REG - AstraZeneca PLC - Wainzua recommended for approval in the EU

AstraZenecaAnnouncement

21/10/2024 07:00

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RNS Number : 8568I  AstraZeneca PLC  21 October 2024

21 October 2024

 

Wainzua (eplontersen) recommended for approval in the EU by CHMP for the
treatment of adult patients with polyneuropathy associated with hereditary
transthyretin-mediated amyloidosis

 

Recommendation based on NEURO-TTRansform Phase III results showing Wainzua
demonstrated consistent and sustained benefit improving neuropathy impairment
and quality of life versus placebo

 

AstraZeneca and Ionis' Wainzua (eplontersen) has been recommended for approval
by the Committee for Medicinal Products for Human Use (CHMP) in the European
Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis
in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to
as hATTR-PN or ATTRv-PN.(1) If approved by the European Commission, Wainzua
will be the only approved medicine in the EU for the treatment of ATTRv-PN
that can be self-administered monthly via an auto-injector.(2-7)

 

The CHMP based its opinion on the positive NEURO-TTRansform Phase III trial
which showed that through 66 weeks, patients treated with Wainzua 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) versus external placebo.(2,8) Wainzua continued to
demonstrate a favourable safety and tolerability profile throughout the
NEURO-TTRansform trial.(2,8)

 

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.(9,10)

 

Dr Laura Obici, Head of Rare Diseases Unit, Consultant at the Amyloidosis
Research and Treatment Centre Istituto Di Ricovero e Cura a Carattere
Scientifico Fondazione Policlinico San Matteo, Pavia, Italy, said: "This
debilitating disease is ultimately fatal if left untreated and can have a
significant impact on many aspects of patients' and caregivers' day-to-day
lives. Having additional amyloidosis treatment options designed to reduce the
production of TTR protein at its source would potentially give patients more
time and ability to do what matters most to them and offer the hope of living
longer with a higher quality of life."

 

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit,
AstraZeneca, said: "Due to the progressive nature of polyneuropathy of
hereditary transthyretin-mediated amyloidosis, it is critical to have timely
diagnosis and new therapies to help people have greater control over this
potentially fatal disease. Today's recommendation brings Wainzua one step
closer for patients in Europe, and if approved, will offer a new treatment
option that can provide consistent TTR suppression and results in improved
quality of life."

 

Wainzua is a once-monthly silencer that provides upstream suppression of TTR
production.(2,3,11) It is an RNA-targeted medicine designed to reduce
production of TTR protein at its source in the liver to potentially treat all
types of transthyretin-mediated amyloidosis (ATTR).(2,3,11)

 

Wainzua was approved under the brand name Wainua for the treatment of ATTRv-PN
in the US
(https://www.astrazeneca.com/media-centre/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-us-treatment-of-adults-with-polyneuropathy-hereditary-transthyretin-mediated-amyloidosis.html)
in December 2023 and is now gaining approvals in additional countries
worldwide.(11,12) As part of a global development and commercialisation
agreement
(https://www.astrazeneca.com/media-centre/press-releases/2021/astrazeneca-ionis-to-collaborate-on-eplontersen.html)
, AstraZeneca and Ionis are commercialising Wainua for the treatment of
ATTRv-PN in the US.(11,12) The companies are seeking regulatory approval in
the EU and other parts of the world, where AstraZeneca has exclusive rest of
world commercialisation and development rights. Eplontersen was granted
Orphan Drug Designation in the US and in the EU for the treatment of
ATTR.(11,12)

 

Eplontersen is currently being evaluated in the CARDIO-TTRansform Phase III
trial for treatment of transthyretin-mediated amyloid cardiomyopathy
(ATTR-CM), the largest of all ATTR-CM trials to date including over 1,400
participants.(11-14)

Notes

 

TTR Amyloidosis

ATTR is caused by the accumulation of liver-derived misfolded TTR protein in
tissues, such as the heart and the peripheral nerves, causing organ damage and
failure.(2,15) ATTR then causes complications, leading to cardiovascular,
neurological and renal diseases such as heart failure (HF) and chronic kidney
disease.(15,16) There are both hereditary (ATTRv) and non-hereditary
(wild-type) forms of ATTR.(15) ATTR is a rapidly progressive and fatal disease
that requires timely recognition of symptoms.(15,17) ATTR has several
phenotypes including ATTR-CM, which predominantly impacts the heart,
potentially leading to HF, ATTRv-PN, which predominantly affects the
peripheral nervous system, and mixed phenotype, where patients experience
symptoms of both.(15,18) Worldwide, there are an estimated 300,000 - 500,000
patients with ATTR-CM and about 10,000 - 40,000 patients with ATTRv-PN.(11,18)

 

NEURO-TTRansform

NEURO-TTRansform is a global, open-label, randomised trial evaluating the
efficacy and safety of eplontersen in patients with ATTRv-PN.(2,19) The trial
enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 compared to the
external placebo.(2,19) The comparison of efficacy and safety
for eplontersen versus external placebo was based on data up to week
66.(2,19) All patients were then followed on treatment until week 85 and
evaluated four weeks after the last dose in an end-of-trial assessment.(2,19)
Following treatment and the end-of-trial assessments, patients were eligible
to enter an open-label extension study, which is still ongoing.(2) Full
results from the NEURO-TTRansform trial were published in The Journal of the
American Medical Association (JAMA)
(https://jamanetwork.com/journals/jama/fullarticle/2810248) further
demonstrating the benefit of Wainzua across the spectrum of ATTRv-PN at 35, 66
and 85 weeks of treatment.(2,19)

 

Wainzua

Wainzua is a once-monthly silencer that provides upstream suppression of TTR
production.(2,3,11) It is an RNA-targeted medicine designed to reduce
production of TTR protein at its source in the liver to potentially treat all
types of ATTR.(2,3,11)

 

AstraZeneca in CVRM
(https://www.astrazeneca.com/our-therapy-areas/cardiovascular-renal-and-metabolism.html)
 

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's innovative medicines are
sold in more than 125 countries and used by millions of patients worldwide.
Please visit astrazeneca.com (https://www.astrazeneca.com/) and follow the
Company on social media @AstraZeneca
(https://www.linkedin.com/company/astrazeneca/) .

