REG - AstraZeneca PLC - Fixed-duration Calquence recommended in EU for CLL

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RNS Number : 4900G  AstraZeneca PLC  29 April 2025

29 April 2025

Fixed-duration Calquence-based regimens recommended for approval

in the EU by CHMP for 1st-line chronic lymphocytic leukaemia

Recommendation based on AMPLIFY Phase III trial which showed Calquence
combinations demonstrated statistically significant and clinically meaningful
improvement in progression-free survival vs. chemoimmunotherapy

A fixed-duration regimen of AstraZeneca's Calquence (acalabrutinib) in
combination with venetoclax, with or without obinutuzumab, has been
recommended for approval in the European Union (EU) for the treatment of adult
patients with previously untreated chronic lymphocytic leukaemia (CLL).

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) based its positive opinion on results from the AMPLIFY
Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/fixed-duration-calquence-plus-venetoclax-demonstrated-superior-pfs-vs-standard-care-previously-untreated-cll-with-77-of-patients-progression-free-3-years-amplify-phase-iii-trial.html)
, which were presented at the American Society of Haematology (ASH) 2024
Annual Meeting and published in The New England Journal of Medicine
(https://www.nejm.org/) .(1)

 

Results showed Calquence plus venetoclax reduced the risk of disease
progression or death by 35% compared to standard-of-care chemoimmunotherapy
(investigator's choice of fludarabine-cyclophosphamide-rituximab or
bendamustine-rituximab; hazard ratio  HR  0.65; 95% confidence interval  CI 
0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab
demonstrated a 58% reduction in the risk of disease progression or death
compared to standard-of-care chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59;
p<0.0001).(2)

 

At three years, 77% of patients treated with Calquence plus venetoclax and 83%
of patients treated with Calquence plus venetoclax and obinutuzumab were
progression free, versus 67% of patients treated with chemoimmunotherapy.(1)
Median progression-free survival (PFS) was not reached for either experimental
arm versus 47.6 months for chemoimmunotherapy.(1)

 

Wojciech Jurczak, MD, Maria Sklodowska-Curie National Institute of Oncology,
Kraków, Poland and investigator for the trial, said: "Chronic lymphocytic
leukaemia is an incurable cancer which means patients live with the disease
and stay on treatment for many years, which can have long-term effects. The
fixed-duration Calquence regimens will allow patients to take breaks from
their treatment, reducing the risk of long-term adverse events and drug
resistance."

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "With this recommendation, Calquence plus venetoclax can
potentially be the only all-oral second-generation BTK inhibitor option
approved in Europe for patients with previously untreated chronic lymphocytic
leukaemia. Calquence has demonstrated efficacy and safety in fixed-duration
and treat-to-progression regimens providing patients and their doctors more
treatment flexibility."

 

CLL is the most common type of leukaemia in adults, with an estimated 27,000
patients diagnosed in the UK, France, Germany, Spain and Italy in 2024.(3)

 

The safety and tolerability of Calquence was consistent with its known
safety profile, and no new safety signals were identified.

 

Regulatory applications for Calquence plus venetoclax, with or without
obinutuzumab, in this setting are currently under review in several countries
based on the AMPLIFY results.

Notes
Chronic lymphocytic leukaemia (CLL)

CLL is the most prevalent type of leukaemia in adults, with over 117,000 new
cases globally in 2021.(4) Although some people with CLL may not experience
any symptoms at diagnosis, others may experience symptoms, such as weakness,
fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and
abdominal pain.(5) In CLL, there is an accumulation of abnormal lymphocytes
within the blood, bone marrow and lymph nodes. As the number of abnormal cells
increases, there is less room within the marrow for the production of normal
white blood cells, red blood cells and platelets.(6) This could result in
infection, anaemia and bleeding. B-cell receptor signalling through BTK is one
of the essential growth pathways for CLL.

AMPLIFY

AMPLIFY is a randomised, global, multi-centre, open-label Phase III trial
evaluating the efficacy and safety of Calquence in combination with
venetoclax, with or without obinutuzumab, compared to investigator's choice of
chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or
bendamustine-rituximab) in adult patients with previously untreated CLL
without del(17p) or TP53 mutation.(7) Patients were randomised 1:1:1 to
receive either Calquence plus venetoclax, Calquence plus venetoclax with
obinutuzumab for a fixed duration or standard-of-care chemoimmunotherapy.(7)
Both the Calquence containing arms were administered for a fixed duration of
14 cycles (each 28 days), and the standard-of-care chemoimmunotherapy was for
6 cycles.(7)

 

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by
an Independent Review Committee and PFS in the Calquence plus venetoclax with
obinutuzumab is a key secondary endpoint.(7) Other key secondary endpoints
include OS and undetectable measurable residual disease.(7) The trial includes
27 countries across North and South America, Europe, Asia and Oceania.(7)

 

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the
COVID-19 pandemic.(7) Patients with blood cancer remain at a
disproportionately high risk of severe outcomes from COVID-19, including
hospitalisation and death compared to the general population.(8)

Calquence

Calquence (acalabrutinib) is a second-generation, selective inhibitor of
Bruton's tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby
inhibiting its activity.(9) In B-cells, BTK signalling results in activation
of pathways necessary for B-cell proliferation, trafficking, chemotaxis and
adhesion.

