TIDMAZN
RNS Number : 2853U
AstraZeneca PLC
21 November 2019
21 November 2019 18:10 GMT
Calquence approved in the US
for adult patients with chronic lymphocytic leukaemia
Two Phase III Calquence trials demonstrated superior
progression-free survival across multiple settings while
maintaining favourable tolerability
Calquence combined with obinutuzumab and as monotherapy
reduced
the risk of disease progression or death by 90% and 80%,
respectively in ELEVATE-TN
AstraZeneca today announced that the US Food and Drug
Administration (FDA) has approved Calquence (acalabrutinib) for
adult patients with chronic lymphocytic leukaemia (CLL) or small
lymphocytic lymphoma (SLL).(1) The US approval was granted under
the FDA's Real-Time Oncology Review and newly established Project
Orbis programmes.
The approval is based on positive results from the interim
analyses of two Phase III clinical trials, ELEVATE-TN in patients
with previously untreated CLL and ASC in patients with relapsed or
refractory CLL. Together, the trials showed that Calquence in
combination with obinutuzumab or as a monotherapy significantly
reduced the relative risk of disease progression or death versus
the comparator arms in both 1st-line and relapsed or refractory
CLL. Across both trials, the safety and tolerability of Calquence
were consistent with its established profile.(1)
Dave Fredrickson, Executive Vice President, Oncology Business
Unit said: "With over 20,000 new cases anticipated this year in the
US alone, today's approval of Calquence provides new hope for
patients with one of the most common types of adult leukaemia,
offering outstanding efficacy and a favourable tolerability
profile. The chronic lymphocytic leukaemia patient population is
known to face multiple comorbidities, and tolerability is a
critical factor in their treatment."
Dr Jeff Sharman, Director of Research at Willamette Valley
Cancer Institute, Medical Director of Hematology Research for The
US Oncology Network, and a lead author of the ELEVATE-TN trial,
said: "Tolerability remains an issue in the current treatment
landscape of chronic lymphocytic leukaemia, which may require
ongoing therapy for many years. In the ELEVATE-TN and ASC trials
comparing Calquence to commonly used treatment regimens, Calquence
demonstrated a clinically meaningful improvement in
progression-free survival in patients across multiple settings,
while maintaining its favourable tolerability and safety
profile."
The results of the interim analysis of the ELEVATE-TN trial will
be presented at the upcoming American Society of Hematology
congress.(2)
The trial showed a statistically significant and clinically
meaningful improvement in progression-free survival (PFS) for
patients treated with either Calquence in combination with
obinutuzumab or Calquence monotherapy versus chlorambucil
chemotherapy plus obinutuzumab, a current standard-of-care
combination used in the control arm.(1)
In the Calquence combination arm, risk of disease progression or
death was reduced by 90% (HR 0.10; 95% CI, 0.06-0.17, p<0.0001)
and in the monotherapy arm it was reduced by 80% (HR 0.20; 95% CI,
0.13-0.30, p<0.0001).(1)
The median time to disease progression for patients treated with
Calquence in combination with obinutuzumab or as a monotherapy has
not yet been reached versus 22.6 months (95% CI, 20-28) for
chlorambucil plus obinutuzumab.(1)
ELEVATE-TN safety overview (most common ARs, >=15%):(1)
Calquence plus Calquence monotherapy Chlorambucil plus
obinutuzumab (n=179) obinutuzumab
(n=178) (n=169)
Any Grade Any Grade Any Grade
Adverse reaction >=3 >=3 >=3
------- --------- ---------- ------------- -------- ---------
Infection 69% 22% 65% 14% 46% 13%
------- --------- ---------- ------------- -------- ---------
Neutropenia 53% 37% 23% 13% 78% 50%
------- --------- ---------- ------------- -------- ---------
Anemia 52% 12% 53% 10% 54% 14%
------- --------- ---------- ------------- -------- ---------
