AstraZeneca showcases scientific advances across rare and malignant haematological conditions at EHA 2023

Pivotal ALPHA Phase III trial results will show benefit of danicopan, Alexion's first-in-class Factor D inhibitor, in improving clinically significant extravascular haemolysis while allowing patients with PNH to remain on standard of care treatment.
Calquence data will reinforce role as a preferred treatment option for chronic lymphocytic leukaemia and mantle cell lymphoma.
Interim clinical data will show promise of AZD0486, a novel T-cell engager for patients with relapsed or refractory follicular lymphoma.

AstraZeneca will present new clinical and real-world data in multiple haematological conditions, further demonstrating its ambition to redefine care in haematology at the European Hematology Association (EHA) 2023 Hybrid Congress, 8 to 11 June 2023.

A total of 29 abstracts will feature 10 approved and potential new medicines across the Company’s haematology portfolio and pipeline spanning more than 10 types of haematological conditions and rare diseases.

This includes a presentation from Alexion, AstraZeneca’s Rare Disease group, reporting positive results from the pivotal ALPHA Phase III trial evaluating the investigational first-in-class oral Factor D inhibitor danicopan (ALXN2040) as an add-on to standard of care C5 inhibitor therapy Ultomiris (ravulizumab) or Soliris (eculizumab).¹ Data show add-on treatment with danicopan significantly improved signs and symptoms of clinically significant extravascular haemolysis (EVH) in the small subset of patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with C5 inhibition who are affected, allowing them to maintain treatment with standard of care and disease control.¹ PNH is a rare and severe blood disorder characterised by the destruction of red blood cells, known as intravascular haemolysis (IVH), and white blood cell and platelet activation that can cause thrombosis (blood clots) and result in organ damage and potentially premature death.^2-4

Gianluca Pirozzi, Senior Vice President, Head of Development, Regulatory and Safety, Alexion, said: “We look forward to presenting results at EHA from the ALPHA Phase III trial showing the potential for danicopan, as an add-on to Ultomiris or Soliris, to address clinically significant EVH, which can impact approximately 10% to 20% of PNH patients treated with C5 inhibitors, while allowing them to maintain treatment with standard of care. Additional presentations will highlight our momentum in expanding our pipeline beyond complement to address the needs of more people living with rare diseases.”

Additionally, AstraZeneca will present new data analyses, external collaborations and real-world data that will continue to display the long-term safety and efficacy of Calquence (acalabrutinib) in patients with chronic lymphocytic leukaemia (CLL), including a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of Calquence versus zanubrutinib in relapsed or refractory CLL, demonstrating Calquence’s meaningfully differentiated profile.⁵ New tolerability and efficacy data showing the activity of Calquence in combination with bendamustine and rituximab for the treatment of mantle cell lymphoma
(MCL) will also be presented.⁶

The Company will present data on AZD0486, a CD19/CD3 next-generation T-cell engager for patients with relapsed or refractory follicular lymphoma (FL).⁷ New clinical data demonstrating the emerging potential of capivasertib, an AKT inhibitor, in the treatment of relapsed or refractory non-Hodgkin lymphoma (NHL), and AZD4573, a CDK9 inhibitor, in the treatment of peripheral T-cell lymphoma (PTCL) will also be presented.^8,9

Anas Younes, Senior Vice President, Haematology R&D, AstraZeneca, said: “Our data at EHA will showcase the promise of our growing haematology pipeline, reinforcing our dedication to patients with haematologic conditions. We are excited to share new Calquence analyses that will further build on our medicine’s differentiated long-term efficacy and safety profile in chronic lymphocytic leukaemia and mantle cell lymphoma. Positive clinical data on our CD19/CD3 T-cell engager and our oral AKT inhibitor, capivasertib, will showcase their potential as treatments for patients with lymphoma.”

