BELEODAQ™ (belinostat) for injection

a pan HDAC inhibitor
BELEODAQ (belinostat) injection, powder, lyophilized, for solution
[Spectrum Pharmaceuticals, Inc.] 

Target Indications

• Peripheral T-Cell Lymphoma (PTCL)
• Carcinoma of Unknown Primary (CUP)
• Non-Small Cell Lung Cancer (NSCLC)
• Other solid tumors and hematological malignancies

Route of Administration

• IV

Mode of Action

BELEODAQ (PXD 101) is a pan HDAC inhibitor in late stage clinical development with more than 1,000+ patients treated to date. BELEODAQ is believed to inhibit enzymatic activity of class 1 and class 2 HDACs. BELEODAQ is also believed to increase in acetylation of both histone and histone proteins, resulting in cell cycle arrest, apoptosis and a decrease in cell proliferation.

Status

Currently in a Pivotal study in PTCL

In clinical trials, BELEODAQ has shown that it may be well-tolerated, which allows for combination with traditional chemotherapy without causing excessive bone marrow toxicity. In pre-clinical studies BELEODAQ has shown to be active against multiple cancers by inhibiting cell proliferation (inhibiting cancer growth) and inducing programed cell death ("apoptosis") in tumor cells (the tumor cells are forced to self-destruct).

BELEODAQ has been eva luated in a number of Phase 1 and 2 clinical trials in hematological cancers and solid tumors. Data from these trials have provided for the anti-tumor effect of BELEODAQ as monotherapy in peripheral T-cell lymphomas (PTCL) and in combination with other anti-cancer drugs for the treatment of multiple types of cancer including CUP and non-small cell lung cancer (NSCLC).

To date clincal trials suggest BELEODAQ is well tolerated at full dose. The most frequent adverse events of any grade and irrespective of study design have been nausea, fatigue and vomiting. As such, it is being investigated in high doses not only alone, but also in drug combinations. In preclinical tumor models, BELEODAQ is active in cancer cells that have become resistant to existing chemotherapies. BELEODAQ could add substantial treatment value to several important drug combinations.

The FDA granted approval of BELEODAQ for relapsed or refractory PTCL on July 3, 2014.

Continued support from the National Cancer Institute (NCI) has helped build a comprehensive program which has identified the optimal development route for BELEODAQ. The development of BELEODAQ is planned in collaboration with the NCI, and all trials are born from laboratory data showing the most favorable methods of use and combinations.

Based on available data so far, Spectrum believes that BELEODAQ has the potential to become the "best in class" pan HDAC inhibitor. The efficacy of BELEODAQ noted in ongoing clinical trials is likely to be linked to the high blood concentrations of drug achieved using intravenous ("IV") dosing. This high blood concentration may not be attainable for other pan HDAC inhibitors. BELEODAQ has also exhibited a favourable safety profile.

详细的资料
Label (PDF)¹²
Letter (PDF)¹³  


 

Beleodaq (belinostat) for Injection
Company:  Spectrum Pharmaceuticals, Inc.
Application No.:  206256
Approval Date: 7/03/2014

Persons with disabilities having problems accessing the PDF files below may call (301) 796-3634 for assistance.

• Approval Letter(s) (PDF)
• Printed Labeling (PDF)
• Summary Review (PDF)
• Officer/Employee List (PDF)
• Office Director Memo (PDF)
• Cross Discipline Team Leader Review (PDF)
• Medical Review(s) (PDF)
• Chemistry Review(s) (PDF)
• Pharmacology Review(s) (PDF)
• Statistical Review(s) (PDF)
• Microbiology Review(s) (PDF)
• Clinical Pharmacology Biopharmaceutics Review(s) (PDF)
• Risk Assessment and Risk Mitigation Review(s) (PDF)
• Proprietary Name Review(s) (PDF)
• Other Review(s) (PDF)
• Administrative Document(s) & Correspondence (PDF)

2014年7月4日,美国FDA宣布批准由Spectrum生物医药公司开发的用于治疗T细胞淋巴瘤药物belinostat上市，这种药物将以Beleodaq的商品名出售。外周T细胞淋巴瘤是一种罕见并发展迅速的非霍奇金淋巴瘤淋巴瘤。这种疾病每年会杀死18990名患者。此次批准的Beleodaq是一种组蛋白脱乙酰酶抑制剂。也是自2009年至今批准的第三种治疗这种疾病的药物。这一药物的批准也意味着Spectrum公司获得了BioAlliance Pharma公司的里程碑基金。

根据一项有129名患者参与的临床三期研究，使用Beleodaq的患者有25.8%病情得到改善。而患者常见的副作用主要是贫血、疲劳、发热、恶心呕吐等。

英文名		Belinostat
别名		PXD101; N-Hydroxy-3-(3-phenylsulfamoylphenyl)acrylamide
产品名称		Belinostat; PXD101; N-羟基-3-(3-苯基氨基磺酰基苯基)丙烯酰胺
分子结构
分子式		C15H14N2O4S
分子量		318.35
CAS 登录号		414864-00-9

Beleodaq is a histone deacetylase inhibitor with a sulfonamide-hydroxamide structure. The chemical name of belinostat is (2E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide. The structural formula is as follows:

The molecular formula is C15H14N2O4S and the molecular weight is 318.35 g/mol.

Belinostat is a white to off-white powder. It is slightly soluble in distilled water (0.14 mg/mL) and polyethylene glycol 400 (about 1.5 mg/mL), and is freely soluble in ethanol (> 200 mg/mL). The pKa values are 7.87 and 8.71 by potentiometry and 7.86 and 8.59 by UV.

Beleodaq (belinostat) for injection is supplied as a sterile lyophilized yellow powder containing 500 mg belinostat as the active ingredient. Each vial also contains 1000 mg L-Arginine, USP as an inactive ingredient. The drug product is supplied in a single-use 30 mL clear glass vial with a coated stopper and aluminum crimp seal with “flip-off” cap. Beleodaq is intended for intravenous administration after reconstitution with 9 mL Sterile Water for injection, and the reconstituted solution is further diluted with 250 mL of sterile 0.9% Sodium Chloride injection prior to infusion [see Dosage and Administration (2)].