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FDA approval of acalabrutinib for adult patients with CLL or SLL

Nov 27, 2019

On the 21 stNovember 2019, the U.S. Food and Drug Administration (FDA)approved acalabrutinib for the treatment of adult patients with chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL). 1This is the second approval to be granted by Project Orbis, an initiative of the US FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicines among international partners. 2,3

Acalabrutinib, a second-generation selective inhibitor of Bruton’s tyrosine kinase (BTK), is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. 4The supplemental approval of the new indications is based on the results of two phase III randomized clinical trials: ELEVATE-TN ( NCT02475681) and ASCEND ( NCT02970318).

The ELEVATE-TN trial included 535 patients with previously untreated CLL who were randomized (1:1:1) into three treatment arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, and chlorambucil plus obinutuzumab. With a median follow-up of 28.3 months, profession-free survival (PFS; IRC-assessed) was significantly improved in both acalabrutinib arms compared with chlorambucil chemotherapy plus obinutuzumab. 1The interim analysis results will be presented at the upcoming American Society of Hematology congress. 5

In the ASCEND trial, 310 patients with relapsed/refractory CLL were randomized (1:1) into two treatment groups: acalabrutinib monotherapy or rituximab with investigator’s choice of idelalisib or bendamustine. Results showed a statistically significant and clinically meaningful improvement in PFS (IRC-assessed) with acalabrutinib monotherapy compared with the second treatment group. 6

Across both studies, the safety and tolerability of acalabrutinib were consistent with the known profile. The most common adverse effects observed were anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. 2

The acalabrutinib clinical development program is ongoing in various hematologic malignancies including CLL, MCL, diffuse large B-cell lymphoma, and Waldenström macroglobulinaemia. 7

  1. U.S. Food and Drug Administration. Project Orbis: FDA approves acalabrutinib for CLL and SLL. https://www.fda.gov/drugs/resources-information-approved-drugs/project-orbis-fda-approves-acalabrutinib-cll-and-sll.[Accessed 26 November 2019]
  2. U.S. Food and Drug Administration. FDA takes second action under international collaboration, approves new treatment option for patients with chronic lymphocytic leukemia. https://www.fda.gov/news-events/press-announcements/fda-takes-second-action-under-international-collaboration-approves-new-treatment-option-patients. [Accessed 26 November 2019]
  3. U.S. Food and Drug Administration. Project Orbis. https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis.[Accessed 26 November 2019]
  4. CALQUENCE® (acalabrutinib) Prescribing Information. https://www.azpicentral.com/calquence/calquence.pdf#page=1. [Accessed 26 November 2019]
  5. Sharman J.P. et al. Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naïve Chronic Lymphocytic Leukemia (CLL). 2019 Dec 07. Oral Abstract #31: American Society of Hematology 2019 Annual Meeting and Exposition, Orlando, FL
  6. AstraZeneca. Press Release. Calquence Phase III ASCEND trial met primary endpoint at interim analysis in relapsed or refractory chronic lymphocytic leukaemia and will stop early. https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-phase-iii-ascend-trial-met-primary-endpoint-at-interim-analysis-in-relapsed-or-refractory-chronic-lymphocytic-leukaemia-and-will-stop-early-07052019.html.[Accessed 27 November 2019]
  7. AstraZeneca. Press Release. Available at: https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-approved-in-the-us-for-adult-patients-with-chronic-lymphocytic-leukaemia-21112019.html.[Accessed 27 November 2019]