Additional clinical and real-world data from
the industry’s largest and broadest amyloidosis pipeline will
advance understanding of underlying mechanisms of disease and unmet
needs
AstraZeneca and Alexion, AstraZeneca Rare Disease, will showcase
14 studies, including real-world evidence (RWE), from their
portfolio and pipeline of investigational amyloidosis therapies at
the International Symposium on Amyloidosis (ISA), in Rochester, MN
from May 26–30, 2024.
AstraZeneca and Ionis will present new subgroup analyses of the
Phase 3 NEURO-TTRansform study of WAINUATM (eplontersen), which was
approved by the US Food and Drug Administration (FDA) in December
2023 for the treatment of the polyneuropathy of hereditary
transthyretin-mediated amyloidosis in adults, commonly referred to
as hATTR-PN or ATTRv-PN.1 Additionally, clinical data will be
presented on ALXN2220 and anselamimab, which are being evaluated in
Phase III clinical trials for ATTR and light chain (AL)
amyloidosis, respectively.
Sarah Walters, Vice President, US Cardiovascular, Renal &
Metabolic Diseases, AstraZeneca, said: “AstraZeneca is dedicated to
advancing the science and improving the lives of patients that are
impacted by this devastating disease. Our data at the 2024
International Symposium on Amyloidosis demonstrate the leadership
commitment AstraZeneca, Alexion and our partners Ionis and
Neurimmune have to develop best in class treatment options to serve
a broad range of amyloidosis patients.”
Christophe Hotermans, Senior Vice President, Head of Global
Medical Affairs, Alexion, said: “With the largest and
fastest-growing pipeline of investigational amyloidosis therapies,
we are working to advance multiple modalities with the potential to
halt, reduce or reverse organ damage. Key presentations at the ISA
Annual Meeting include live-cell imaging and Phase I clinical data
evaluating the ability of ALXN2220 to remove amyloid from cardiac
tissue, to support its further study as a potential treatment for
advanced ATTR cardiomyopathy. Additionally, findings on
epidemiology and patient renal outcomes will reinforce the urgency
for differentiated amyloidosis diagnosis and additional treatment
options in AL amyloidosis.”
Robust evidence program increases understanding of
amyloidosis patient characteristics and treatment
effectiveness.
In addition to sub-analyses of the NEURO-TTRansform data,
AstraZeneca will present US patient characteristics data,
preliminary data from the OverTTuRe study measuring prevalence and
characteristics of phenotypes in patients with ATTR amyloidosis in
the United States and Japan; as well as the MaesTTRo study design,
part of a global, multi-study, real-world evidence program designed
to fill the evidence gaps of the effectiveness of treatments for
ATTR.
WAINUA is currently being evaluated in the Phase 3
CARDIO-TTRansform study for adults with cardiomyopathy of
transthyretin-mediated amyloidosis (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.2-5 The CARDIO-TTRansform Phase 3 study is fully
enrolled with more than 1,400 patients–making it the largest study
in this patient population to date.6
As part of a global development and commercialization agreement,
AstraZeneca and Ionis are commercializing WAINUA for the treatment
of hATTR-PN in the US and are seeking regulatory approval in Europe
and other parts of the world.6
Novel investigational amyloid depleter assets demonstrate
potential to improve outcomes for amyloidosis patients
High-resolution live-cell imaging will offer new insight into
the underlying cellular mechanism of antibody-mediated amyloid
removal with ALXN2220. Results will show the addition of ALXN2220
to ATTR patient-derived cardiac tissue triggered phagocytosis,
including recruitment of macrophages to amyloid deposits,
detachment, internalization and degradation of ATTR amyloid.
An encore poster presentation will report results from the
first-in-human study of ALXN2220. Initial treatment with ALXN2220
was well tolerated with a transient increase in C-reactive
proteins, suggesting initial targeted immune activation and
recruitment of phagocytic immune cells. Additionally, an encore
poster presentation will describe the pharmacokinetic and
pharmacodynamic (PK/PD) model used for the selection of the dose
range, dose escalation, dosing interval and study duration.
Further, a poster will outline the baseline demographics and
characteristics of the 406 participants of the Alexion CARES
clinical program evaluating anselamimab in patients with Mayo Stage
IIIa and IIIb AL amyloidosis, which includes the largest
prospective AL amyloidosis study to date in advanced stage AL
amyloidosis.
Advancing understanding of the amyloidosis landscape
A retrospective chart analysis from the US EMR TriNetX database
will report outcomes in AL amyloidosis patients with renal
involvement receiving bortezomib or daratumumab. Only half of
patients were renal-responders and few achieved renal complete
response (renCR, proteinuria ≤200 mg/day), underscoring the unmet
medical need for this patient subset.
