General Information

Beleodaq (belinostat) is a histone deacetylase inhibitor.

Beleodaq is specifically indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma. 

Beleodaq is supplied as a solution for intravenous infusion. The recommended dosage of Beleodaq is 1,000 mg/m2
administered over 30 minutes by intravenous infusion once daily on Days 1-5 of a 21-day cycle. Cycles can be repeated every 21 days until disease progression or unacceptable toxicity. 

Mechanism of Action

Beleodaq (belinostat) is a histone deacetylase inhibitor. HDACs catalyze the removal of acetyl groups from the lysine residues of histones and some non-histone proteins. In vitro, belinostat caused the accumulation of acetylated histones and other proteins, inducing cell cycle arrest and/or apoptosis of some transformed cells. Belinostat shows preferential cytotoxicity towards tumor cells compared to normal cells.

Side Effects

Adverse effects associated with the use of Beleodaq may include, but are not limited to, the following:

• nausea
• fatigue
• pyrexia 
• anemia
• vomiting

Clinical Trial Results

This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.

The FDA approval of Beleodq for PTCL was based on an open-label, single-arm, non-randomized international trial conducted at 62 centers in 129 subjects with relapsed or refractory PTCL. The subjects were treated with Beleodaq 1,000 mg/m2 administered over 30 minutes via IV infusion once daily on Days 1-5 of a 21-day cycle. Subjects were treated with repeat cycles every three weeks until disease progression or unacceptable toxicity. The primary efficacy endpoint was response rate (complete response and partial response) as assessed by an independent review committee (IRC) using the International Workshop Criteria (IWC). The key secondary efficacy endpoint was duration of response. Response assessments were evaluated every 6 weeks for the first 12 months and then every 12 weeks until 2 years from the start of study treatment. Duration of response was measured from the first day of documented response to disease. There were 120 subjects who had histologically confirmed PTCL by central review evaluable for efficacy. In all evaluable subjects (N = 120) treated with Beleodaq, the overall response rate was 25.8% (n = 31) with rates of 23.4% for PTCL, unspecified and 45.5% for Angioimmunoblastic T-cell lymphoma, the two largest subtypes enrolled. The median duration of response based on the first date of response to disease progression or death was 8.4 months. Of the responders, the median time to response was 5.6 weeks.