Thrombocytopenia 51% 12% 32% 3.4% 61% 16%
------- --------- ---------- ------------- -------- ---------
Headache 40% 1.1% 39% 1.1% 12% 0
------- --------- ---------- ------------- -------- ---------
Diarrhoea 39% 4.5% 35% 0.6% 21% 1.8%
------- --------- ---------- ------------- -------- ---------
Musculoskeletal
pain 37% 2.2% 32% 1.1% 16% 2.4%
------- --------- ---------- ------------- -------- ---------
Fatigue 34% 2.2% 23% 1.1% 24% 1.2%
------- --------- ---------- ------------- -------- ---------
Bruising 31% 0 21% 0 5% 0
------- --------- ---------- ------------- -------- ---------
Rash 26% 2.2% 25% 0.6% 9% 0.6%
------- --------- ---------- ------------- -------- ---------
Arthralgia 22% 1% 16% 0.6% 4.7% 1.2%
------- --------- ---------- ------------- -------- ---------
Dizziness 20% 0 12% 0 7% 0
------- --------- ---------- ------------- -------- ---------
Hemorrhage 20% 1.7% 20% 1.7% 6% 0
------- --------- ---------- ------------- -------- ---------
Nausea 20% 0 22% 0 31% 0
------- --------- ---------- ------------- -------- ---------
Lymphocytosis 12% 11% 16% 15% 0.6% 0.6%
------- --------- ---------- ------------- -------- ---------
Includes multiple ADR terms.
In patients treated with the combination of Calquence plus
obinutuzumab, adverse reactions (ARs) led to treatment
discontinuation in 11% of patients and a dose reduction of
Calquence in 7% of patients. In the monotherapy arm, ARs led to
discontinuation in 10% and dose reduction in 4% of patients.(1) In
the control arm, ARs led to regimen discontinuation in 14% of
patients with a dose reduction of chlorambucil in 28% of
patients.(3) There were no dose reductions for obinutuzumab.(1,)
(3)
In 1,029 patients with haematologic malignancies who were
treated with Calquence 100mg approximately every 12 hours across
multiple clinical trials, where 88% received treatment for at least
six months and 79% received treatment for at least one year,
serious or Grade >=3 infections occurred in 19%, and Grade 3
atrial fibrillation and flutter occurred in 1.1% of patients. In
the same patient population, major haemorrhage occurred in 3.0%
(serious or Grade >=3 bleeding or any central nervous system
bleeding), with fatal haemorrhage occurring in 0.1% of patients.
Second primary malignancies (all grades) including skin cancers
occurred in 12% of patients.(1)
The US approval is among the first to be granted under Project
Orbis, an initiative of the US FDA Oncology Center of Excellence,
which provides a framework for concurrent submission and review of
oncology medicines among international partners. The FDA, the
Australian Therapeutic Goods Administration, and Health Canada
collaborated on this review. (4)
About Calquence
In the US, Calquence (acalabrutinib) is indicated for the
treatment of adult patients with chronic lymphocytic leukaemia
(CLL)/small lymphocytic lymphoma (SLL). In the US, Canada,
Australia, Brazil, Qatar, the United Arab Emirates, Mexico,
Argentina, Singapore, Chile, and recently India, Calquence is
indicated for adult patients with mantle cell lymphoma (MCL) who
have received at least one prior therapy. Approved under
accelerated review in the US, continued approval for previously
treated MCL is contingent upon verification and confirmation of
clinical benefit in confirmatory trials.
Calquence is a next-generation selective inhibitor of Bruton's
tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby
inhibiting its activity.(1,5,6,7) In B-cells, BTK signalling
results in activation of pathways necessary for B-cell
proliferation, trafficking, chemotaxis, and adhesion.(1)
As part of an extensive clinical development programme,
AstraZeneca and Acerta Pharma are currently evaluating Calquence in
23 company-sponsored clinical trials. Calquence is being developed
for the treatment of multiple B-cell blood cancers including CLL,
MCL, diffuse large B-cell lymphoma, Waldenström macroglobulinaemia
and follicular lymphoma and other haematologic malignancies.
