AstraZeneca advances scientific leadership in hematology at ASH 2023

CALQUENCE six-year follow-up data reinforce long-term benefit in chronic lymphocytic leukemia, and data across multiple hematology assets showcase breadth of promising early pipeline

New, longer-term data from ALPHA Phase III trial will further show potential of danicopan to address clinically significant extravascular hemolysis and maintain disease control, allowing paroxysmal nocturnal hemoglobinuria patients to continue standard-of-care treatment with ULTOMIRIS or SOLIRIS

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca will present new clinical and real-world data in multiple hematological conditions at the 65th American Society of Hematology (ASH) Annual Meeting andExposition, December 9 to 12, 2023 in San Diego, CA.

A total of 63 abstracts will feature 14 approved and potential new medicines across the Company’s portfolio and pipeline including from Alexion, AstraZeneca’s Rare Disease group, in chronic lymphocytic leukemia (CLL) and several types of lymphoma, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS) and amyloid light-chain (AL) amyloidosis.

Anas Younes, Senior Vice President, Hematology R&D, AstraZeneca, said: “Our data at ASH will exemplify how we are advancing a range of innovative modalities including antibody drug conjugates, next-generation immunotherapies and T-cell engagers in hematology. Updated clinical data for AZD0486, our CD19/CD3 T-cell engager, reinforce our belief in this approach as a potential new treatment for lymphoma, and new CALQUENCE data continue to demonstrate long-term efficacy and safety in chronic lymphocytic leukemia with further follow up.”

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, said: “Alexion has transformed the treatment landscape and redefined care for the paroxysmal nocturnal hemoglobinuria patient community over the past two decades. At the ASH Annual Meeting, new results from our pivotal ALPHA trial will demonstrate the promise of Factor D inhibition to advance care for the small subset of patients with paroxysmal nocturnal hemoglobinuria who experience clinically significant extravascular hemolysis. We are proud to further our leadership in rare disease by sharing data from our robust hematology pipeline, reflecting our commitment to innovation and improving outcomes for the patients and families we serve.”

CALQUENCE^® (acalabrutinib) continues to demonstrate long-term benefits in CLL

Six-year follow-up data from the pivotal ELEVATE-TN Phase III trial will further support the continued efficacy, safety and tolerability of CALQUENCE for long-term use in patients with treatment-naïve CLL.¹

Data from a Phase II trial will show the safety and efficacy of CALQUENCE and rituximab followed by chemotherapy and autologous stem cell transplantation in fit patients with treatment-naïve mantle cell lymphoma (MCL).²

An analysis of five prospective CALQUENCE trials, including three randomized, controlled Phase III trials and two non-randomized trials, will show acceptable safety outcomes based on rates of nonfatal and fatal ventricular arrhythmias and sudden death in patients with CLL.³

Novel early assets show potential to improve outcomes for blood cancer patients

Data from our early portfolio will demonstrate how the Company is advancing multiple modalities across several scientific platforms, including Immuno-Oncology, Immune-Engagers, Antibody Drug Conjugates (ADCs) and Epigenetics as part of its strategy to attack cancer from multiple angles.

Updated Phase I data for AstraZeneca’s CD19/CD3 T-cell engager, AZD0486, will further demonstrate the acceptable safety profile and high response rate of this treatment in relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL).⁴ We will also present the first clinical data on sabestomig, a PD-1/TIM-3 targeting bispecific antibody, in R/R Hodgkin lymphoma, showing encouraging early signals of activity.⁵

The first preclinical data for AZD9829, a novel CD123-targeting ADC, using AstraZeneca’s proprietary linker technology to deliver a topoisomerase I inhibitor warhead, will demonstrate promising anti-tumor activity in acute myeloid leukemia.⁶ In addition, preclinical data will demonstrate anti-tumor activity of AstraZeneca’s novel PRMT5 inhibitor in MTAP silenced Hodgkin lymphoma models.⁷

Showcasing advances to bolster our leadership in PNH with new data on Factor D inhibition and impact of C5 inhibition in long-term disease control

New results from the 24-week and long-term extension period from the pivotal ALPHA Phase III trial will reinforce the potential for danicopan add-on therapy to address clinically significant extravascular hemolysis (EVH) in the small subset of PNH patients who experience this condition while treated with C5 inhibitor therapy, allowing them to maintain control of intravascular hemolysis (IVH) through standard-of-care treatment with ULTOMIRIS^® (ravulizumab-cwvz) or SOLIRIS^® (eculizumab).⁸

Further, patient-reported outcomes from the ALPHA trial will suggest danicopan as an add-on to ULTOMIRIS or SOLIRIS improved quality of life compared to C5 inhibitor therapy alone in patients with PNH who experience clinically significant EVH.⁹

Additionally, Alexion will present an analysis of six-year outcomes from the Phase III clinical trial evaluating the safety and efficacy of ULTOMIRIS in patients with PNH who did not have previous treatment with a C5 inhibitor.¹⁰ The analysis compared survival against untreated patients in the International PNH Registry, the largest global real-world database of patients with PNH. Results will suggest ULTOMIRIS improved survival and maintained effective long-term control of IVH, the most significant contributor to morbidity and premature mortality in PNH.¹⁰

