REG - AstraZeneca PLC - Wainua (eplontersen) granted first US FDA approval

AstraZenecaAnnouncement

22/12/2023 07:00

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RNS Number : 7566X  AstraZeneca PLC  22 December 2023

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
(https://ir.ionispharma.com/news-releases/news-release-details/ionis-completes-enrollment-landmark-phase-3-cardio-ttransform)
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.(2,5)The 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 (https://www.astrazeneca.com/)

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 (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

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.

 

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
(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
(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
(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
(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
(https://www.cuimc.columbia.edu/news/drug-reduces-deaths-underdiagnosed-form-heart-failure)
.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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