Several Phase III clinical trials in CLL are ongoing, including
ASC, ELEVATE-TN, ELEVATE-RR (ACE-CL-006) evaluating Calquence
versus ibrutinib in patients with previously treated high-risk CLL,
and ACE-CL-311 evaluating Calquence in combination with venetoclax
and with/without obinutuzumab versus chemoimmunotherapy in patients
with previously untreated CLL without 17p deletion or TP53
mutation.
About ELEVATE-TN
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label
Phase III trial evaluating the safety and efficacy of Calquence in
combination with obinutuzumab, a CD20 monoclonal antibody, or
Calquence alone versus chlorambucil, a chemotherapy, 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 or unacceptable toxicity) in
combination with obinutuzumab. Patients in the third arm received
Calquence monotherapy (100mg twice daily until disease progression
or unacceptable toxicity).(1,8)
The primary endpoint is 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
is IRC-assessed PFS in the Calquence monotherapy arm compared to
the chlorambucil and obinutuzumab arm. Other secondary endpoints
include objective response rate, time to next treatment and overall
survival.(1,8)
About ASCEND
ASCEND (ACE-CL-309) is a global, randomised, multicentre,
open-label Phase III trial evaluating the efficacy of Calquence in
previously treated patients with CLL. In the trial, 310 patients
were randomised (1:1) into two arms. Patients in the first arm
received Calquence monotherapy (100mg twice daily until disease
progression or unacceptable toxicity). Patients in the second arm
received investigator's choice of either rituximab, a CD20
monoclonal antibody, in combination with idelalisib, a PI3K
inhibitor, or rituximab in combination with bendamustine, a
chemotherapy.(1,9)
The primary endpoint is PFS assessed by an IRC, and key
secondary endpoints include physician-assessed PFS, IRC- and
physician-assessed overall response rate and duration of response,
as well as overall survival, patient-reported outcomes and time to
next treatment.(1,9)
About CLL
Chronic lymphocytic leukaemia (CLL) is one of the most common
types of leukaemia in adults, with an estimated 105,000 new cases
globally each year and 20,720 new cases in the US in 2019, and the
number of people living with CLL is expected to grow with improved
treatment as patients live longer with the disease.(10,11,12,13) In
CLL, too many blood stem cells in the bone marrow become abnormal
lymphocytes and these abnormal cells have difficulty fighting
infections.(10) As the number of abnormal cells grows there is less
room for healthy white blood cells, red blood cells and
platelets.(10) This could result in anaemia, infection and
bleeding.(10) B-cell receptor signalling through BTK is one of the
essential growth pathways for CLL.
About AstraZeneca in haematology
Leveraging its strength in oncology, AstraZeneca has established
haematology as one of four key oncology disease areas of focus. The
Company's haematology franchise includes two US FDA-approved
medicines and a robust global development programme for a broad
portfolio of potential blood cancer treatments. Acerta Pharma
serves as AstraZeneca's haematology research and development arm.
AstraZeneca partners with like-minded science-led companies to
advance the discovery and development of therapies to address unmet
need.
About AstraZeneca in oncology
AstraZeneca has a deep-rooted heritage in oncology and offers a
quickly-growing portfolio of new medicines that has the potential
to transform patients' lives and the Company's future. With at
least six new medicines to be launched between 2014 and 2020, and a
broad pipeline of small molecules and biologics in development, the
Company is committed to advance oncology as a key growth driver for
AstraZeneca focused on lung, ovarian, breast and blood cancers. In
addition to AstraZeneca's main capabilities, the Company is
actively pursuing innovative partnerships and investments that
accelerate the delivery of our strategy, as illustrated by the
investment in Acerta Pharma in haematology.