 

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL)
and small lymphocytic lymphoma (SLL) in the US, Japan and China, approved for
CLL in the EU and many other countries worldwide. Calquence is also approved
for the treatment of adult patients with previously untreated MCL in the US
and other countries. It is also approved for the treatment of adult patients
with MCL who have received at least one prior therapy in China and several
other countries. Calquence is not currently approved for the treatment of MCL
in Japan.

 

As part of an extensive clinical development programme, Calquence is currently
being evaluated as a single treatment and in combination with standard-of-care
chemoimmunotherapy for patients with multiple B-cell blood cancers, including
CLL, MCL and diffuse large B-cell lymphoma.

AstraZeneca in haematology

AstraZeneca is pushing the boundaries of science to redefine care in
haematology. Our goal is to help transform the lives of patients living with
malignant, rare and other related haematologic diseases through innovative
medicines and approaches that are shaped by insights from patients, caregivers
and physicians.

 

In addition to our marketed products, we are spearheading the development of
novel therapies designed to target underlying drivers of disease across
multiple scientific platforms. Our acquisitions of Alexion, with expertise in
rare, non-malignant blood disorders, and Gracell Biotechnologies Inc.,
pioneers of autologous cell therapies, expand our haematology pipeline and
enable us to reach more patients with high unmet needs through the end-to-end
discovery, development and delivery of novel therapies.

 

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide
cures for cancer in every form, following the science to understand cancer and
all its complexities to discover, develop and deliver life-changing medicines
to patients.

 

The Company's focus is on some of the most challenging cancers. It is through
persistent innovation that AstraZeneca has built one of the most diverse
portfolios and pipelines in the industry, with the potential to catalyse
changes in the practice of medicine and transform the patient experience.

 

AstraZeneca has the vision to redefine cancer care and, one day, eliminate
cancer as a cause of death.

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
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.

 

References

1.   Brown J, et al. Fixed-Duration Acalabrutinib Combinations in Untreated
Chronic Lymphocytic Leukemia. NEJM. 2025;392:748-762.

2.   Brown, J et al. Fixed-Duration Acalabrutinib plus Venetoclax with or
without Obinutuzumab versus Chemoimmunotherapy for First-Line Treatment of
Chronic Lymphocytic Leukemia: Interim Analysis of the Multicenter, Open-label,
Randomized, Phase 3 AMPLIFY Trial. Presented at ASH 2024. Abstract 1009. 2024.

3.   AstraZeneca 2024. Full Year and Q4 2024 Financial Results Epidemiology
Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html
(https://www.astrazeneca.com/investor-relations.html) . Accessed April 2025.

4.   Global Burden of Disease Collaborative Network's "Global Burden of
Disease Study 2021 (GBD 2021)" published by the Institute for Health Metrics
and Evaluation (IHME) in Seattle, United States, in 2024. Accessed April 2025.

5.   American Cancer Society. Signs and Symptoms of Chronic Lymphocytic
Leukemia. Available at:
https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html
(https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html)
. Accessed April 2025.

6.   National Cancer Institute. Chronic lymphocytic leukemia treatment
(PDQ(®))-Patient version. Available at:
https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq
(https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq) . Accessed
April 2025.

7.   ClinicalTrials.gov. Study of Acalabrutinib (ACP-196) in Combination
With Venetoclax (ABT-199), With and Without Obinutuzumab (GA101) Versus
Chemoimmunotherapy for Previously Untreated CLL (AMPLIFY). Available at:
https://clinicaltrials.gov/study/NCT03836261
(https://clinicaltrials.gov/study/NCT03836261) . Accessed April 2025.

8.   Dube S, et al. Continued Increased Risk of COVID-19 Hospitalisation and
Death in Immunocompromised Individuals Despite Receipt of ≥4 Vaccine Doses:
Updated 2023 Results from INFORM, a Retrospective Health Database Study in
England. Poster P0409 at ECCMID 2024.

9.   Wu J, et al. Acalabrutinib (ACP-196): a selective second-generation BTK
inhibitor. J Hematol Oncol. 2016;9(21).

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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