wainua is
a ligand-conjugated antisense oligonucleotide (LICA) medicine
designed to reduce the production of TTR protein at its source to
treat both hereditary and non-hereditary forms of
transthyretin-mediated amyloidosis (ATTR).3,7,8
Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business
Unit, AstraZeneca, said: "There is an urgent medical need for
new therapies for people living with hereditary
transthyretin-mediated amyloid polyneuropathy. The US approval
of Wainua offers a new treatment option that
provides consistent and sustained reduction in serum TTR
concentration compared to baseline while halting disease
progression and improving quality of life for people living with
this debilitating condition."
Isabelle Lousada, President and CEO, Amyloidosis Research
Consortium, said: "People with hereditary
transthyretin-mediated amyloid polyneuropathy, and other forms of
amyloidosis, are often misdiagnosed since symptoms can mirror other
conditions. The path to getting an accurate diagnosis can often be
a long, arduous journey and it is critical that a timely and
accurate diagnosis is made not only for the individual experiencing
symptoms but for their families and loved ones. It is exciting to
see new innovations coming through and increased efforts to raise
awareness in an area that has often been overlooked or
neglected."
As part of a global development and commercialisation
agreement, AstraZeneca and Ionis will
commercialise Wainua for the treatment of ATTRv-PN in the US and
are seeking regulatory approval in Europe and other parts of the
world.8 This
agreement was recently expanded to include exclusive rights for
AstraZeneca to commercialise Wainua in Latin America in addition to all other
countries outside the US.9 Wainua was granted
Orphan Drug Designation in the US and in the EU for the
treatment of ATTR.9,10 Wainua will
be available in the US in January 2024.
Brett P. Monia, Ph.D., chief executive officer at Ionis, said: "The
FDA approval of Wainua marks an important milestone for people
living with hereditary transthyretin-mediated amyloid
polyneuropathy, who will now have an effective, well-tolerated
treatment that can be self-administered via
auto-injector to combat this devastating disease. It is also a
pivotal moment for Ionis as Wainua will be the first in a steady cadence of
potential commercial launches for the company. We are proud to have
discovered and, together with AstraZeneca,
developed Wainua, and are grateful to the patients, caregivers and
investigators who participated in our clinical studies, as well as
for the dedication of our scientists and
researchers."
Eplontersen is currently being
evaluated in the CARDIO-TTRansform Phase III
trial for treatment of
transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), a
systemic, progressive and fatal condition that typically leads
to progressive heart failure and often death within three-to-five
years from disease onset.11-13
Notes
TTR Amyloidosis
ATTR cardiomyopathy and polyneuropathy are progressive systemic
diseases caused by aging or genetic mutations (variants), resulting
in misfolded TTR protein and accumulation as amyloid fibrils in the
cardiac myocardium and peripheral nerves,
respectively.11,12 In
patients with ATTR, both hereditary and wild type (non-hereditary),
TTR protein builds up as fibrils in tissues, such as the peripheral
nerves and heart, gastrointestinal system, eyes, kidneys, central
nervous system, thyroid and bone marrow.3,11 The
presence of TTR fibrils interferes with the normal functions of
these tissues.12 As
the TTR protein fibrils accumulate, more tissue damage occurs and
the disease worsens, resulting in poor QoL and eventually
death.12 Worldwide,
there are an estimated 300,000 - 500,000 patients with ATTR-CM and
about 40,000 patients with ATTRv-PN.3,12
NEURO-TTRansform
NEURO-TTRansform is a global, open-label, randomised trial
evaluating the efficacy and safety of eplontersen in patients with
ATTRv-PN.2,5 The
trial enrolled adult patients with ATTRv-PN Stage 1 or Stage 2
compared to the external placebo group from the
TEGSEDI® (inotersen)
NEURO-TTR registrational trial that Ionis completed in
2017.2,5The
comparison of efficacy and safety for Wainua versus external placebo was based on data up
to week 66, and all patients were followed on treatment until week
85, when they had the option to transition into an open-label
extension study, which is still ongoing.2,5
Wainua
Wainua (eplontersen) is a
ligand-conjugated antisense oligonucleotide (LICA medicine designed
to reduce the production of transthyretin, or TTR
protein.2,7 Wainua has
been approved in the US for the treatment of the polyneuropathy of
hereditary transthyretin-mediated amyloidosis in adults (also
referred to as ATTRv-PN).1
AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of
BioPharmaceuticals, forms one of AstraZeneca's main disease areas
and is a key growth driver for the Company. By following the
science to understand more clearly the underlying links between the
heart, kidneys, liver and pancreas, AstraZeneca is investing in a
portfolio of medicines for organ protection by slowing or stopping
disease progression, and ultimately paving the way towards
regenerative therapies. The Company's ambition is to improve and
save the lives of millions of people, by better understanding the
interconnections between CVRM diseases and targeting the mechanisms
that drive them, so we can detect, diagnose and treat people
earlier and more effectively.
