New Long-Term Data on CALQUENCE Presented at ASH 2018 | Financial Buzz

New Long-Term Data on CALQUENCE Presented at ASH 2018

AstraZeneca and Acerta Pharma, its hematology research and development
center of excellence, have presented new, long-term follow-up results
for CALQUENCE® (acalabrutinib) in patients with relapsed or
refractory mantle cell lymphoma (MCL) and updated results of an ongoing
clinical trial assessing acalabrutinib monotherapy in treatment-naïve
patients with chronic lymphocytic leukemia (CLL) at the 60th
American Society of Hematology (ASH) Annual Meeting & Exposition in San
Diego, CA.

Sean Bohen, Executive Vice President, Global Medicines Development and
Chief Medical Officer, said: “The data from these two clinical trials
validate previous findings and add to the growing body of evidence that
support the promise of CALQUENCE in multiple blood cancers. We are very
encouraged by these results, which reinforce our commitment to advancing
innovative treatments for blood cancer patients.”

CALQUENCE follow-up data in MCL confirms efficacy and tolerability

Long-term follow-up data presented from the Phase II ACE-LY-004
trial in relapsed or refractory MCL showed sustained and clinically
meaningful responses to CALQUENCE with a median follow-up of more than
two years (26 months), confirming its efficacy and safety profile in
this patient population. Initial
data from this trial served as the basis for the accelerated
approval of CALQUENCE for the treatment of adult patients with MCL
who have received at least one prior therapy by the US Food and Drug
Administration (FDA) in October 2017.

Michael L. Wang, MD, Professor, Department of Lymphoma/Myeloma, The
University of Texas MD Anderson Cancer Center, and Principal
Investigator of the ACE-LY-004 MCL trial, said: “It’s encouraging to see
the sustained duration of response in the updated analysis and the
safety profile of acalabrutinib maintained consistently over time in MCL
patients. As we gain more and more experience with this therapy, its
importance as a treatment option for relapsed or refractory MCL is being
more fully realized across the clinical and patient community.”

Summary of key investigator-assesseda efficacy results from
the open-label, single-arm clinical trial of CALQUENCE in 124 adult
patients with relapsed or refractory MCL:

Overall response rate(Complete response + partial response)

a Response was assessed based on the Lugano classification.b
Confidence interval (CI).c Includes patients without
any adequate post-baseline disease assessment.

The median follow-up was 26 months, with 40% of patients remaining on
treatment with CALQUENCE at the time of analysis. An exploratory
analysis of the trial found that an undetectable minimal residual
disease status was achieved in a sub-set of patients.

In this trial, the most frequent adverse events (AEs ? 20%, all grades)
were headache (38%), diarrhea (36%), fatigue (28%), cough (22%) and
myalgia (21%). These events were primarily Grade 1/2. Grade 3/4 AEs
(reported ? 5%) were anemia (11%), neutropenia (11%) and pneumonia (6%).
There were 13 patients (10%) with 16 cardiac events including four Grade
3/4 events, each in one patient (acute coronary syndrome, acute
myocardial infarction, cardiorespiratory arrest, coronary artery
disease). There was no new onset of atrial fibrillation. Bleeding events
occurred in 33% of patients, most frequently contusion (13%) and
petechiae (9%); and all bleeding events but three (2%, Grade 3) were
Grade 1/2 events. Ten patients discontinued treatment due to AEs. In
total there were six deaths due to AEs (none of which were considered to
be related to CALQUENCE).

New data from ongoing CLL clinical trial demonstrate strong efficacy

Updated results of the Phase I/II ACE-CL-001
trial were presented today in an oral session. In a cohort of
treatment-naïve patients with CLL, a long-term safety and efficacy
assessment showed high response rates with no new safety signals
identified. The median time on trial was 42 months, with 89% of patients
remaining on treatment with acalabrutinib at the time of analysis.

John C. Byrd, MD, Distinguished University Professor, The Ohio State
University, and Principal Investigator for the ACE-CL-001 CLL clinical
trial, said: “A key challenge in the treatment of CLL is ensuring
patients have therapies that they can tolerate and benefit from over the
long term. The results seen in this patient cohort at 3.5 years of
follow-up are encouraging for both durability of response and
tolerability of therapy. We look forward to continued data from ongoing
studies evaluating acalabrutinib in CLL.”

