BTK Inhibitor Granted Breakthrough Therapy Designation for Mantle Cell Lymphoma


Acalabrutinib has been granted FDA Breakthrough Therapy Designation for the treatment of patients with mantle cell lymphoma who have relapsed or have received at least one prior therapy.

Clinicians may soon have a new tool for combating mantle cell lymphoma (MCL) in patients who have relapsed or have received at least one prior therapy. AstraZeneca announced on August 1, 2017 that the US Food and Drug Administration (FDA) is granting Breakthrough Therapy Designation for the Bruton tyrosine kinase (BTK) inhibitor acalabrutinib.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said new treatments are urgently needed for MCL patients who relapse or do not respond to current therapy. He said this new designation for acalabrutinib will help expedite getting this potential treatment to patients who have very limited treatment options.

A highly selective, potent BTK inhibitor, acalabrutinib is in development for the treatment of multiple B-cell cancers. The breakthrough designation is assigned to new medicines for a serious condition in which encouraging early clinical results demonstrate substantial improvement on a clinically significant endpoint compared with available medicines.

This new designation is based on the totality of clinical data from the acalabrutinib development program, including data from the phase II ACE-LY-004 clinical trial in patients with relapsed or refractory MCL. The results from the ACE-LY-004 clinical trial will be submitted for presentation at an upcoming medical congress, according to a spokesperson at AstraZeneca.  The data are not publicly available at this point.

“Ibrutinib, the first BTK inhibitor, is routinely used to treat CLL and mantle cell lymphoma. Acalabrutinib promises to be more tolerable than ibrutinib due to its minimal off-target activity. However, it remains to be seen whether it is truly better than the existing option,” said Pallawi Torka, MD, Assistant Professor of Oncology and Co-Director of the Hematology Oncology Fellowship Program at Roswell Park Cancer Institute, Buffalo, New York.

The acalabrutinib development program includes both monotherapy and combination therapy strategies in chronic lymphocytic leukemia (CLL), MCL, Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma, as well as monotherapy and combination trials in solid tumors.

Dr. Torka said BTK inhibitors offer new hope for a significant number of patients. “BTK inhibitors have been a major advance in the treatment of lymphomas, as they combine efficacy with good tolerance. While on one hand they have the capability of overcoming poor prognosis portended by deleterious mutations such as p53, they also allow for elderly patients with borderline performance status to maintain quality of life while on therapy,” Dr. Torka told OncoTherapy Network.

Acalabrutinib was granted Orphan Drug Designation by the FDA for the treatment of patients with MCL in September 2015 and by the European Commission in March 2016 for the treatment of patients with CLL, MCL, and WM. MCL is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis. The median age at diagnosis is 68 years, and it is three times more common in men than women.

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