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 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. Wainua (eplontersen) US prescribing information;
2023.
2. Coelho T, et al. Eplontersen for Hereditary
Transthyretin Amyloidosis With
Polyneuropathy. JAMA. 2023;330(15):1448-1458.
3. Ionis Pharmaceuticals [Internet]. Annual Report,
2022 [last accessed 11 December 2023]. Available
from: https://ir.ionispharma.com/static-files/db9dff5d-8683-485a-a517-15e264fe7532.
4. Benson MD, et al. Diagnosis and
screening of patients with hereditary transthyretin amyloidosis
(hATTR): Current strategies and
guidelines. Ther
Clin Risk Manag.
2020;16:4749-758.
5. Coelho T, et al. Design and Rationale of the Global
Phase 3 NEURO-TTRansform Study of Antisense Oligonucleotide
AKCEA-TTR-LRx(ION-682884-CS3) in Hereditary Transthyretin-Mediated
Amyloid Polyneuropathy. Nerol Ther. 2021 Jun;10(1):375-389.
6. Cortese A, et al. Diagnostic challenges in
hereditary transthyretin amyloidosis with polyneuropathy: avoiding
misdiagnosis of a treatable hereditary
neuropathy. J Neurol Neurosurg
Psychiatry.
2017;88(5):457-458.
7. Coelho T, et al. Characteristics of Patients
with Hereditary Transthyretin Amyloidosis-Polyneuropathy (ATTRv-PN)
in NEURO-TTRansform, an Open-label Phase 3 Study of
Eplontersen. Neurol Ther. 2023;12:267-287.
8. Ionis Pharmaceuticals [Internet]. Eplontersen
continued to show improvement in ATTRv-PN through 85 weeks [last
accessed 11 December 2023]. Available
from: https://ir.ionispharma.com/news-releases/news-release-details/eplontersen-continued-show-improvement-attrv-pn-through-85-weeks.
9. Ionis Pharmaceuticals [Internet]. Ionis expands
eplontersen agreement with AstraZeneca to include exclusive rights
in Latin America [last accessed 11 December 2023]. Available
from: https://ir.ionispharma.com/news-releases/news-release-details/ionis-expands-eplontersen-agreement-astrazeneca-include.
10. European Commission. Commission Implementing
Decision of 13.10.2023 relating to the designation of "Eplontersen"
as an orphan medicinal product under Regulation (EC) No 141/2000 of
the European Parliament and of the Council [last accessed 11
December 2023]. Available from: https://ec.europa.eu/health/documents/community-register/2023/20231013160615/dec_160615_en.pdf.
11. Viney N, et al. Ligand conjugated antisense
oligonucleotide for the treatment of transthyretin amyloidosis:
preclinical and phase 1 data. ESC Heart
Failure. 2021;
8:652-661.
12. Rintell D, et al. Patient and family experience with
transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy
(ATTR-PN) amyloidosis: results of two focus
groups. Orphanet J Rare
Dis. 2021;16:70.
13. Columbia University Irving Medical Center
[Internet]. Drug Reduces Death from Underdiagnosed Form of Heart
Failure [last accessed 11 December 2023]. Available
from: https://www.cuimc.columbia.edu/news/drug-reduces-deaths-underdiagnosed-form-heart-failure.
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.
Date:
22 December 2023
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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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