REG - AstraZeneca PLC - Calquence Japan approval for treatment-naïve CLL

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28/12/2022 07:15

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RNS Number : 9726K  AstraZeneca PLC  28 December 2022

28 December 2022 07:05 GMT

 

Calquence approved in Japan for adults with

treatment-naïve chronic lymphocytic leukaemia

 

Calquence significantly increased the time patients lived without disease
progression or death vs. chemoimmunotherapy

 

AstraZeneca's Calquence (acalabrutinib), a selective Bruton's tyrosine kinase
(BTK) inhibitor, has been approved in Japan for the treatment of adult
patients with treatment-naïve chronic lymphocytic leukaemia (CLL) (including
small lymphocytic lymphoma  SLL ). Calquence was previously approved
(https://www.astrazeneca.com/media-centre/press-releases/2021/calquence-approved-in-japan-for-cll.html)
in Japan for the treatment of adults with relapsed or refractory CLL.

 

The approval by the Japanese Ministry of Health, Labour and Welfare (MHLW) was
based on positive results from two clinical trials, including the ELEVATE-TN
Phase III trial in adults with treatment-naïve CLL. This trial showed that
Calquence combined with obinutuzumab or as monotherapy demonstrated a
significantly improved progression-free survival (PFS) when compared with the
chemotherapy-based combination of chlorambucil and obinutuzumab.(1,2) Data
from the interim analysis of ELEVATE-TN was published in The Lancet
(https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30262-2/fulltext)
in 2020.(2) Additionally, a Phase I trial in treatment-naïve Japanese
patients with CLL was also submitted to MHLW supporting the approval, with the
trial showing an overall response rate of 88.9% (95% CI: 63.2, 98.8%) for
Calquence alone and 100% (95% CI: 66.4, 100%) for Calquence combined with
obinutuzumab.

 

CLL is the most prevalent type of adult leukaemia across the globe but is
considered a rare disease in Japan and East Asia, with fewer than one person
newly diagnosed per 100,000 persons per year across Japan.(3-5)

 

Koji Izutsu, MD, PhD, Department Head, Department of Hematology, National
Cancer Center Hospital, Tokyo, Japan, said: "Results from ELEVATE-TN and our
local Japanese trial confirm that Calquence provides a significant improvement
in progression-free survival compared with chemotherapy-based combination of
chlorambucil and obinutuzumab for patients with treatment-naïve chronic
lymphocytic leukaemia. Today's approval marks great progress for physicians
and patients in Japan, as they can now be treated with Calquence earlier in
their treatment journey."

 

Dave Fredrickson, Executive Vice President, Oncology Business Unit,
AstraZeneca, said: "The approval of Calquence in Japan for those with
treatment-naïve chronic lymphocytic leukaemia now offers more patients a
next-generation Bruton's tyrosine kinase inhibitor that has proven longer-term
efficacy and tolerability compared to standards of care. With this approval,
people living with chronic lymphocytic leukaemia in Japan can now potentially
benefit from our medicine in an earlier setting."

 

Updated results of the ELEVATE-TN Phase III trial after a median follow-up of
approximately five years were presented
(https://www.astrazeneca.com/media-centre/press-releases/2022/calquence-plus-obinutuzumab-demonstrated-sustained-survival-benefit-in-1st-line-chronic-lymphocytic-leukaemia.html)
earlier this year. These results showed that Calquence maintained a
statistically significant PFS benefit versus chlorambucil plus obinutuzumab,
and a safety and tolerability profile consistent with the known profile for
Calquence. At a median follow-up of 58.2 months, Calquence plus obinutuzumab
reduced the risk of disease progression or death by 89% (based on a hazard
ratio  HR  of 0.11, 95% confidence interval  CI  0.07-0.16) and as a
monotherapy by 79% (based on a HR of 0.21, 95% CI 0.15-0.30), compared with
chlorambucil plus obinutuzumab.(1)

 

Calquence is approved
(https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-approved-in-the-us-for-adult-patients-with-chronic-lymphocytic-leukaemia-21112019.html)
 for the treatment of CLL and SLL in the US and is approved
(https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/calquence-approved-in-the-eu-for-cll.html)
for the treatment of CLL in the EU and in several other countries worldwide in
the treatment-naïve and relapsed or refractory settings. Calquence is also
approved in the US 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.

 

Notes

 

CLL

CLL is the most prevalent type of leukaemia in adults, with over 100,000 new
cases globally in 2019, but is considered a rare disease in Japan and East
Asia, with fewer than one person newly diagnosed per 100,000 persons per year
across Japan.(3-5) 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.(6)

 

In CLL, there is an accumulation of abnormal lymphocytes within the bone
marrow. 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.(7) This could result in anaemia, infection and bleeding. B-cell
receptor signalling through BTK is one of the essential growth pathways for
CLL.

