REG - AstraZeneca PLC - Calquence combination approved in US for 1L MCL

AstraZenecaAnnouncement

17/01/2025 07:00

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RNS Number : 7487T  AstraZeneca PLC  17 January 2025

17 January 2025

 

Calquence plus chemoimmunotherapy approved in the US for

patients with previously untreated mantle cell lymphoma

 

Based on ECHO Phase III trial results which showed more than 16 months of
progression-free survival improvement vs. chemoimmunotherapy alone

 

First and only BTK inhibitor approved for the 1st-line treatment of MCL in the
US

 

AstraZeneca's Calquence (acalabrutinib) in combination with bendamustine and
rituximab has been approved in the US for the treatment of adult patients with
previously untreated mantle cell lymphoma (MCL) who are ineligible for
autologous hematopoietic stem cell transplantation.

 

The approval was granted by the Food and Drug Administration (FDA) after
securing Priority Review
(https://www.astrazeneca.com/media-centre/press-releases/2024/calquence-granted-priority-review-in-the-us-for-patients-with-untreated-mantle-cell-lymphoma.html)
. It was based on results from the ECHO Phase III trial which were presented
at the European Hematology Association 2024 Congress.

 

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL),
often diagnosed at an advanced stage. 1  (#_edn1) (, 2  (#_edn2) ) 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. 3  (#_edn3)

 

Michael Wang, MD, Puddin Clarke Endowed Professor, Director of Mantle Cell
Lymphoma Program of Excellence and principal investigator in the trial, said:
"Managing this aggressive cancer requires maximising efficacy while
maintaining tolerability, especially for elderly patients. Results from the
pivotal ECHO trial highlight the promise of the acalabrutinib combination in
defining a new standard of care, with today's approval underscoring the
transformative potential of this regimen as a first-line treatment for older
patients with mantle cell lymphoma."

 

Dave Fredrickson, Executive Vice-President, Oncology Haematology Business
Unit, AstraZeneca, said: "With today's approval, Calquence provides a critical
new treatment option to mantle cell lymphoma patients in the US, with
Calquence proven to deliver nearly one and a half years of additional time
without disease progression. This approval brings a new and effective
treatment option to those living with this disease and further reinforces our
belief in Calquence as a backbone therapy across multiple blood cancers."

 

Meghan Gutierrez, Chief Executive Officer, Lymphoma Research Foundation, said:
"New treatment options have long been needed in the first-line treatment of
mantle cell lymphoma in the US. Patients with this rare and often aggressive
cancer can experience severe symptoms by the time they are diagnosed - having
an effective therapy that can significantly improve outcomes for patients
early in the treatment process is a much-needed advancement."

 

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 PFS was 66.4 months for patients
treated with the Calquence combination versus 49.6 months with
chemoimmunotherapy alone.

 

This approval additionally converts Calquence's accelerated approval to a full
approval for adult patients with MCL treated with at least one prior therapy,
as granted by the FDA in October 2017.

 

The ECHO trial enrolled patients throughout the COVID-19 pandemic. After
censoring for COVID-19 deaths, PFS was further improved in both arms, with
the Calquence combination reducing the risk of disease progression or death
by 36% (HR 0.64; 95% CI 0.48-0.84). Although OS data were not mature at the
time of the analysis, when censored for COVID-19, a favourable trend was seen
for OS (HR 0.75; 95% CI 0.53-1.04), despite 69% of patients in the
chemoimmunotherapy arm receiving treatment with a BTK inhibitor on relapse or
disease progression.

 

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

 

The US regulatory submission was reviewed under Project Orbis, which provides
a framework for concurrent submission and review of oncology medicines among
participating international partners. As part of Project Orbis, Calquence
plus chemoimmunotherapy is also under review by regulatory authorities in
Australia, Canada, and Switzerland for the same indication. Regulatory
applications are also under review in the EU, Japan, and other countries based
on the ECHO results.

 

Notes

 

Mantle cell lymphoma (MCL)

While MCL patients initially respond to treatment, patients do tend to
relapse. 4  (#_edn4)  MCL comprises about 3-6% of non-Hodgkin lymphomas, with
an annual incidence of 0.5 per 100,000 population in Western countries; in the
US, it is estimated that approximately 4,000 new patients are diagnosed with
MCL each year.(4)(, 5  (#_edn5) )

 

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  (#_edn6)  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 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  (#_edn7)
)

 

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  (#_edn8) In B-cells, BTK signalling results in
activation of pathways necessary for B-cell proliferation, trafficking,
chemotaxis and adhesion.

 

Calquence has been used to treat more than 85,000 patients worldwide 9 
(#_edn9) and 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 in
China and several other countries for the treatment of adult patients with
mantle cell lymphoma (MCL) who have received at least one prior therapy.
Calquence is not currently approved for the treatment of MCL in Japan or the
EU.

 

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
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(https://www.astrazeneca.com/investor-relations.html#Contacts) . For Media
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.

 

(#_ednref1) References

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

(#_ednref2) 2.     National Organization for Rare Disorders. Mantle Cell
Lymphoma. Available at:
https://rarediseases.org/rare-diseases/mantle-cell-lymphoma/. Accessed January
2025.

(#_ednref3) 3.     AstraZeneca 2024. Q3 2024 Financial Results. Available
at: https://www.astrazeneca.com/investor-relations.html
(https://www.astrazeneca.com/investor-relations.html) . Accessed January 2025.

(#_ednref4) 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.

(#_ednref5) 5.     MD Anderson Cancer Center. What to know about mantle
cell lymphoma. Available at:
https://www.mdanderson.org/cancerwise/what-to-know-about-mantle-cell-lymphoma-symptoms-diagnosis-and-treatment.h00-159385101.html.
Accessed January 2025.

(#_ednref6) 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. Accessed January
2025.

(#_ednref7) 7.     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.

(#_ednref8) 8.     Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a
selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).

(#_ednref9) 9.     Data on File, REF-236261. AstraZeneca Pharmaceuticals
LP.

 

 

Adrian Kemp

Company Secretary

AstraZeneca PLC

 

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