Calquence tablet formulation approved in the EU for patients with chronic lymphocytic leukaemia

Tablet formulation can be co-administered with gastric acid-reducing agents allowing greater patient and physician choice.
Approval based on ELEVATE-PLUS trials which showed bioequivalence and consistent dosing vs. current capsule.

AstraZeneca’s tablet formulation of Calquence (acalabrutinib) has been approved in the European Union (EU) for the treatment of adult patients with chronic lymphocytic leukaemia (CLL).

The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the ELEVATE-PLUS trials published in the American Society of Haematology journal, Blood.¹

In the trials, results showed the Calquence capsule and tablet formulations are bioequivalent, indicating the same efficacy and safety profile can be expected when prescribed with the same dosing strength and schedule.¹The tablet can be taken with gastric acid-reducing agents, including proton pump inhibitors (PPIs), antacids and H2-receptor antagonists (H2RAs).¹The majority of observed adverse events (AEs) in these studies were mild with no new safety concerns identified.¹

Paolo Ghia, MD, Director, Strategic Research Program on CLL, Università Vita-Salute San Raffaele in Milan, said: “Many patients with chronic lymphocytic leukaemia face multiple medical conditions that require daily treatment, including the use of acid-reducing agents for conditions such as gastro-oesophageal reflux. The tablet formulation allows for co-administration with these drugs, allowing more patients with chronic lymphocytic leukaemia to assume Calquence.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The Calquence tablet formulation underscores our commitment to understanding the needs of the chronic lymphocytic leukaemia community and providing patient-oriented treatment solutions. Today’s approval offers physicians and patients in the EU more flexibility to determine the right treatment plan and enables more patients to potentially benefit from this medicine.”

Calquenceis approved as a capsule formulation for CLL in the EU. It is also approved in the US as a capsule and tablet formulation for patients with CLL, small lymphocytic lymphoma (SLL) and relapsed or refractory mantle cell lymphoma (MCL). Additionally, Calquence is approved as a capsule formulation in many other countries worldwide. Indications may vary by market.

Notes

CLL
CLL is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019.² Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.³

In CLL, there is an accumulation of abnormal lymphocytes within the bone marrow and in blood and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets. This could result in anaemia, infection and bleeding.⁴ B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

ELEVATE-PLUS
ELEVATE-PLUS is comprised of three Phase I, open-label, single-dose, cross-over studies conducted in 116 healthy subjects. The trials established bioequivalence between acalabrutinib tablets (100mg) and acalabrutinib (100mg) capsules, evaluated the PPI effect of acalabrutinib tablets administered in the presence versus absence of PPI rabeprazole and investigated the effect of food by comparing acalabrutinib tablets administered with a high-fat diet versus fasted.¹

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquencebinds covalently to BTK, thereby inhibiting its activity.^5,6 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.⁵

Calquence is available for prescribing in capsule and tablet formulations in the US and EU for the treatment of CLL. Capsules have restrictions in relation to use with gastric acid reducing agents.

Calquence capsules are approved for CLL in Japan, Canada, Australia and many other countries worldwide.

In the US and several other countries, Calquence capsules are also approved for the treatment of adult patients with MCL who have received at least one prior therapy. The US MCL 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 not currently approved for the treatment of MCL in Europe or Japan.

As part of an extensive clinical development programme, AstraZeneca and Acerta Pharma are currently evaluating Calquence in more than 20 company-sponsored clinical trials. Calquence is being evaluated for the treatment of multiple B-cell blood cancers, including CLL, MCL, diffuse large B-cell lymphoma, Waldenström’s macroglobulinaemia, follicular lymphoma and marginal zone lymphoma.

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

AstraZeneca
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References

1. Sharma S, Pepin X, Burri H, et al. Bioequivalence and relative bioavailability studies to assess a new acalabrutinib formulation that enables coadministration with proton-pump inhibitors. Clin Pharmacol Drug Dev. 2022;11: 1294-1307.
2. Yao Y, Lin X, Li F, et al. The global burden and attributable risk factors of chronic lymphocytic leukemia in 204 countries and territories from 1990 to 2019: analysis based on the global burden of disease study 2019. Biomed Eng Online. 2022;1: 4.
3. American Cancer Society. Signs and Symptoms of Chronic Lymphocytic Leukemia. Accessed online. Accessed June 2022.
4. National Cancer Institute. Chronic lymphocytic leukemia treatment (PDQ®)–Patient version. Accessed online. Accessed June 2022.
5. Calquence® (acalabrutinib) [prescribing information]. Wilmington, DE; AstraZeneca Pharmaceuticals LP; 2019.
6. Wu J, Zhang M, Liu D. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor. J Hematol Oncol. 2016;9(21).