Advancing the treatment landscape to improve outcomes for more patients with PNH

• A prespecified interim efficacy analysis from the ALPHA Phase III trial of danicopan as an add-on to Ultomiris or Soliris will show its potential to improve haemoglobin levels and reduce the need for transfusions in the small subset of people living with PNH who experience clinically significant EVH, while on standard of care.¹
• Real-world and clinical trial data will estimate that the prevalence of clinically significant EVH in patients with PNH who are receiving C5 inhibitor therapy ranges from 7% to 21%. Additionally, the data will offer insights into disease control and treatment satisfaction among patients and physicians.¹⁰
• An analysis of outcomes up to four years from the pivotal, Phase III trial and open-label extension of Ultomiris in C5 inhibitor-experienced adults with PNH will further support its long-term use in PNH management. The analysis will show Ultomiris maintained effective control of intravascular haemolysis with a low incidence of major adverse vascular events and demonstrated a 98.4% survival rate throughout the four-year study period.¹¹
• An analysis of Korean registry data in patients with PNH will outline lactate dehydrogenase (LDH) levels, and not haemoglobin levels, as a predictor of thromboembolism, and thromboembolism as a predictor of death, reinforcing the importance of controlling terminal complement activation and intravascular haemolysis in the treatment of PNH.¹²

Further analyses demonstrate continued efficacy and safety for Calquence

• Data will be shared from a MAIC of the efficacy and safety of Calquence versus zanubrutinib in relapsed or refractory CLL, based on data from the ASCEND and ALPINE Phase III trials.⁵
• An interim safety analysis will display the safety and treatment adherence with Calquence in patients more than 80 years old or frail patients with CLL in an ongoing investigator-initiated Phase II trial.¹³
• A Phase Ib trial will show the safety and efficacy of Calquence, bendamustine and rituximab in patients with treatment-naïve or relapsed or refractory MCL, and support further investigation to determine if this could be an alternative treatment option for patients with MCL.⁶

Emerging pipeline molecules and treatment strategies show therapeutic potential

• Interim results for AZD0486 (TNB-486), a CD19/CD3 next-generation T-cell engager, will display a high complete response (CR) in patients with relapsed or refractory FL with a manageable safety profile in an ongoing Phase I trial.⁷
• A Phase II, open-label, multicentre trial (CAPITAL) of capivasertib, a potent, oral AKT inhibitor in patients with relapsed or refractory B-cell NHL will show the molecule had single-agent activity and a manageable safety profile in patients with heavily pretreated relapsed or refractory FL and could be a potential treatment option in NHLs more broadly.⁸
• Efficacy and safety results from a Phase IIa study looking at the CDK9 inhibitor, AZD4573, in patients with relapsed or refractory PTCL will show encouraging clinical activity as a monotherapy, including three CRs and one complete metabolic response after initial progressive disease.⁹
• Preliminary ongoing Phase I/II safety and tolerability results of AZD0466, a Bcl-2/Bcl-xl inhibitor, will show it is tolerated as a monotherapy for patients with relapsed or refractory acute leukaemia.¹⁴

Improving understanding and management of debilitating rare diseases

• Results through eighteen months on safety, tolerability and biomarker data will be presented from a Phase II trial evaluating CAEL-101, a potentially first-in-class monoclonal antibody, in adults with light-chain (AL) amyloidosis.¹⁵
• An encore presentation will highlight the design and methodology of two Phase III trials evaluating the efficacy and safety of CAEL-101 compared to placebo to reduce amyloid burden in treatment-naive patients with AL-amyloidosis with cardiac involvement.¹⁶
• Results from a double-blind survey of healthcare providers in Europe, North America and Australia will offer insight into factors influencing treatment discontinuation with C5 inhibitors for patients with atypical haemolytic uraemic syndrome (aHUS), including thrombotic microangiopathy response, haemolysis and kidney function.¹⁷

Key AstraZeneca presentations during EHA 2023

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 Twitter @AstraZeneca.