Improving diagnosis and management of life-threatening rare diseases, including amyloidosis

24-month results of a Phase II trial will demonstrate the safety and tolerability of CAEL-101 in combination with cyclophosphamide-bortezomib-dexamethasone with or without daratumumab for the treatment of AL amyloidosis.¹¹

Real-world analyses across AL amyloidosis, aHUS and hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will also be presented, advancing the scientific understanding of these rare, hematological conditions.^12-16

Key presentations during the 65th ASH Annual Meeting and Exposition

INDICATIONS AND USAGE

CALQUENCE is a Bruton tyrosine kinase (BTK) inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

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.

CALQUENCE is also indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

IMPORTANT SAFETY INFORMATION ABOUT CALQUENCE^® (acalabrutinib) tablets

Serious and Opportunistic Infections

Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE.

Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (11% of all patients, including pneumonia in 6%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly.

Hemorrhage

Fatal and serious hemorrhagic events have occurred in patients with hematologic malignancies treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patients.

Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 2.7% of patients taking CALQUENCE without antithrombotic agents and 3.6% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding.

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

Cytopenias

Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients with hematologic malignancies treated with CALQUENCE. Grade 4 neutropenia developed in 12% of patients. Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted.

Second Primary Malignancies

Second primary malignancies, including skin cancers and other solid tumors, occurred in 12% of 1029 patients exposed to CALQUENCE in clinical trials. The most frequent second primary malignancy was skin cancer, reported in 6% of patients. Monitor patients for skin cancers and advise protection from sun exposure.

Atrial Fibrillation and Flutter

Grade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (eg, palpitations, dizziness, syncope, dyspnea) and manage as appropriate.

ADVERSE REACTIONS

The most common adverse reactions (≥20%) of any grade in patients with relapsed or refractory MCL were anemia,* thrombocytopenia,* headache (39%), neutropenia,* diarrhea (31%), fatigue (28%), myalgia (21%), and bruising (21%). The most common Grade ≥3 non-hematological adverse reaction (reported in at least 2% of patients) was diarrhea (3.2%).

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

Dose reductions or discontinuations due to any adverse reaction were reported in 1.6% and 6.5% of patients, respectively. Increases in creatinine to 1.5 to 3 times the upper limit of normal (ULN) occurred in 4.8% of patients.

The most common adverse reactions (≥30%) of any grade in patients with CLL were anemia,* neutropenia,* thrombocytopenia,* headache, upper respiratory tract infection, and diarrhea.

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

In patients with previously untreated CLL exposed to CALQUENCE, fatal adverse reactions that occurred in the absence of disease progression and with onset within 30 days of the last study treatment were reported in 2% for each treatment arm, most often from infection. Serious adverse reactions were reported in 39% of patients in the CALQUENCE plus obinutuzumab arm and 32% in the CALQUENCE monotherapy arm, most often due to events of pneumonia (7% and 2.8%, respectively).

Adverse reactions led to CALQUENCE dose reduction in 7% and 4% of patients in the CALQUENCE plus obinutuzumab arm (N=178) and CALQUENCE monotherapy arm (N=179), respectively. Adverse events led to discontinuation in 11% and 10% of patients, respectively. Increases in creatinine to 1.5 to 3 times ULN occurred in 3.9% and 2.8% of patients in the CALQUENCE combination arm and monotherapy arm, respectively.

In patients with relapsed/refractory CLL exposed to CALQUENCE, serious adverse reactions occurred in 29% of patients. Serious adverse reactions in >5% of patients who received CALQUENCE included lower respiratory tract infection (6%). Fatal adverse reactions within 30 days of the last dose of CALQUENCE occurred in 2.6% of patients, including from second primary malignancies and infection.

Adverse reactions led to CALQUENCE dose reduction in 3.9% of patients (N=154), dose interruptions in 34% of patients, most often due to respiratory tract infections followed by neutropenia, and discontinuation in 10% of patients, most frequently due to second primary malignancies followed by infection. Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% of patients who received CALQUENCE.

DRUG INTERACTIONS

Strong CYP3A Inhibitors: Avoid co-administration of CALQUENCE with a strong CYP3A inhibitor. If these inhibitors will be used short-term, interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE.

Moderate CYP3A Inhibitors: Reduce the dosage of CALQUENCE to 100 mg once daily when co-administered with a moderate CYP3A inhibitor.

Strong CYP3A Inducers: Avoid co-administration of CALQUENCE with a strong CYP3A inducer. If co-administration is unavoidable, increase the dosage of CALQUENCE to 200 mg approximately every 12 hours.

SPECIFIC POPULATIONS

Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. Advise pregnant women of the potential risk to a fetus.

Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy.

Contacts

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+1 302 885 2677

Miranda Kulp

+1 302 885 2677

US Media Mailbox: usmediateam@astrazeneca.com

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