 

ELEVATE-TN

ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III
trial evaluating the safety and efficacy of Calquence alone or in
combination with obinutuzumab versus chlorambucil in combination with
obinutuzumab in previously untreated patients with CLL. In the trial, 535
patients were randomised (1:1:1) into three arms. Patients in the first arm
received chlorambucil in combination with obinutuzumab. Patients in the
second arm received Calquence (100mg twice daily until disease progression)
in combination with obinutuzumab. Patients in the third arm
received Calquence monotherapy (100mg twice daily until disease
progression).(8)

 

The primary endpoint was PFS in the Calquence and obinutuzumab arm compared
to the chlorambucil and obinutuzumab arm, assessed by an independent review
committee (IRC), and a key secondary endpoint was IRC-assessed PFS in
the Calquence monotherapy arm compared to the chlorambucil and obinutuzumab
arm. Other secondary endpoints included overall response rate, time to next
treatment, overall survival and investigator assessed PFS. After interim
analysis, assessments were by investigator only.(8)

 

Initial results from the ELEVATE-TN Phase III trial were presented in December
2019 at the American Society of Hematology Annual Meeting and Exhibition. The
trial met its primary endpoint (IRC-assessed PFS with Calquence plus
obinutuzumab versus chlorambucil plus obinutuzumab) at the data cut-off for
the interim analysis after a median follow-up of 28.3 months. The findings,
along with previously reported data from the ASCEND Phase III trial in
relapsed or refractory CLL, supported the approvals of Calquence by the US
FDA and the Australian Therapeutic Goods Administration for the treatment of
adult patients with CLL or SLL and by the European Medicines Agency (EMA) and
Health Canada for CLL.

 

Calquence

Calquence (acalabrutinib) is a next-generation, selective inhibitor of
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 CLL and SLL in the US, approved
for CLL in the EU and many other countries worldwide and approved in Japan for
relapsed or refractory CLL and SLL.

 

In the US and several other countries, Calquence is also approved for the
treatment of adult patients with MCL who have received at least one prior
therapy. The US MCL indication is approved under accelerated approval based on
overall response rate. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in
confirmatory trials. Calquence is not currently approved for the treatment
of MCL in Europe or Japan.

 

As part of an extensive clinical development programme, AstraZeneca and
Acerta Pharma are currently evaluating Calquence in more than 20
company-sponsored clinical trials. Calquence is being evaluated for the
treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large
B-cell lymphoma, Waldenström's macroglobulinaemia, marginal zone lymphoma and
other haematologic malignancies.

 

AstraZeneca in haematology

AstraZeneca is pushing the boundaries of science to redefine care in
haematology. We have expanded our commitment to patients with haematologic
conditions, not only in oncology but also in rare diseases with the
acquisition of Alexion, allowing us to reach more patients with high unmet
needs. By applying our deep understanding of blood cancers, leveraging our
strength in solid tumour oncology and delivering on Alexion's pioneering
legacy in complement science to provide innovative medicines for rare
diseases, we are pursuing the end-to-end development of novel therapies
designed to target underlying drivers of disease.

 

By targeting haematologic conditions with high unmet medical needs, we aim to
deliver innovative medicines and approaches to improve patient outcomes. Our
goal is to help transform the lives of patients living with malignant, rare
and other related haematologic diseases, shaped by insights from patients,
caregivers and physicians to have the most meaningful impact.

 

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 operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
Please visit astrazeneca.com (http://www.astrazeneca.com/)  and follow the
Company on Twitter @AstraZeneca (https://twitter.com/AstraZeneca) .

 

Contacts

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.

 

References

1.  Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± Obinutuzumab vs
Obinutuzumab + Chlorambucil in Treatment-Naïve Chronic Lymphocytic Leukemia:
5-Year Follow-up of ELEVATE-TN [abstract and poster]. Presented at: American
Society for Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2022. Abstract
ID: 7539.

2.  Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without
obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic
lymphocytic leukaemia (ELEVATE-TN): a randomized, controlled, phase 3
trial. Lancet. 2020;395:1278-1291. doi:10.1182/blood-2019-128404.

3.  Yao Y, Lin X, Li F, et al. The global burden and attributable risk
factors of chronic lymphocytic leukemia in 204 countries and territories from
1990 to 2019: analysis based on the global burden of disease study
2019. Biomed Eng Online. 2022;1: 4. doi: 10.1186/s12938-021-00973-6.

4.  Mahlich J, Okamoto S, Tsubota A. Cost of Illness of Japanese Patients
with Chronic Lymphocytic Leukemia (CLL), and Budget Impact of the Market
Introduction of Ibrutinib. Pharmacoecon Open. 2017;1(3):195-202.
doi:10.1007/s41669-017-0024-5.

5.  National Cancer Institute Cancer Information Service. Chronic Lymphocytic
Leukemia/Small Lymphocytic Lymphoma. Available at:
https://ganjoho.jp/public/cancer/CLL/index.html. Accessed November 2022
(https://ganjoho.jp/public/cancer/CLL/index.html.%20Accessed%20January%202021)
.

6.  American Cancer Society. Signs and Symptoms of Chronic Lymphocytic
Leukemia. Accessed online
(https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/detection-diagnosis-staging/signs-symptoms.html)
. Accessed November 2022.

7.  National Cancer Institute. Chronic lymphocytic leukemia treatment
(PDQ®)-Patient version. Accessed online
(https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq) . Accessed
November 2022.

8.  ClinicalTrials.gov. ELEVATE CLL TN: Study of Obinutuzumab + Chlorambucil,
Acalabrutinib (ACP-196) + Obinutuzumab, and Acalabrutinib in Subjects With
Previously Untreated CLL. NCT identifier: NCT02475681.
https://clinicaltrials.gov/ct2/show/NCT02475681. Accessed November 2022.

9.  Wu J, Zhang M, Liu D. 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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