By harnessing the power of four scientific platforms -
Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response
and Antibody Drug Conjugates - and by championing the development
of personalised combinations, AstraZeneca has the vision to
redefine cancer treatment and, one day, eliminate cancer as a cause
of death.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company
that focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three therapy areas - Oncology, Cardiovascular, Renal and
Metabolism, and Respiratory. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and follow the
Company on Twitter @AstraZeneca.
Media Relations
Gonzalo Viña +44 203 749 5916
Rob Skelding Oncology +44 203 749 5821
Rebecca Einhorn Oncology +1 301 518 4122
Matt Kent BioPharmaceuticals +44 203 749 5906
Jennifer Hursit Other +44 203 749 5762
Christina Malmberg Hägerstrand Sweden +46 8 552 53 106
Michele Meixell US +1 302 885 2677
Investor Relations
Thomas Kudsk Larsen +44 203 749 5712
Henry Wheeler Oncology +44 203 749 5797
Christer Gruvris BioPharmaceuticals (CV, metabolism) +44 203 749 5711
Nick Stone BioPharmaceuticals (Renal), ESG +44 203 749 5716
Josie Afolabi BioPharmaceuticals (Respiratory), other medicines +44 203 749 5631
Craig Marks Finance, fixed income +44 7881 615 764
Jennifer Kretzmann Corporate access, retail investors +44 203 749 5824
US toll-free +1 866 381 72 77
References
1. CALQUENCE(R) (acalabrutinib) [prescribing information].
Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
2. Sharman JP, et al. ELEVATE TN: Phase 3 Study of Acalabrutinib
Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil
(Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic
Leukemia (CLL). Abstract 31 at: American Society of Hematology 2019
Annual Meeting and Exposition. Available online. Accessed November
2019.
3. Data on File. REF-64711. AstraZeneca Pharmaceuticals LP,
Wilmington, DE.
4. US Food and Drug Administration. Project Orbis. Available
online. Accessed November 2019.
5. Wu J, Zhang M & Liu D. Acalabrutinib (ACP-196): a
selective second-generation BTK inhibitor. J Hematol Oncol.
2016;9(21).
6. Khan Y & O'Brien S. Acalabrutinib and its use in
treatment of chronic lymphocytic leukemia. Future Oncol.
2018;15(6).
7. Byrd JC, et al. Acalabrutinib (ACP-196) in Relapsed Chronic
Lymphocytic Leukemia. N Engl J Med. 2016; 374:323-332.
8. ClinicalTrials.gov. Elevate CLL TN: Study of Obinutuzumab +
Chlorambucil, Acalabrutinib (ACP-196) + Obinutuzumab, and
Acalabrutinib in Subjects With Previously Untreated CLL.
NCT02475681. Available online. Accessed November 2019.
9. ClinicalTrials.gov. A Study of Acalabrutinib vs
Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine
Plus Rituximab in R/R CLL. NCT02970318. Available online. Accessed
November 2019.
10. National Cancer Institute. Chronic Lymphocytic Leukemia
Treatment (PDQ(R) )-Patient Version. Available online. Accessed
November 2019.
11. Global Burden of Disease Cancer Collaboration. Global,
Regional, and National Cancer Incidence, Mortality, Years of Life
Lost, Years Lived With Disability, and Disability-Adjusted
Life-Years for 29 Cancer Groups, 1990 to 2016. JAMA Oncol.
2018;4(11):1553-1568.
12. American Cancer Society. Key Statistics for Chronic
Lymphocytic Leukemia. Available online. Accessed November 2019.
13. Jain N, et al. Prevalence and Economic Burden of Chronic
Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies.
Blood. 2015;126:871.
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 or visit www.rns.com.
END
MSCBBBRTMBITBPL
(END) Dow Jones Newswires
November 21, 2019 13:15 ET (18:15 GMT)
Grafico Azioni Astrazeneca (LSE:AZN)
Storico
Da Mar 2024 a Apr 2024
Grafico Azioni Astrazeneca (LSE:AZN)
Storico
Da Apr 2023 a Apr 2024