Abexinostat (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

, 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 The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are Tumors of the hematopoietic and lymphoid tissues, "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. ...

. 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 Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

and inhibits

RAD51 DNA repair protein RAD51 homolog 1 is a protein encoded by the gene ''RAD51''. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of DNA double strand breaks. RAD51 family members are homologous to t ...

, 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 The phases of clinical research are the stages in which scientists conduct experiments with a health intervention to obtain sufficient evidence for a process considered effective as a medical treatment. For drug development, the clinical phases ...

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 Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredn ...

(NHL) and

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

(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 Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific subs ...

profile and oral dosing schedule, allowing for continuous exposure at concentrations required for efficient tumor cell killing.

References

{{HDAC inhibitors Benzofuran-2-carboxamides Hydroxamic acids Histone deacetylase inhibitors Antineoplastic drugs Experimental cancer drugs Benzamides 2-Phenoxyethanamines