# AstraZeneca plc Calquence granted US Breakthrough Therapy Designation

- Link: https://www.directorstalkinterviews.com/astrazeneca-plc-calquence-granted-us-breakthrough-therapy-designation/412790378
- Published: 2019-08-14T07:17:12+01:00
- Author: Amilia Stone

**[AstraZeneca plc](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l)**(
[LON:AZN](https://www.directorstalkinterviews.com/ftse-company/astrazeneca/azn.l))
today announced that the US Food and Drug Administration has granted Breakthrough
Therapy Designation for _Calquence_ as a monotherapy treatment for adult patients
with chronic lymphocytic leukaemia, one of the most common types of leukaemia in
adults.^(1)

> **José Baselga, Executive Vice President, Oncology R&D, said**: “This is an important
> regulatory milestone for our work in haematology and for patients living with 
> chronic lymphocytic leukaemia, a life-threatening disease. The Breakthrough Therapy
> Designation acknowledges the growing body of evidence that supports _Calquence_
> as a highly-selective Bruton tyrosine kinase inhibitor with the potential to offer
> patients a new, differentiated, chemotherapy-free treatment option with a favourable
> safety profile.”

The FDA granted the BTD based on positive results from the interim analyses of the
ELEVATE-TN and ASCEND Phase III clinical trials. Together the trials showed that
_Calquence_ alone or in combination significantly increased the time patients lived
without disease progression or death, with safety and tolerability that was consistent
with its established profile.

This is the 10th BTD that AstraZeneca has received from the FDA since 2014. An FDA
BTD is designed to accelerate the development and regulatory review of new medicines
that are intended to treat a serious condition and that have shown encouraging early
clinical results which may demonstrate substantial improvement on a clinically-significant
endpoint over currently-available medicines.

_Calquence_ is currently approved for the treatment of adults with relapsed or refractory
mantle cell lymphoma (MCL) in the US, Brazil, Qatar, the United Arab Emirates, Mexico,
Argentina and recently Singapore and is being developed for the treatment of CLL
and other blood cancers. The positive results from both the ELEVATE-TN and ASCEND
trials will serve as the foundation for regulatory submissions later this year.

**About 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
vs. 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
or unacceptable toxicity) in combination with obinutuzumab. Patients in the third
arm received _Calquence_ monotherapy (100mg twice daily until disease progression
or unacceptable toxicity).^(2)

The primary endpoint is progression-free survival (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.^(2)

**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.^(
2) 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 physician’s choice
of either rituximab in combination with idelalisib or rituximab in combination with
bendamustine.^(3,4)

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.^(3,4)

**About **_**Calquence**_

_Calquence_ (acalabrutinib) was granted accelerated approval by the US FDA in October
2017 for the treatment of adult patients with MCL who have received at least one
prior therapy. Continued approval for this indication may be contingent upon verification
and description of clinical benefit in confirmatory trials.

_Calquence_ is an inhibitor of Bruton tyrosine kinase (BTK). _Calquence_ binds covalently
to BTK, thereby inhibiting its activity.^(5) In beta (B) cells, BTK signalling results
in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis,
and adhesion.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma
are currently evaluating _Calquence_ in 26 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, follicular
lymphoma, and multiple myeloma and other haematologic malignancies. Several Phase
III clinical trials in CLL are ongoing, including ASCEND, ELEVATE-TN, ELEVATE-RR(
ACE-CL-006) evaluating acalabrutinib vs. ibrutinib in patients with previously-treated
high-risk CLL, and ACE-CL-311 evaluating acalabrutinib in combination with venetoclax
and with/without obinutuzumab in patients with previously-untreated CLL without 
17p deletion or TP53 mutation.

**About chronic lymphocytic leukaemia**

Chronic lymphocytic leukaemia (CLL) is one of the most common type of leukaemia 
in adults, with an estimated 105,000 new cases globally and 20,720 new cases in 
the US annually, and prevalence that is expected to grow with improved treatment.
^(1,6,7,8) In CLL, too many blood stem cells in the bone marrow become abnormal 
lymphocytes and these abnormal cells have difficulty fighting infections.^(1) As
the number of abnormal cells grows there is less room for healthy white blood cells,
red blood cells and platelets.^(1)This could result in anaemia, infection and bleeding.
^(1) 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.

In October 2018, AstraZeneca and Innate Pharma announced a global strategic collaboration
that included Innate Pharma licensing the US commercial rights of _Lumoxiti_ (moxetumomab
pasudotox-tdfk), and with support from AstraZeneca, will continue EU development
and commercialisation, pending regulatory submission and approval.

**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 
investment 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.

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