Abexinostat

Abexinostat (INN, formerly PCI-24781) is an experimental drug candidate for cancer treatment. It was developed by Pharmacyclics and licensed to Xynomic. , it was in Phase II clinical trials for B-cell lymphoma. Pre-clinical study suggests the potential for treatment of different types of cancer as well.

Abexinostat exerts its effect as a pan-histone deacetylase inhibitor and inhibits RAD51, which is involved in repairing DNA double strand breaks.

Progress
Abexinostat has been granted a fast track designation by the FDA for the treatment of patients with relapsed or refractory follicular lymphoma in the fourth-line setting. This designation is significant as it aims to expedite the development and review of drugs intended to treat serious conditions and fill an unmet medical need.

Research
The FORERUNNER conducted a study, a potentially pivotal phase II trial of abexinostat monotherapy in patients with relapsed/refractory follicular lymphoma, in the United States and Europe. In the phase II study, abexinostat showed a modest overall response rate (ORR) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), with a notably higher ORR observed in patients with follicular lymphoma. This study involved 100 patients treated with 80 mg of abexinostat twice daily for 14 days of a 21-day cycle. The ORR for follicular lymphoma specifically was 56%, indicating a significant impact on this lymphoma subtype. The study also reported grade ≥3 adverse events in a considerable number of patients, with thrombocytopenia, neutropenia, and anemia being the most frequently reported.

Safety and efficacy
Abexinostat has been characterized by its unique pharmacokinetic profile and oral dosing schedule, allowing for continuous exposure at concentrations required for efficient tumor cell killing.