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.

 

References

1.   European Medicines Agency  Internet . Meeting highlights from the
Committee for Medicinal Products for Human Use (CHMP) 14-17 October 2024
[cited 2024 October 18]. Available from:
https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-14-17-october-2024
(https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-14-17-october-2024)
.

2.   Coelho T, et al. Eplontersen for hereditary transthyretin amyloidosis
with polyneuropathy. JAMA. 2023;330(15):1448-1458.

3.   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(1):267-287.

4.   European Medicines Agency  Internet . Vyndaqel (Tafamidis). Summary of
product characteristics [cited 2024 October 8]. Available from:
https://ec.europa.eu/health/documents/community-register/2020/20200217147074/anx_147074_en.pdf
(https://ec.europa.eu/health/documents/community-register/2020/20200217147074/anx_147074_en.pdf)

5.   European Medicines Agency  Internet . Tegesdi (Inotersen). Summary of
product characteristics [cited 2024 October 8]. Available from:
https://www.ema.europa.eu/en/documents/product-information/tegsedi-epar-product-information_en.pdf
(https://www.ema.europa.eu/en/documents/product-information/tegsedi-epar-product-information_en.pdf)
.

6.   European Medicines Agency  Internet . Onpattro (Patisiran). Summary of
product characteristics [cited 2024 October 8]. Available from:
https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf
(https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf)
.

7.   European Medicines Agency  Internet . Amvuttra (Vutrisiran). Summary of
product characteristics [cited 2024 October 8]. Available from:
https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-product-information_en.pdf
(https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-product-information_en.pdf)
.

8.   AstraZeneca  Internet . Press release. NEURO-TTRansform Phase III
results presented at AAN showed eplontersen demonstrated consistent and
sustained improvement in all measures of disease and quality of life through
66 weeks [cited 2024 October 8]. Available from:
https://www.astrazeneca.com/media-centre/press-releases/2023/neuro-ttransform-phase-iii-results-presented-at-aan-showed-eplontersen-demonstrated-consistent-and-sustained-improvement.html
(https://www.astrazeneca.com/media-centre/press-releases/2023/neuro-ttransform-phase-iii-results-presented-at-aan-showed-eplontersen-demonstrated-consistent-and-sustained-improvement.html)
.

9.   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. 

10.  Nativi-Nicolau JN, et al. Screening for ATTR amyloidosis in the clinic:
overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail Rev.
2022;27(3):785-793.

11.  Ionis Pharmaceuticals  Internet . 2023 Annual Report [cited 2024
September 13]. Available from:
https://ir.ionis.com/static-files/aad58173-0ab5-4142-b6d4-3e940c7eb2a6
(https://ir.ionis.com/static-files/aad58173-0ab5-4142-b6d4-3e940c7eb2a6) .

12.  AstraZeneca  Internet . Press release. Wainua (eplontersen) granted
first-ever regulatory approval in the US for the treatment of adults with
polyneuropathy of hereditary transthyretin-mediated amyloidosis [cited 2024
October 8]. Available from:
https://www.astrazeneca.com/media-centre/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-us-treatment-of-adults-with-polyneuropathy-hereditary-transthyretin-mediated-amyloidosis.html
(https://www.astrazeneca.com/media-centre/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-us-treatment-of-adults-with-polyneuropathy-hereditary-transthyretin-mediated-amyloidosis.html)
.

13.  ClinicalTrials.gov  Internet . CARDIO-TTRansform: a study to evaluate
the efficacy and safety of eplontersen (formerly known as ION-682884,
IONIS-TTR-LRx and AKCEA-TTR-LRx) in participants with transthyretin-mediated
amyloid cardiomyopathy (ATTR CM) [cited 2024 October 8]. Available from
https://www.clinicaltrials.gov/study/NCT04136171
(https://www.clinicaltrials.gov/study/NCT04136171) .

14.  Ionis  Internet . Ionis completes enrollment in landmark Phase 3
CARDIO-TTRansform study in patients with TTR-mediated amyloid cardiomyopathy.
2023 July 31 [cited 2024 October 8]. Available from
https://ir.ionis.com/news-releases/news-release-details/ionis-completes-enrollment-landmark-phase-3-cardio-ttransform#:~:text=CARDIO%2DTTRansform%20is%20the%20largest,threatening%20cardiovascular%20(CV)%20events.

15.  Benson MD, et al. Diagnosis and screening of patients with hereditary
transthyretin amyloidosis (hATTR): Current strategies and guidelines. Ther
Clin Risk Manag. 2020;16:749-758.

16.  Adams D, et al. Expert consensus recommendations to improve diagnosis of
ATTR amyloidosis with polyneuropathy. J Neurol. 2021; 268(6): 2109-2122.

17.  Ando Y, et al. Guideline of transthyretin-related hereditary amyloidosis
for clinicians. Orphanet J Rare Dis. 2013;8:31.

18.  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(1):70.

19.  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. Neurol Ther. 2021;10(1):375-389.

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

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