REG - AstraZeneca PLC - Update on anselamimab in AL amyloidosis

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RNS Number : 1999R  AstraZeneca PLC  16 July 2025

16 July 2025

 

Update on CARES Phase III clinical programme of anselamimab in light chain
amyloidosis

 

Results did not achieve statistical significance for the primary endpoint in
overall patient population

 

Anselamimab showed highly clinically meaningful improvement vs. placebo in
survival and cardiovascular hospitalisation in prespecified patient subgroup

 

High-level results from the Cardiac Amyloid Reaching for Extended Survival
(CARES) Phase III clinical programme showed that anselamimab, a light chain
depleter antibody, did not achieve statistical significance for the primary
endpoint compared to placebo in patients with Mayo stages IIIa and IIIb light
chain (AL) amyloidosis. The primary endpoint was defined as a hierarchical
combination of time to all-cause mortality (ACM) and frequency of
cardiovascular hospitalisations (CVH). All patients in the clinical programme
received background standard of care for plasma cell dyscrasia.

 

Anselamimab showed highly clinically meaningful improvement in time to ACM and
frequency of CVH in a prespecified subgroup of patients, compared to placebo.
 

 

AL amyloidosis is a rare, systemic and progressive disorder caused by
defective plasma cells in the bone marrow. In AL amyloidosis, abnormal light
chain proteins produced by these plasma cells misfold, aggregate and form
amyloid fibrils that deposit in tissues and organs. Left untreated, the
accumulation of these toxic amyloid deposits, particularly in the heart and
kidneys, can cause progressive organ damage and dysfunction and may lead to
premature death, most commonly due to cardiac failure.(1-3)

 

Ashutosh Wechalekar, MBBS, MD, FRCP, FRCPath, DM, Consultant Haematologist at
University College London Hospitals NHS Foundation Trust (UCLH), Professor of
Medicine and Haematology at University College London (UCL) and lead principal
investigator of the programme, said: "While the study did not meet the primary
endpoint in the overall patient population, results from a pre-defined
subgroup suggest that anselamimab, by targeting and clearing amyloid deposits,
may address a leading cause of organ damage and functional impairment in these
patients. The potential to extend survival and reduce cardiovascular
hospitalisations would represent a practice-changing advancement for this
patient group."

 

Marc Dunoyer, Chief Executive Officer, Alexion, AstraZeneca Rare Disease,
said: "Alexion is pioneering a novel mechanism of action to address organ
damage from existing amyloid deposits in patients with AL amyloidosis, a
devastating disease often diagnosed in advanced stages with poor prognosis.
Anselamimab is the first and only investigational fibril depleter to show
clinical benefit in AL amyloidosis, and these results underscore its potential
to address a critical treatment gap in a prespecified subgroup of patients."

 

Anselamimab was well tolerated, with the majority of events balanced between
the anselamimab treatment arm and the placebo arm.

 

Evaluation of full results is ongoing to further characterise the efficacy and
safety of anselamimab. Alexion plans to share these data with global health
authorities and present them at a forthcoming medical meeting.

 

Notes

 

Light Chain amyloidosis

Light chain (AL) amyloidosis is a systemic and progressive type of amyloidosis
where immunoglobulin light chain proteins are produced abnormally by defective
plasma cells in the bone marrow. These abnormal proteins misfold, aggregate
and form amyloid fibrils that deposit and accumulate in tissues or organs,
particularly in the heart and kidneys. The deposition can cause progressive
damage and may lead to premature death, most commonly due to cardiac
failure.(1,2)

 

In the early stages of the disease, people with AL amyloidosis may experience
a range of vague signs and symptoms that mimic other diseases, which can often
delay the diagnosis. Worldwide, there are an estimated 74,000 patients living
with AL amyloidosis.(4,5)

 

CARES Phase III Clinical Programme

The Cardiac Amyloid Reaching for Extended Survival (CARES) clinical programme
consists of two parallel global, Phase III, randomised, double-blind,
placebo-controlled, multicentre trials evaluating the efficacy and safety of
anselamimab plus standard of care (SoC) in patients with stage IIIa and stage
IIIb light chain (AL) amyloidosis, respectively.(6,7)

 

The primary endpoint is a hierarchical combination of time to all-cause
mortality and frequency of cardiovascular hospitalisations in the overall
patient population across both trials.

 

The CARES clinical programme is the largest prospective investigation in
cardiac AL amyloidosis to date with a total of 406 patients enrolled from 19
countries globally, including 281 patients with stage IIIa and 125 patients
with stage IIIb disease per European modification of the Mayo 2004 staging
system.(6,7)

 

In CARES, newly diagnosed patients planning first-line plasma cell dyscrasia
(PCD) treatment with cyclophosphamide, bortezomib and dexamethasone were
randomised 2:1 to receive either anselamimab or placebo once weekly for the
first four weeks and then every two weeks until study completion. Daratumumab
was permitted but not required as part of the PCD regimen, and approximately
80% of patients in CARES received daratumumab as part of their treatment.

 

Following the primary evaluation treatment period, which concluded 18 months
after the last patient was randomised, all patients had the option to
participate in an open-label extension period receiving anselamimab plus SoC
for up to 24 months.(6,7)

 

Anselamimab

Anselamimab is an investigational, potentially first-in-class anti-fibril
monoclonal antibody designed to improve organ function by reducing or
eliminating amyloid deposits in the tissues and organs of patients living with
AL amyloidosis. By binding with specificity to targets within amino acids on
misfolded amyloid fibrils, anselamimab promotes destruction and clearance of
amyloid deposits, while sparing native free light chains from destruction.
Anselamimab has been granted Fast Track Designation by the US Food and Drug
Administration (FDA) and received Orphan Drug Designation from the US FDA,
European Commission and the Ministry of Health, Labour and Welfare of Japan
for the treatment of AL amyloidosis.

 

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, US.

 

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

 

Contacts

For details on how to contact the Investor Relations Team, please click here
(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.   Desport E, et al. AL Amyloidosis. Orphanet J Rare Dis. 2012;7(54).

2.   Grogan M, et al. Light-chain cardiac amyloidosis: strategies to promote
early diagnosis and cardiac response. Heart. 2017;103:1065-1072.

3.   Mollee P, et al. How to diagnose amyloidosis. Internal Medicine
Journal. 2014;44:7-17.

4.   Wechalekar AD, et al. AL Amyloidosis for Cardiologists; Awareness,
Diagnosis, and Future Prospects. JACC: CardioOncology. 2022;4(4): 427- 441.

5.   Kumar N, et al. Global epidemiology of amyloid light-chain amyloidosis.
Orphanet J Rare Dis. 2022;17(278).

6.   ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of
CAEL-101 in Patients With Mayo Stage IIIa AL Amyloidosis (CARES). NCT
Identifier: NCT04512235. Available here
(https://clinicaltrials.gov/study/NCT04512235?cond=AL%20Amyloidosis&term=CARES&rank=2)
. Accessed June 2025.

7.   ClinicalTrials.gov. A Study to Evaluate the Efficacy and Safety of
CAEL-101 in Patients With Mayo Stage IIIb AL Amyloidosis (CARES). NCT
Identifier: NCT04504825. Available here
(https://clinicaltrials.gov/study/NCT04504825?cond=AL%20Amyloidosis&term=CARES&rank=1)
. Accessed June 2025.

 

Matthew Bowden

Company Secretary

AstraZeneca PLC

 

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