REG - AstraZeneca PLC - Calquence recommended for EU approval in 1L MCL

AstraZenecaAnnouncement

31/03/2025 07:15

For best results when printing this announcement, please click on link below:
https://newsfile.refinitiv.com/getnewsfile/v1/story?guid=urn:newsml:reuters.com:20250331:nRSe7954Ca&default-theme=true

RNS Number : 7954C  AstraZeneca PLC  31 March 2025

31 March 2025

 

Calquence plus chemoimmunotherapy recommended for approval in the EU by CHMP
as first and only BTK inhibitor for 1st-line mantle cell lymphoma

 

Recommendation based on ECHO Phase III trial results which demonstrated over
16 months of progression-free survival improvement vs. chemoimmunotherapy
alone

 

AstraZeneca's Calquence (acalabrutinib) in combination with bendamustine and
rituximab has been recommended for approval in the European Union (EU) for the
treatment of adult patients with previously untreated mantle cell lymphoma
(MCL) who are not eligible for autologous hematopoietic stem cell
transplantation.

 

The Committee for Medicinal Products for Human Use (CHMP) of the European
Medicines Agency (EMA) based its positive opinion on the results from the ECHO
Phase III trial
(https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-plus-chemoimmunotherapy-reduced-the-risk-of-disease-progression-or-death-by-27-percent.html)
which were presented at the European Hematology Association 2024 Congress.

 

Results from the ECHO trial showed Calquence plus bendamustine and rituximab
reduced the risk of disease progression or death by 27% compared to
standard-of-care chemoimmunotherapy (hazard ratio  HR  0.73; 95% confidence
interval  CI  0.57-0.94; p=0.016). Median progression-free survival (PFS) was
66.4 months for patients treated with the Calquence combination versus 49.6
with chemoimmunotherapy alone.

 

This recommendation for Calquence as a combination treatment in the 1st-line
MCL setting follows the recent CHMP positive opinion
(https://www.ema.europa.eu/en/medicines/human/variation/calquence) for
Calquence as a monotherapy for the treatment of adult patients with relapsed
or refractory MCL.

 

Martin Dreyling, MD, Department of Medicine, University Hospital LMU Munich,
and investigator in the trial, said: "Results from the pivotal ECHO trial
demonstrated the significant benefits of the Calquence combination in managing
this rare and aggressive cancer. Today's recommendation is an important
advance within the mantle cell lymphoma first-line treatment landscape,
especially for older patients who need a balance of efficacy and
tolerability."

 

Susan Galbraith, Executive Vice President, Oncology Haematology R&D,
AstraZeneca, said: "Today's positive recommendation from the CHMP further
reinforces the potential of Calquence to advance first-line treatment options
in mantle cell lymphoma, with the Calquence combination demonstrating an
almost one and a half year improvement in progression-free survival in this
setting. If approved, Calquence has the potential to transform the standard of
care as the first BTK inhibitor approved for these patients in Europe."

 

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma, often
diagnosed at an advanced stage.(1,2) It is estimated that more than 6,000
patients were diagnosed with MCL 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.

 

Calquence plus bendamustine and rituximab is approved in the US and several
other countries in this setting based on the ECHO results. Regulatory
applications are currently under review in Japan and several other countries
in this indication.

 

Notes

 

Mantle cell lymphoma (MCL)

While MCL patients initially respond to treatment, patients do tend to
relapse.(4) MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual
incidence of 0.5 per 100,000 population in Western countries; It is estimated
that there are more than 21,000 patients diagnosed with MCL in the US, UK,
France, Germany, Spain, Italy, Japan and China.(5)

 

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III
trial evaluating the efficacy and safety of Calquence plus bendamustine and
rituximab compared to SoC chemoimmunotherapy (bendamustine and rituximab) in
adult patients at or over 65 years of age (n=635) with previously untreated
MCL.(6) Patients were randomised 1:1 to receive either Calquence or placebo
administered orally twice per day, continuously, until disease progression or
unacceptable toxicity. Additionally, all patients received six 28-day cycles
of bendamustine on days 1 and 2 and rituximab on day 1 of each cycle, followed
by rituximab maintenance for two years if patients achieved a response after
induction therapy.(6)

( )

The primary endpoint is PFS assessed by an Independent Review Committee; other
efficacy endpoints include overall survival (OS), overall response rate (ORR),
duration of response (DoR) and time to response (TTR).(6) The trial was
conducted in 27 countries across North and South America, Europe, Asia and
Oceania.(6)

 

The ECHO trial enrolled patients from May 2017 to March 2023, continuing
through the COVID-19 pandemic. Prespecified PFS and OS analyses censoring for
COVID-19 deaths were conducted to assess the impact of COVID-19 on the study
outcome in alignment with the FDA. 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.(6,7,8)

 

Calquence

Calquence (acalabrutinib) is a second-generation, selective inhibitor of
Bruton's tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby
inhibiting its activity.(8) 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 and Japan, approved for CLL in
the EU and many other countries worldwide and approved in China for relapsed
or refractory CLL and SLL. 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 the US, 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
contacts, click here (https://www.astrazeneca.com/media-centre/contacts.html)
.

 

References

1.     Lymphoma Research Foundation. Mantle Cell Lymphoma. Available at:
https://lymphoma.org/aboutlymphoma/nhl/mcl/
(https://lymphoma.org/aboutlymphoma/nhl/mcl/) . Accessed March 2025.

2.     National Organization for Rare Disorders. Mantle Cell Lymphoma.
Available at: https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/
(https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/) . Accessed
March 2025.

3.     AstraZeneca 2024. Q3 2024 Financial Results. Available at:
https://www.astrazeneca.com/investor-relations.html
(https://www.astrazeneca.com/investor-relations.html) . Accessed March 2025.

4.     Cheah C, Seymour J, Wang ML. Mantle cell lymphoma. J Clin Oncol.
2016;34(11):1256-1269. doi: 10.1200/JCO.2015.63.5904.

5.     Lynch DT, Koya S, Acharya U, et al. Mantle Cell Lymphoma. Available
at: https://www.ncbi.nlm.nih.gov/books/NBK536985
(https://www.ncbi.nlm.nih.gov/books/NBK536985) . Accessed March 2025.

6.     ClinicalTrials.gov. A Study of BR Alone Versus in Combination With
Acalabrutinib in Subjects With Previously Untreated MCL. Available at:
https://clinicaltrials.gov/study/NCT02972840.
(https://clinicaltrials.gov/study/NCT02972840.%20Accessed%20November%202024)
Accessed March 2025.

7.     Luque-Paz D, et al. B-cell malignancies and COVID-19: a narrative
review. Clin Microbiology and Infection. 2023; 29(332-337).

8.     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

 

This information is provided by RNS, the news service of the London Stock Exchange. RNS is approved by the Financial Conduct Authority to act as a Primary Information Provider in the United Kingdom. Terms and conditions relating to the use and distribution of this information may apply. For further information, please contact
rns@lseg.com (mailto:rns@lseg.com)
 or visit
www.rns.com (http://www.rns.com/)
.

RNS may use your IP address to confirm compliance with the terms and conditions, to analyse how you engage with the information contained in this communication, and to share such analysis on an anonymised basis with others as part of our commercial services. For further information about how RNS and the London Stock Exchange use the personal data you provide us, please see our
Privacy Policy (https://www.lseg.com/privacy-and-cookie-policy)
.   END  MSCPKCBPCBKDCNB