Histone Deacetylase Inhibitor

Beleodaq

Approved 3 Jul 2014IntravenousPowder

Indications

Beleodaq is indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This indication is approved under accelerated approval based on tumor response rate and duration of response [ see Clinical Studies ( 14 )]. 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.

Beleodaq is a histone deacetylase inhibitor indicated for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). 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.( 1 )

Contraindications

None None. ( 4 )

Warnings and precautions

Hematologic Toxicity : Thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia: Monitor blood counts and modify dosage for hematologic toxicities. ( 2.2 , 5.1 ) Infection : Serious and fatal infections (e.g., pneumonia and sepsis) ( 5.2 ) Hepatotoxicity : Beleodaq may cause hepatic toxicity and liver function test abnormalities. Monitor liver function tests and omit or modify dosage for hepatic toxicities.

( 2.2 , 5.3 ) Tumor lysis syndrome : Monitor patients with advanced stage disease and/or high tumor burden and take appropriate precautions ( 5.4 ) Gastrointestinal Toxicity : Nausea, vomiting and diarrhea occur with Beleodaq and may require antiemetic and antidiarrheal medications ( 5.5 ). Embryo-Fetal Toxicity : Can cause fetal harm. ( 5.6 )

5.1Hematologic Toxicity

Beleodaq can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and/or anemia; monitor blood counts weekly during treatment, and modify dosage as necessary [see Dosage and Administration ( 2.2 ) and Adverse Reactions( 6.1 )] .

5.2Infections Serious

and sometimes fatal infections, including pneumonia and sepsis, have occurred with Beleodaq. Do not administer Beleodaq to patients with an active infection. Patients with a history of extensive or intensive chemotherapy may be at higher risk of life threatening infections [see Adverse Reactions ( 6.1 )].

At a glance

Brand name: Beleodaq
Active substance: belinostat
Pharmacologic class: Histone Deacetylase Inhibitor
Route: Intravenous
Dosage form: Powder
Applicant: Acrotech Biopharma
Status: Prescription
FDA approval: 3 Jul 2014
Application: NDA206256-001

Indications

Warnings and precautions

5.1Hematologic Toxicity

5.2Infections Serious

Adverse reactions

The following clinically significant adverse reactions are described in more detail in other sections of the prescribing information.

Hematologic Toxicity [see Warnings and Precautions ( 5.1 )]
Infection [see Warnings and Precautions ( 5.2 )]
Hepatotoxicity [see Warnings and Precautions ( 5.3 )]
Tumor Lysis Syndrome [see Warnings and Precautions ( 5.4 )]
Gastrointestinal Toxicity [see Warnings and Precautions ( 5.5 )] The most common adverse reactions (>25%) are nausea, fatigue, pyrexia, anemia, and vomiting. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Acrotech Biopharma Inc at 1-888-292-9617 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Beleodaq may not reflect the rates observed in practice. Adverse Reactions in Patients with Peripheral T-Cell Lymphoma The safety of Beleodaq was evaluated in 129 patients with relapsed or refractory PTCL in the single arm clinical trial in which patients were administered Beleodaq at a dosage of 1,000 mg/m 2 administered over 30 minutes by IV infusion once daily on Days 1 through 5 of a 21-day cycle [see Clinical Studies ( 14 ) ] .

The median duration of treatment was 2 cycles (range 1 – 33 cycles). The most common adverse reactions observed in the trial of patients with relapsed or refractory PTCL treated with Beleodaq were nausea, fatigue, pyrexia, anemia, and vomiting [see Clinical Studies ( 14 ) ] . Table 3 summarizes the adverse reactions regardless of causality from the trial in patients with relapsed or refractory PTCL. Table 3: Adverse Reactions Occurring in ≥ 10% of Patients with Relapsed or Refractory PTCL (NCI CTC Grade 1-4) Adverse Reactions Percentage of Patients (%) (N=129) All Grades Grade 3 or 4 All Adverse Reactions 97 61 Nausea 42 1 Fatigue 37 5 Pyrexia 35 2 Anemia 32 11 Vomiting 29 1 Constipation 23 1 Diarrhea 23 2 Dyspnea 22 6 Rash 20 1 Peripheral Edema 20 0 Cough 19 0 Thrombocytopenia 16 7 Pruritus 16 3 Chills 16 1 Increased Blood Lactate Dehydrogenase 16 2 Decreased Appetite 15 2 Headache 15 0 Infusion Site Pain 14 0 Hypokalemia 12 4 Prolonged QT 11 4 Abdominal pain 11 1 Hypotension 10 3 Phlebitis 10 1 Dizziness 10 0 Note: Adverse reactions are listed by order of incidence in the “All Grades” category first, then by incidence in “the Grade 3 or 4” category; Measured by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version

3.0Serious Adverse Reactions

Sixty-one patients (47.3%) experienced serious adverse reactions while taking Beleodaq or within 30 days after their last dose of Beleodaq. The most common serious adverse reactions (> 2%) were pneumonia, pyrexia, infection, anemia, increased creatinine, thrombocytopenia, and multi-organ failure. One treatment-related death associated with hepatic failure was reported in the trial. One patient with baseline hyperuricemia and bulky disease experienced Grade 4 tumor lysis syndrome during the first cycle of treatment and died due to multi-organ failure.

A treatment-related death from ventricular fibrillation was reported in another monotherapy clinical trial with Beleodaq. ECG analysis did not identify QTc prolongation. Discontinuations due to Adverse Reactions Twenty-five patients (19.4%) discontinued treatment with Beleodaq due to adverse reactions. The adverse reactions reported most frequently as the reason for discontinuation of treatment included anemia, febrile neutropenia, fatigue, and multi-organ failure.

Dosage Modifications due to Adverse Reactions In the trial, dosage adjustments due to adverse reactions occurred in 12% of Beleodaq-treated patients.

Beleodaq

Indications

Contraindications

Warnings and precautions

5.1Hematologic Toxicity

5.2Infections Serious

At a glance

Two medicines in one question?

Beleodaq

Indications

Contraindications

Warnings and precautions

5.1Hematologic Toxicity

5.2Infections Serious

At a glance

Two medicines in one question?

5.3Hepatotoxicity

5.4Tumor Lysis Syndrome

5.5Gastrointestinal Toxicity

5.6Embryo-fetal Toxicity Based

Interactions

7.1UGT1A1 Inhibitors

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

Adverse reactions

6.1Clinical Trials Experience

3.0Serious Adverse Reactions

Composition

Official product information