Brand Name
Besponsa
Generic Name
Inotuzumab Ozogamicin
View Brand Information FDA approval date: August 18, 2017
Classification: CD22-directed Immunoconjugate
Form: Injection
What is Besponsa (Inotuzumab Ozogamicin)?
BESPONSA is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia . BESPONSA is a CD22-directed antibody-drug conjugate indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia .
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Brand Information
Besponsa (inotuzumab ozogamicin)
1INDICATIONS AND USAGE
BESPONSA is indicated for the treatment of relapsed or refractory
2DOSAGE FORMS AND STRENGTHS
For injection: 0.9 mg as a white to off-white lyophilized powder in a single-dose vial for reconstitution and further dilution.
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the label:
- Hepatotoxicity, including hepatic VOD (also known as SOS)
- Increased risk of post-transplant non-relapse mortality
- Myelosuppression
- Infusion related reactions
- QT interval prolongation
4.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Relapsed or Refractory B-cell Precursor ALL
Adult Patients
The safety of BESPONSA was evaluated in adult patients with relapsed or refractory B-cell precursor ALL in the INO-VATE ALL trial. The study was a randomized clinical study of BESPONSA (n=164) versus Investigator’s choice of chemotherapy (fludarabine + cytarabine + granulocyte colony-stimulating factor [FLAG], mitoxantrone + cytarabine [MXN/Ara-C], or high dose cytarabine [HIDAC]) (n=143)
Of the 164 patients who received BESPONSA, the median age was 47 years (range: 18–78 years), 56% were male, 68% had received 1 prior treatment regimen for ALL, 31% had received 2 prior treatment regimens for ALL, 68% were White, 19% were Asian, and 2% were Black.
In patients who received BESPONSA, the median duration of treatment was 8.9 weeks (range: 0.1–26.4 weeks), with a median of 3 treatment cycles started in each patient. In patients who received Investigator's choice of chemotherapy, the median duration of treatment was 0.9 weeks (range: 0.1–15.6 weeks), with a median of 1 treatment cycle started in each patient.
In patients who received BESPONSA, the most common (≥ 20%) adverse reactions were thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, transaminases increased, abdominal pain, gamma-glutamyltransferase increased, and hyperbilirubinemia.
In patients who received BESPONSA, the most common (≥ 2%) serious adverse reactions were infection, febrile neutropenia, hemorrhage, abdominal pain, pyrexia, VOD, and fatigue.
In patients who received BESPONSA, the most common (≥ 2%) adverse reactions reported as the reason for permanent discontinuation were infection (6%), thrombocytopenia (2%), hyperbilirubinemia (2%), transaminases increased (2%), and hemorrhage (2%); the most common (≥ 5%) adverse reactions reported as the reason for dosing interruption were neutropenia (17%), infection (10%), thrombocytopenia (10%), transaminases increased (6%), and febrile neutropenia (5%); and the most common (≥ 1%) adverse reactions reported as the reason for dose reduction were neutropenia (1%), thrombocytopenia (1%), and transaminases increased (1%).
VOD was reported in 23/164 patients (14%) who received BESPONSA during or following treatment or following a HSCT after completion of treatment
Table 7 shows the adverse reactions with ≥ 10% incidence reported in patients with relapsed or refractory ALL who received BESPONSA or Investigator's choice of chemotherapy.
Additional adverse reactions (all grades) that were reported in less than 10% of patients treated with BESPONSA included: lipase increased (9%), abdominal distension (6%), amylase increased (5%), hyperuricemia (4%), ascites (4%), infusion related reaction (2%; includes the following: hypersensitivity and infusion related reaction), pancytopenia (2%; includes the following: bone marrow failure, febrile bone marrow aplasia, and pancytopenia), tumor lysis syndrome (2%), and electrocardiogram QT prolonged (1%).
Table 8 shows the clinically important laboratory abnormalities reported in patients with relapsed or refractory ALL who received BESPONSA or Investigator's choice of chemotherapy.
