FDA grants accelerated approval to acalabrutinib for mantle cell lymphoma

On October 31, 2017, the Food and Drug Administration 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.

Approval was based on Study LY-004, an open-label, phase 2 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 anemia, thrombocytopenia, headache, neutropenia, diarrhea, 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 anemia.

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

Full dosing information is available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/210259s000lbl.pdf

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. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics, available at: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf.

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 by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Follow the Oncology Center of Excellence on Twitter @FDAOncology.