The recent first global approval of acalabrutinib has been reviewed in detail in the First Global Approval report in Adis’ journal Drugs, based on the development milestones tracked in AdisInsight.
In October 2017, acalabrutinib (Calquence®), developed by Acerta Pharma, received its first global approval in the US for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. This was an accelerated approval granted to AstraZenea Pharmaceuticals (parent of Acerta Pharma). In addition the application was granted Priority Review and Breakthrough Therapy designations.
Acalabrutinib is an orally administered Bruton’s tyrosine kinase (BTK) inhibitor that has a downstream effect on B-cell receptor signalling pathways and essentially interrupts the activation of several tumour cell survival pathways.
MCL is a rare form of non-Hodgkin lymphoma, accounting for up to 10% of lymphomas, with an estimated prevalence of 1 in 25,000 people; males are 4 times more likely than females to present with the disease.
Acalabrutinib has been granted Orphan Drug status, and the accelerated approval was based on data from a single-arm trial that included 124 patients (ACE-LY-004). The continued approval of acalabrutinib in this indication may be contingent on further clinical trials that verify and further describe the clinical effect of the agent.
Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research described MCL as “a particularly aggressive cancer”, and went on to explain that, “for patients who have not responded to treatment or have relapsed, Calquence provides a new treatment option that has shown high rates of response for some patients in initial studies.”
The most commonly reported adverse events occurring in at least 20% of patients include anaemia, thrombocytopenia, headache, neutropenia, diarrhoea, fatigue, myalgia, and bruising. Major warnings and precautions noted in the prescribing information include haemorrhage, infections, cytopenias, second primary malignancies, and atrial fibrillation and flutter.