On February 22, AstraZeneca announced that 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.
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity. In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.
Calquence is 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.
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.
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. The tablet can be taken with gastric acid-reducing agents, including proton pump inhibitors (PPIs), antacids and H2-receptor antagonists (H2RAs). The majority of observed adverse events (AEs) in these studies were mild with no new safety concerns identified.
About Chronic Lymphocytic Leukaemia (CLL)
Chronic Lymphocytic Leukaemia (CLL) is the most prevalent type of leukaemia in adults, with over 100,000 new cases globally in 2019. 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.
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. B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.
