TIDMAZN
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 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(R) (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
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
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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
.
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
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