Summary of key investigator-assesseda efficacy results from
the Phase I/II open-label, single-arm ACE-CL-001 acalabrutinib trial in
99 patients with CLL, evaluating the treatment-naïve cohort:

Overall response rate(Complete response + partial response)

a Response was assessed using International Workshop on
Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria with modification for
lymphocytosis.b Only responders with ? partial response
were included in this analysis.c Not reached (NR).d
Confidence interval (CI).e Based on the Kaplan-Meier
estimates.

In this trial, the most common AEs (? 20%, all grades) were diarrhea
(49%), headache (44%), upper respiratory tract infection (40%),
contusion (39%), arthralgia (33%), weight increased (31%), nausea (30%)
and cough (23%). Grade 3/4 AEs (reported ? 5%) were neutropenia (8%),
hypertension (7%), diarrhea (5%) and headache (5%). Atrial fibrillation
and hypertension (all grades) occurred in 6% and 17% of patients,
respectively, with Grade 3 events occurring in 2% and 7% of patients.
Bleeding events (all grades) occurred in 64% of patients with contusion
being most common (39%). All but three (3% Grade 3) bleeding events were
Grade 1/2 events and no patients discontinued due to bleeding. Overall,
11% of patients discontinued treatment, 5% of which were due to AEs,
including secondary malignancies (angiosarcoma, glioblastoma multiforme,
small cell lung cancer), sepsis (Grade 4) and urinary tract infection
(Grade 3). One Grade 5 event (multiorgan failure) in the setting of
pneumonia was reported, which was considered unrelated to acalabrutinib.

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE (acalabrutinib)

Hemorrhage

Serious hemorrhagic events, including fatal events, have occurred in the
combined safety database of 612 patients with hematologic malignancies
treated with CALQUENCE monotherapy. Grade 3 or higher bleeding events,
including gastrointestinal, intracranial, and epistaxis, have been
reported in 2% of patients. Overall, bleeding events, including bruising
and petechiae of any grade, occurred in approximately 50% of patients
with hematological malignancies.

The mechanism for the bleeding events is not well understood.

CALQUENCE may further increase the risk of hemorrhage in patients
receiving antiplatelet or anticoagulant therapies, and patients should
be monitored for signs of bleeding.

Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre-
and post-surgery, depending upon the type of surgery and the risk of
bleeding.

Infection

Serious infections (bacterial, viral, or fungal), including fatal events
and opportunistic infections, have occurred in the combined safety
database of 612 patients with hematologic malignancies treated with
CALQUENCE monotherapy. Grade 3 or higher infections occurred in 18% of
these patients. The most frequently reported Grade 3 or 4 infection was
pneumonia. Infections due to hepatitis B virus (HBV) reactivation and
progressive multifocal leukoencephalopathy (PML) have occurred.

Monitor patients for signs and symptoms of infection and treat as
medically appropriate. Consider prophylaxis in patients who are at
increased risk for opportunistic infections.

Cytopenias

In the combined safety database of 612 patients with hematologic
malignancies, patients treated with CALQUENCE monotherapy experienced
Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (11%), and
thrombocytopenia (8%), based on laboratory measurements. Monitor
complete blood counts monthly during treatment.

Second Primary Malignancies

Second primary malignancies, including non-skin carcinomas, have
occurred in 11% of patients with hematologic malignancies treated with
CALQUENCE monotherapy in the combined safety database of 612 patients.
The most frequent second primary malignancy was skin cancer, reported in
7% of patients. Advise protection from sun exposure.

Atrial Fibrillation and Flutter

In the combined safety database of 612 patients with hematologic
malignancies treated with CALQUENCE monotherapy, atrial fibrillation and
atrial flutter of any grade occurred in 3% of patients, and Grade 3 in
1% of patients. Monitor for atrial fibrillation and atrial flutter and
manage as appropriate.

ADVERSE REACTIONS

The most common adverse reactions (?20%) of any grade were anemia,*
thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue
(28%), myalgia (21%), and bruising (21%).

