Calquence six-year follow-up data reinforce long-term benefit in chronic lymphocytic leukaemia, and data across multiple haematology 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 haemolysis and maintain disease control, allowing paroxysmal nocturnal haemoglobinuria patients to continue standard-of-care treatment with Ultomiris or Soliris.

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

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 leukaemia (CLL) and several types of lymphoma, paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS) and amyloid light-chain (AL) amyloidosis.

Anas Younes, Senior Vice President, Haematology 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 haematology. 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 leukaemia 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 haemoglobinuria 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 haemoglobinuria who experience clinically significant extravascular haemolysis. We are proud to further our leadership in rare disease by sharing data from our robust haematology pipeline, reflecting our commitment to innovation and improving outcomes for the patients and families we serve.”

Calquence 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 randomised, controlled Phase III trials and two non-randomised 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-tumour activity in acute myeloid leukaemia.⁶ In addition, preclinical data will demonstrate anti-tumour 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 haemolysis (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 haemolysis (IVH) through standard-of-care treatment with Ultomiris (ravulizumab) 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 haematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA) will also be presented, advancing the scientific understanding of these rare, haematological conditions.^12-16

Key presentations during the 65th ASH Annual Meeting and Exposition

Notes

AstraZeneca in haematology
AstraZeneca is pushing the boundaries of science to redefine care in haematology. We have expanded our commitment to patients with haematologic conditions, not only in oncology but also in rare diseases with the acquisition of Alexion, allowing us to reach more patients with high unmet needs. By applying our deep understanding of blood cancers, leveraging our strength in solid tumour oncology and delivering on Alexion’s pioneering legacy in complement science to provide innovative medicines for rare diseases, we are pursuing the end-to-end development of novel therapies designed to target underlying drivers of disease.

By targeting haematologic conditions with high unmet medical needs, we aim to deliver innovative medicines and approaches to improve patient outcomes. Our goal is to help transform the lives of patients living with malignant, rare and other related haematologic diseases, shaped by insights from patients, caregivers and physicians to have the most meaningful impact.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

Alexion
Alexion, AstraZeneca Rare Disease, is the group within AstraZeneca focused on rare diseases, created following the 2021 acquisition of Alexion Pharmaceuticals, Inc. As a leader in rare diseases for more than 30 years, Alexion is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and commercialisation of life-changing medicines. Alexion focuses its research efforts on novel molecules and targets in the complement cascade and its development efforts on haematology, nephrology, neurology, metabolic disorders, cardiology and ophthalmology. Headquartered in Boston, Massachusetts, Alexion has offices around the globe and serves patients in more than 50 countries.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, 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 social media @AstraZeneca.

Contacts
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References

1. Sharman JP, Egyed M, Jurczak J, et al. Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-naive Chronic Lymphocytic Leukemia: 6-year Follow-up of ELEVATE-TN. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 636.
2. Hawkes EA, Lee ST, Churilov L, et al. A Window Study of Acalabrutinib, Rituximab, Followed by Chemotherapy and Autograft (ASCT) in Fit Patients with Treatment-naïve Mantle Cell Lymphoma (MCL): The Investigator-led Australasian Leukaemia and Lymphoma Group NHL33 ‘WAMM’ Trial. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 735.
3. Sharman JP, Ghia P, Miranda P, et al. Analysis of Ventricular Arrhythmias and Sudden Death with Acalabrutinib From 5 Prospective Clinical Trials. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 4643.
4. Gaballa S, Nair R, Jacobs R, et al. Double step-up dosing (2SUD) Regimen Mitigates Severe ICANS and CRS While Maintaining High Efficacy in Subjects with Relapsed/Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) Treated with AZD0486, a Novel CD19xCD3 T-cell Engager (TCE): Updated Safety and Efficacy data from the Ongoing First-in-human (FIH) Phase 1 trial. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 1662.
5. Mei M, Corazzelli G, Morschhauser F, et al. Safety and Preliminary Efficacy of Sabestomig (AZD7789), an Anti-PD-1 and Anti-TIM-3 Bispecific Antibody, in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma Previously Treated with Anti-PD-(L)1 Therapy. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 4433.
6. Dutta D, Pan P, Fleming R, et al. First Disclosure of AZD9829, a TOP1i-ADC Targeting CD123: Promising Preclinical Activity in AML Models with Minimal Effect on Healthy Progenitors. Presented at American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. e-Publication.
7. Urosevic J, Lynch JT, Meyer S, et al. Epigenetic Silencing of MTAP in Hodgkin’s Lymphoma Renders it Sensitive to a 2nd Generation PRMT5 Inhibitor. Presented at: American Society of Hematology (ASH) Annual Meeting and Exposition 2023; 9-12 December 2023; San Diego, California. Abs 4185.
8. Kulasekararaj A, Griffin M, Piatek CI, et al. Danicopan as Add-on Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis: Phase 3 Long-term Data. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA. Abs 576.
9. Piatek C, Lee JW, Griffin M, et al. Patient-Reported Outcomes: Danicopan as Add-On Therapy to Ravulizumab or Eculizumab Versus Placebo in Patients with Paroxysmal Nocturnal Hemoglobinuria and Clinically Significant Extravascular Hemolysis. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA. Abs 1346.
10. Kulasekararaj A, Schrezenmeier H, Usuki K, et al. Ravulizumab Provides Durable Control of Intravascular Hemolysis and Improves Survival in Patients with Paroxysmal Nocturnal Hemoglobinuria: Long-term Follow-up of Study 301 and Comparisons with Patients of the International PNH Registry. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA. Abs 2714.
11. Valent J, Liedtke M, Zonder JA, et al. Safety and Tolerability of CAEL-101, an Anti-Amyloid Monoclonal Antibody, Combined with Anti-Plasma Cell Dyscrasia Therapy in Patients with Light-Chain Amyloidosis: 24-Month Results of a Phase 2 Study. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA. Abs 540.
12. Lyons G, et al. Treatment Patterns and Outcomes for Patients with Light Chain (AL) Amyloidosis: Analysis of a Large US Claims Database. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA.
13. Thompson J, et al. Real-world Treatment Patterns Following Update to National Comprehensive Cancer Network Guidelines for Light-Chain Amyloidosis: Results from a US Administrative Claims Database. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA.
14. Laires P, et al. Prevalence, Incidence, and Characterization of Light Chain Amyloidosis in the USA: A Real-world Analysis Utilizing Electronic Health Records (EHR). Presented at: American Society of Hematology (ASH) Congress; 9-12 December, 2023; San Diego, CA.
15. Wang Y, et al. Patient Characteristics and Diagnostic Journey of Thrombotic Microangiopathy Associated with a Trigger: A Real-world, Retrospective, Multi-National Study. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA.
16. Wang Y, Rava A, Smuzynski M, et al. Real-world Analysis of the Underdiagnosis, Clinical Outcomes and Associated Burden of Hematopoietic Stem Cell Transplantation-associated Thrombotic Microangiopathy (HSCT-TMA) in the United States of America. Presented at: American Society of Hematology (ASH) Congress; 9-12 December 2023; San Diego, CA. Abs 491.