FDA Grants Accelerated Approval to Acalabrutinib for Mantle Cell Lymphoma

A second generation BTK inhibitor is more potent and selective than ibrutinib

On 31 October 2017, the US Food and Drug Administration (FDA) granted accelerated approval to acalabrutinib (Calquence, AstraZeneca Pharmaceuticals Inc. under license of Acerta Pharma BV) for treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.

Acalabrutinib is a second generation Bruton's tyrosine kinase (BTK) inhibitor, more potent and selective (fewer side-effects) than ibrutinib, the first-in-class BTK inhibitor.

Approval was based on Study LY-004, an open-label, phase II trial (NCT02213926) enrolling 124 patients with MCL who received at least one prior therapy. Patients received acalabrutinib, 100 mg orally twice daily, until disease progression or unacceptable toxicity.

The overall response rate (investigator assessed), which was the primary endpoint, was 81% (95% CI: 73%, 87%); and the complete response rate was 40% (95% CI: 31%, 49%). There was excellent concordance (91%) between the ORR as determined by investigator assessment and independent review committee. The median duration of response has not been reached with 15.2 months of follow-up. The median time to best response was 1.9 months.

The most common adverse reactions in greater than 20% of patients taking acalabrutinib were anaemia, thrombocytopenia, headache, neutropenia, diarrhoea, fatigue, myalgia and bruising. Dose reductions or discontinuations due to adverse reactions were reported in 1.6% and 6.5% of patients, respectively. The most frequently reported (≥5%) grade 3 or 4 adverse reactions were neutropenia, thrombocytopenia and anaemia.

The recommended dose is 100 mg orally twice daily, approximately every 12 hours.

Full dosing information is available here

FDA granted Breakthrough Therapy, Orphan Drug designation, and priority review to acalabrutinib for this indication. Approval was granted approximately 14 weeks prior to the due date.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.