Retrospective analyses will also be presented across three
posters on the incidence and prevalence of AL and ATTR amyloidosis,
reinforcing the importance of timely diagnosis of amyloidosis and
continued monitoring.
A comprehensive list of AstraZeneca key abstracts to be
presented at the 2024 International Symposium on Amyloidosis
includes7:
Lead author
Abstract title
Presentation details
Poster presentation session 1:
10:00-10:30
Poster presentation session 2:
14:45-15:45
Eplontersen
Gillmore JD, Davis M, Hahn K, Smith G,
Shivappa N, Papas M, Folkvaljon F, Pao C, Sundin AK, L Wittbrodt E,
Grogan M
Prospective, Real-World Data on the
Characteristics, Treatment Patterns, and Outcomes of Patients With
Transthyretin Amyloidosis: Design of the MaesTTRo Study
Date: Wednesday, May 29 Abstract
ID: 204
Waddington Cruz M, Berk J, Parman Y, Gertz
M, Khella S, Weiler M, Kwoh J, Chen J, Reicher B, Nåtman J,
Dasgupta N
Eplontersen for Hereditary Transthyretin
Amyloidosis With Polyneuropathy: An Exploratory Analysis of
Treatment Effect in Male and Female Patients
Date: Wednesday, May 29 Abstract ID:
202
Gillmore JD, Adams D, Weiler M, Masri A,
Obici L, Kwoh J, Reicher B, Chen J, Waddington Cruz M, Natman J,
Gertz M
Eplontersen for Hereditary Transthyretin
Amyloidosis With Polyneuropathy: An Exploratory Analysis in
Patients With the V30M TTR variant and Early-onset or Late-onset
Disease
Date: Wednesday, May 29 Abstract ID:
230
Wixner J, Conceição I, Berk J, Adams D,
Polydefkis M, Attarian S, Gillmore J, Dyck J, Coelho T, Chen J,
Hardy E, Kwoh J, Nåtman J, Waddington Cruz M
Neuropathy Impairment and Nutritional
Status With Eplontersen in Patients With Hereditary
Transthyretin-Mediated Amyloidosis
Date: Wednesday, May 29 Abstract ID:
174
Alexander K, Alvarez C, Kumar N, Pao C,
Wittbrodt E, Kohsaka S
Prevalence and Descriptive Characteristics
of Clinical Phenotypes in Patients With ATTR amyloidosis in the
United States and Japan: Preliminary Results from the OverTTuRe
Study
Date: Monday, May 27 Abstract ID: 198
Bazell C, Alston M, Kumar N, Huang J,
Venditto J, Grillis D, Eisenberg S, Nativi-Nicolau J
Descriptive Characteristics of Patients
Diagnosed With Transthyretin Amyloidosis in the Commercial and
Medicare Populations
Date: Wednesday, May 29 Abstract ID:
518
ALXN 2220
Michalon A, Huy, Mercuri M, Kahr P, Hock
C, Grimm J
ALXN2220: High-resolution Live-cell
Imaging of Antibody-mediated Cardiac ATTR Amyloid Depletion
Date: Tuesday, May 28 Abstract ID: 226
Michalon A, Renaud L, Machacek M, Cortijo
C, Udaata C, Mercuri M, Buller F, Hock C, Nitsch R, Kahr P, Grimm
J
Prediction of Cardiac ATTR Depletion by
NI006 Using Mechanistic PK/PD Modeling
Date: Wednesday, May 29 Abstract ID:
291
Aus dem Siepen F, Van der Meer P, Damy T,
Garcia-Pavia P, Donal E, Lairez O, Blank A, Kristen A, Quarta CC,
Buchele G, Mercuri M, Hock C, Michalon A, Kahr P, Rey S, Tichy
M
ALXN2220: Targeted Immune Activation in
Patients Undergoing Antibody-mediated Cardiac ATTR Amyloid
Depletion
Date: Wednesday, May 29 Abstract ID:
227
Amyloidosis Incidence and
Analyses
Laires PA, Evans J, Thompson J, Manwani R,
Mudumby P, Field M, Fang S
Prevalence, Incidence, and
Characterization of Light Chain Amyloidosis in the USA: A
Real-World Analysis Utilizing Electronic Health Records (EHR)
Date: Monday, May 27 Abstract ID: 65
Manwani R, Yang F, Zhang Y, Laires PA
Outcomes in Patients With AL Amyloidosis
With Renal Involvement: Findings from the TriNetX Database
Date: Monday, May 27 Abstract ID: 113
Laires PA, Li SXL, Uday A, Kumar P, Silva
AM, Quarta C
Prevalence and Incidence of ATTR
Amyloidosis in the United States: Insights from Claims Database and
Electronic Health Records
Date: Tuesday, May 28 Abstract ID: 68
Laires PA, Zhang Y, Manwani R, Silva AM,
Catini J, Thompson J, Dozier M, Yang F
Subtype Distribution of Amyloidosis in the
United States: Insights from an Electronic Health Records Database
Analysis
Date: Tuesday, May 28 Abstract ID: 112
The full list of ISA 2024 congress abstracts are available
online.