Pediatric Patients
The safety of BESPONSA in pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor ALL was evaluated in a multicenter, single-arm, open-label study (ITCC-059)
Serious adverse reactions occurred in 62% of patients who received BESPONSA. Serious adverse reactions in > 2% of patients included infection (21%), febrile neutropenia (17%), VOD (15%), hemorrhage (4%), pyrexia (6%) and multiorgan failure (2%). Fatal adverse reactions occurred in 8% of patients who received BESPONSA, including multiorgan failure, lung infection, sepsis, and encephalopathy.
Permanent discontinuation of BESPONSA due to an adverse reaction occurred in 21% of patients. Adverse reactions which resulted in permanent discontinuation of BESPONSA in 2 or more patients included ALT increased and platelet count decreased.
Dosage interruptions of BESPONSA due to an adverse reaction occurred in 11% of patients. Adverse reactions which required dosage interruption of BESPONSA in 6 patients included increased transaminases, febrile neutropenia, and headache.
The most common adverse reactions (≥ 20%), including laboratory abnormalities, were thrombocytopenia, pyrexia, anemia, vomiting, infection, hemorrhage, neutropenia, nausea, leukopenia, febrile neutropenia, increased transaminases, abdominal pain, and headache.
Table 9 summarizes the adverse reactions in ITCC-059.
Table 10 summarizes select laboratory abnormalities in pediatric patients with CD22-positive relapsed/refractory ALL after receiving BESPONSA monotherapy in Study WI203581 (ITCC-059).
5DESCRIPTION
Inotuzumab ozogamicin is a CD22-directed antibody and cytotoxic-drug conjugate (ADC) consisting of 3 components: 1) the recombinant humanized immunoglobulin class G subtype 4 (IgG4) kappa antibody inotuzumab, specific for human CD22, 2) N-acetyl-gamma-calicheamicin that causes double-stranded DNA breaks, and 3) an acid-cleavable linker composed of the condensation product of 4-(4'-acetylphenoxy)-butanoic acid (AcBut) and 3-methyl-3-mercaptobutane hydrazide (known as dimethylhydrazide) that covalently attaches N-acetyl-gamma-calicheamicin to inotuzumab.
Inotuzumab ozogamicin has an approximate molecular weight of 160 kDa. The average number of calicheamicin derivative molecules conjugated to each inotuzumab molecule is approximately 6 with a distribution from 2–8. Inotuzumab ozogamicin is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells, and the semisynthetic calicheamicin derivative is produced by microbial fermentation followed by synthetic modification.
BESPONSA (inotuzumab ozogamicin) for injection is supplied as a sterile, white to off-white, preservative-free, lyophilized powder for intravenous administration. Each single-dose vial delivers 0.9 mg inotuzumab ozogamicin. Inactive ingredients are polysorbate 80 (0.36 mg), sodium chloride (2.16 mg), sucrose (180 mg), and tromethamine (8.64 mg). After reconstitution with 4 mL of Sterile Water for Injection, USP, the final concentration is 0.25 mg/mL of inotuzumab ozogamicin with a deliverable volume of 3.6 mL (0.9 mg) and a pH of approximately 8.0.
6REFERENCES
- OSHA Hazardous Drugs.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
BESPONSA (inotuzumab ozogamicin) for injection is supplied as a white to off-white lyophilized powder in a single-dose vial for reconstitution and further dilution. Each vial delivers 0.9 mg inotuzumab ozogamicin. Each carton (NDC 0008-0100-01) contains one single-dose vial.
Storage and Handling
Refrigerate (2-8°C; 36-46°F) BESPONSA vials and store in the original carton to protect from light. Do not freeze.
BESPONSA is a hazardous drug. Follow applicable special handling and disposal procedures.
8PRINCIPAL DISPLAY PANEL - 0.9 mg Vial Label
Pfizer
NDC 0008-0100-01
BESPONSA™
(inotuzumab ozogamicin)
for Injection
(inotuzumab ozogamicin)
for Injection
0.9 mg/vial
For Intravenous Infusion Only
No Preservatives
Single-dose vial.
Discard unused portion.
Discard unused portion.
9PRINCIPAL DISPLAY PANEL - 0.9 mg Vial Carton
Pfizer
NDC 0008-0100-01
BESPONSA™(inotuzumab ozogamicin)
for Injection
for Injection
0.9 mg/vial
For Intravenous Infusion Only
Reconstitution and dilution
No Preservatives
One Single-Dose Vial.
Rx only