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References

1. Lee JW, Griffin M, Kim JS, et al. Patients with paroxysmal nocturnal hemoglobinuria and clinically significant extravascular hemolysis on ravulizumab/eculizumab showed hemoglobin response superiority with add-on danicopan vs placebo [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P771.
2. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014;124(18):2804-2811.
3. Griffin M, Hillmen P, Munir T, et al. Significant hemolysis is not required for thrombosis in paroxysmal nocturnal hemoglobinuria. Haematologica. 2019;104(3):e94-e96.
4. Hillmen P, et al. The Complement Inhibitor Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2006;355(12):1233-43.
5. Skarbnik A, Kittai A, Miranda M, et al. A matching adjusted indirect comparison of the efficacy and safety of acalabrutinib versus zanubrutinib in relapsed of refractory chronic lymphocytic leukemia [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P642.
6. Phillips T, Wang M, Robak T, et al. Safety and efficacy of acalabrutinib, bendamustine, and rituximab in patients with treatment-naive or relapsed/refractory mantle cell lymphoma: Phase Ib trial [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs 1094.
7. Jacobs R, Nair R, Cho SG, et al. High complete response rate with TNB-486 in relapsed/refractory follicular lymphoma: Interim results from an ongoing Phase I study [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs S224.
8. Hodson D, Shouse G, Shin H, et al. A Phase II, open-label, multicenter study of capivasertib, a potent, oral pan-AKT inhibitor, in patients with relapsed or refractory B-Cell non-hodgkin lymphoma (CAPITAL) [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P1098.
9. Shortt J, Feldman T, Collins G, et al. Encouraging complete responses (CRs) observed with CDK9 inhibitor AZD4573 in Patients (pts) with Relapsed/Refractory (r/r) Peripheral T-cell Lymphoma (PTCL): Early trial analysis [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P1141.
10. Kulasekararaj A, Mellor J, Earl L, et al. Prevalence of clinically significant extravascular hemolysis in stable C5 inhibitor-treated patients with PNH and its association with disease control, quality of life and treatment satisfaction [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs PB2056.
11. Kulasekararaj A, Brodsky R, Griffin M, et al. Long-term ravulizumab treatment in complement inhibitor-experienced patients with PNH provides durable control of intravascular hemolysis with low incidence of major adverse vascular events and death [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P772.
12. Jang JH, Kim JS, Lim CT, et al. Lactate dehydrogenase is a predictor of thromboembolism, and thromboembolism is a predictor of death, in patients with paroxysmal nocturnal hemoglobinuria (PNH): results from a Korean PNH registry [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs PB2040.
13. Simon F, Ligtvoet R, Nösslinger T, et al. Safety and treatment adherence with acalabrutinib in very old (≥80Y) and/or frail patients with chronic lymphocytic leukemia (CLL) – interim safety analysis of the ongoing Phase-II CLL-frail trial [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P630.
14. Marconi G, Arslan S, Fleming S, et al. Safety and tolerability of AZD0466 as monotherapy for patients with advanced hematological malignancies – Preliminary results from an ongoing Phase I/II trial [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P537.
15. Valent J, Liedtke M, Zonder J, 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: 18-month results of a Phase 2 study [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs S204.
16. Wechalekar A, Palladini G, Molina MA, et al. Cardiac amyloid reaching for extended survival (CARES) trials: 2 placebo-controlled, double-blind, randomized, Phase 3 trials assessing CAEL-101 in patients with mayo stages IIIA/IIIB AL amyloidosis [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs PB2150.
17. Lo SH, Aggio D, Gatta F, et al. Real-world clinical practices in treatment discontinuation with complement C5 inhibitors for atypical hemolytic uremic syndrome: a global survey of healthcare professionals [abstract]. Presented at the European Hematology Association (EHA) 2023; June 8-11, 2023; Frankfurt, Germany. Abs P1599.