FDA Awards Acalabrutinib Priority Review in MCL

The FDA has granted a priority review to a new drug application for acalabrutinib for patients with previously-treated mantle cell lymphoma.

Flavia Borellini, PhD

The FDA has granted a priority review to a new drug application (NDA) for acalabrutinib for patients with previously-treated mantle cell lymphoma (MCL), according to AstraZeneca, the manufacturer of the highly selective, potent BTK inhibitor.

UPDATE: The FDA Approved Acalabrutinib for MCL on October 31, 2017

The announcement comes just 1 day after AstraZeneca reported that acalabrutinib had received an FDA breakthrough therapy designation in this setting. The NDA is supported, in part, with phase II results from the ACE-LY-004 trial evaluating the safety and efficacy of acalabrutinib in patients with relapsed/refractory MCL. The company has not made any data from that trial available, but a spokesperson wrote in an email to OncLive that the data is slated to be presented at a medical meeting later this year.

Under the Prescription Drug User Fee Act, the FDA is scheduled to issue its final approval decision for acalabrutinib in this setting by early next year.

Acerta Pharma, AstraZeneca’s hematology research and development center of excellence, developed acalabrutinib to treat multiple B-cell cancers, including multiple myeloma and chronic lymphocytic leukemia (CLL), alone or in combination. The company is currently recruiting patients with previously untreated MCL for the phase III ACE-LY-308 clinical trial evaluating acalabrutinib in combination with bendamustine and rituximab (BR) versus placebo plus BR.

“We believe acalabrutinib has the potential to be a very important treatment option for patients with this life-threatening blood cancer,” Flavia Borellini, PhD, Acerta Pharma CEO, said in a press release. “The FDA’s NDA acceptance exemplifies our progress in the acalabrutinib development program and continues our momentum as we seek to transform care for people with hematologic malignancies.”

MCL is an aggressive B-cell non-Hodgkin lymphoma with a poor prognosis. The disease accounts for up to 6% of new non-Hodgkin lymphoma cases in Western countries each year, with an annual incidence of 0.5 per 100,000 persons and an estimated prevalence of 3.5 per 100,000.

Patients with advanced MCL have seen an increase in treatment options in recent years. In 2013, the FDA approved ibrutinib (Imbruvica) for patients with MCL who have received at least 1 prior therapy, and lenalidomide (Revlimid) for patients who have relapsed or whose disease has progressed after 2 prior therapies, including at least 1 prior treatment with bortezomib (Velcade).

Bortezomib was approved for patients with previously treated MCL in 2006 and for previously untreated patients in 2014.

Available data for acalabrutinib have demonstrated promising activity in patients with CLL and small lymphocytic leukemia (SLL). Results from the phase I/II ACE-CL-001 trial presented at the 2016 ASH Annual Meeting showed that the overall response rate (ORR) was 79% with acalabrutinib in patients with ibrutinib-intolerant CLL/SLL.1

Of 29 patients evaluable for response, best response was a complete response (CR) in 1 patient (3.4%), a partial response (PR) in 15 (51.7%), PR with lymphocytosis (PRL) in 7 (24.1%), and stable disease (SD) in 6 (20.7%). The ORR when including only CR plus PR was 55.2%, and was 79.3% when including PRL in the ORR definition. All evaluable patients achieved at least SD. The median time to PRL or better was 1.9 months.

In a separate abstract presented at the 2016 ASH Annual Meeting, acalabrutinib demonstrated an ORR of 38.1% in a cohort of patients with Richter transformation from the same ACE-CL-001 trial.2


  1. Awan FT, Schuh A, MD PhD, Brown JR, et al. Acalabrutinib monotherapy in patients with ibrutinib intolerance: Results from the phase 1/2 ACE-CL-001 clinical study. Presented at: American Society of Hematology 58th Annual Meeting; December 3-6, 2016; San Diego, CA. Abstract 638.
  2. Hillmen P, Schuh A, Eyre TA, et al. Acalabrutinib Monotherapy in Patients with Richter Transformation from the Phase 1/2 ACE-CL-001 Clinical Study. 58th ASH Annual Meeting and Exposition; San Diego, California; December 2-6, 2016. Abstract 60.