CALQUENCE® (acalabrutinib) Granted US Breakthrough Therapy Designation for Chronic Lymphocytic Leukemia

Designation based on positive results from two Phase III trials

WILMINGTON, DE, USA I August 14, 2019 I AstraZeneca today announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for CALQUENCE® (acalabrutinib) as a monotherapy treatment for adult patients with chronic lymphocytic leukemia (CLL), one of the most common types of leukemia in adults.

José Baselga, Executive Vice President, Oncology R&D, said: “This is an important regulatory milestone for our work in hematology and for patients living with chronic lymphocytic leukemia, 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 favorable 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 with obinutuzumab, 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. In the US, this 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. 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 randomized, multicenter, 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 randomized (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).

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.

About ASCEND

ASCEND (ACE-CL-309) is a global, randomized, multicenter, open-label Phase III trial evaluating the efficacy of CALQUENCE in previously-treated patients with CLL. In the trial, 310 patients were randomized (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 in combination with idelalisib or rituximab in combination with bendamustine.

The primary endpoint is PFS assessed by an IRC, and key secondary endpoints include investigator-assessed PFS, IRC- and investigator-assessed overall response rate and duration of response, as well as overall survival, patient reported outcomes and time to next treatment.

About CALQUENCE

CALQUENCE® (acalabrutinib) was granted accelerated approval by the US Food and Drug Administration (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. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.

As part of an extensive clinical development program, 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, Waldenstrom macroglobulinemia, follicular lymphoma, and multiple myeloma and other hematologic malignancies. Several Phase III clinical trials 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 leukemia (CLL)

Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults, with an estimated 191,000 new cases globally and 20,720 new cases in the US annually, and prevalence that is expected to grow with improved treatment. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows there is less room for healthy white blood cells, red blood cells and platelets. This could result in anemia, infection and bleeding. B-cell receptor signaling through BTK is one of the essential growth pathways for CLL.

About AstraZeneca in hematology

Leveraging its strength in oncology, AstraZeneca has established hematology as one of four key oncology disease areas of focus. The Company’s hematology franchise includes two US FDA-approved medicines and a robust global development program for a broad portfolio of potential blood cancer treatments. Acerta Pharma serves as AstraZeneca’s hematology 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 commercialization, 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, we are committed to advance Oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to our core capabilities, we actively pursue innovative partnerships and investments that accelerate the delivery of our strategy as illustrated by our investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumor Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalized 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 commercialization of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism and Respiratory. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

SOURCE: AstraZeneca

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