INDICATION for WAINUATM (eplontersen)
WAINUA injection, for subcutaneous use, 45 mg is indicated for
the treatment of the polyneuropathy of hereditary
transthyretin-mediated amyloidosis in adults.
IMPORTANT SAFETY INFORMATION for WAINUATM
(eplontersen)
WARNINGS AND PRECAUTIONS
Reduced Serum Vitamin A Levels and Recommended
Supplementation WAINUA leads to a decrease in serum vitamin A
levels. Supplement with recommended daily allowance of vitamin A.
Refer patient to an ophthalmologist if ocular symptoms suggestive
of vitamin A deficiency occur.
ADVERSE REACTIONS
Most common adverse reactions (≥9% in WAINUA-treated patients)
were vitamin A decreased (15%) and vomiting (9%).
Please see link to US Full Prescribing Information for
WAINUA.
Notes
NEURO-TTRansform
NEURO-TTRansform is a global, open-label, randomized trial
evaluating the efficacy and safety of eplontersen in patients with
hATTR-PN.8,9 The trial enrolled adult patients with hATTR-PN Stage
1 or Stage 2 compared to the external placebo group from the
NEURO-TTR registrational trial that Ionis completed in 2017.8,9 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.8,9
WAINUA
WAINUATM (eplontersen) is a ligand-conjugated antisense
oligonucleotide (LICA) medicine designed to reduce the production
of transthyretin, or TTR protein.9,10 WAINUA has been approved in
the US for the treatment of the polyneuropathy of hereditary
transthyretin-mediated amyloidosis in adults (also referred to as
hATTR-PN).1
AstraZeneca in amyloidosis
Amyloidosis is a group of complex rare diseases caused by
abnormal proteins that misfold and clump together to form toxic
amyloids that deposit in tissues or organs, including the heart,
kidneys and peripheral nerves.11,12 The build-up of these toxic
amyloids can result in significant organ damage and organ failure
that can severely impact quality of life and ultimately be
fatal.11,12 AstraZeneca and its Rare Disease Unit, Alexion, are
developing and evaluating multiple modalities with the potential to
halt and reduce organ damage across various types of amyloidosis.
The Company is uniquely positioned to lead therapeutic and
diagnostic advances for people living with amyloidosis with the
largest and fastest-growing pipeline of investigational amyloidosis
therapies to address the spectrum of patient needs.
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, MA, US.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialization 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. For more
information, please visit www.astrazeneca-us.com and follow us on
social media @AstraZeneca.
References
- WAINUATM (eplontersen) [prescribing information]. Wilmington,
DE: AstraZeneca Pharmaceuticals LP; 2023.
- 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.
- 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.
- 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.
- ClinicalTrials.gov. 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) [last
accessed 21 May 2024] Available from:
https://classic.clinicaltrials.gov/ct2/show/NCT04136171.
- Ionis Pharmaceuticals [Internet]. WAINUA™ (eplontersen) granted
regulatory approval in the U.S. for the treatment of adults with
polyneuropathy of hereditary transthyretin-mediated amyloidosis
[last accessed 16 May 2024]. Available from:
https://ir.ionispharma.com/news-releases/news-release-details/wainuatm-eplontersen-granted-regulatory-approval-us-treatment.
- Mayo Clinic. International Symposium on Amyloidosis:
Abstracts/Posters [last accessed 21 May 2024] Available from:
https://cveducation.mayo.edu/uploads/ckeditor/attachments/3980/Oral_Abstracts_and_Posters_5.20.24.pdf.
- 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 Jun;10(1):375-389.
- Coelho T, et al. Eplontersen for Hereditary Transthyretin
Amyloidosis With Polyneuropathy. JAMA. 2023;330(15):1448–1458.
- 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.
- Cleveland Clinic. Amyloidosis. Cleveland Clinic website.
Accessed May 21, 2024.
https://my.clevelandclinic.org/health/diseases/23398-amyloidosis.
- Mayo Clinic. Amyloidosis. Mayo Clinic website. Accessed May 21,
2024.
https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178.
US-89473 Last Updated 5/24
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