*Treatment-emergent decreases (all grades) of hemoglobin (46%),
platelets (44%), and neutrophils (36%) were based on laboratory
measurements and adverse reactions.

The most common Grade ? 3 non-hematological adverse reaction (reported
in at least 2% of patients) was diarrhea (3.2%).

Dosage reductions or discontinuations due to any adverse reaction were
reported in 1.6% and 6.5% of patients, respectively.

Increases in creatinine 1.5 to 3 times the upper limit of normal
occurred in 4.8% of patients.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration with a
strong CYP3A inhibitor. If a strong CYP3A inhibitor will be used
short-term, interrupt CALQUENCE.

Moderate CYP3A Inhibitors: When CALQUENCE is co-administered
with a moderate CYP3A inhibitor, reduce CALQUENCE dose to 100 mg once
daily.

Strong CYP3A Inducers: Avoid co-administration with a strong
CYP3A inducer. If a strong CYP3A inducer cannot be avoided, increase the
CALQUENCE dose to 200 mg twice daily.

Gastric Acid Reducing Agents: If treatment with a gastric
acid reducing agent is required, consider using an H2-receptor
antagonist or an antacid. Take CALQUENCE 2 hours before taking an
H2-receptor antagonist. Separate dosing with an antacid by at least 2
hours.

Avoid co-administration with proton pump inhibitors. Due to the
long-lasting effect of proton pump inhibitors, separation of doses may
not eliminate the interaction with CALQUENCE.

SPECIFIC POPULATIONS

There is insufficient clinical data on CALQUENCE use in pregnant women
to inform a drug-associated risk for major birth defects and
miscarriage. Advise women of the potential risk to a fetus.

It is not known if CALQUENCE is present in human milk. Advise lactating
women not to breastfeed while taking CALQUENCE and for at least 2 weeks
after the final dose.

Please see complete Prescribing
Information including Patient Information.

NOTES TO EDITORS

About CALQUENCE (acalabrutinib)

CALQUENCE® (acalabrutinib) 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.

CALQUENCE was granted accelerated approval by the US Food and Drug
Administration (FDA) in October 2017 for the treatment of adult patients
with mantle cell lymphoma (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 not currently licensed for the treatment of chronic
lymphocytic leukemia (CLL).

Acalabrutinib was granted Orphan Drug Designation for the treatment of
patients with CLL, MCL and Waldenström macroglobulinemia in 2015, and
Breakthrough Therapy Designation in August 2017 by the US FDA for the
treatment of patients with MCL who have received at least one prior
therapy.

About Mantle Cell Lymphoma (MCL)

MCL is a rare type of B-cell non-Hodgkin lymphoma (NHL). MCL accounts
for approximately 3% of new NHL cases in the US, with approximately
3,300 new cases of MCL diagnosed in the US each year. The median age at
diagnosis is 68 years, with MCL occurring more than twice as often in
men than women. While MCL patients initially respond to
treatment, there is a high relapse rate.

About Chronic Lymphocytic Leukemia (CLL)

CLL is the most common type of leukemia in adults and accounts for
approximately one in four cases of leukemia. The average age at the time
of diagnosis is approximately 70 years of age. 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 center of excellence. 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 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 Acerta Pharma

Acerta Pharma, a member of the AstraZeneca Group, is creating novel
therapies intended for the treatment of cancer and autoimmune diseases.
AstraZeneca acquired a majority stake interest in Acerta Pharma, which
serves as AstraZeneca’s hematology research and development center of
excellence. For more information, please visit www.acerta-pharma.com.

About MedImmune

MedImmune is the global biologics research and development arm of
AstraZeneca, a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialization of small
molecule and biologic prescription medicines. MedImmune is pioneering
innovative research and exploring novel pathways across Oncology,
Respiratory, Cardiovascular, Renal and Metabolic Diseases, and Infection
and Vaccines. The MedImmune headquarters is located in Gaithersburg, MD,
one of AstraZeneca’s three global R&D centers, with additional sites in
Cambridge, UK and South San Francisco, CA. For more information, please
visit www.medimmune.com.

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.

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