Inotuzumab ozogamicin
Humanized (from mouse) | |
Target | CD22 |
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Clinical data | |
Trade names | Besponsa |
Other names | CMC-544 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a617041 |
License data | |
Pregnancy category |
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Intravenous | |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Protein binding | 97% (cytotoxic agent) |
Elimination half-life | 12.3 days |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
KEGG | |
Chemical and physical data | |
Formula | C6518H10002N1738O2036S42 |
Molar mass | 146634.36 g·mol−1 |
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Inotuzumab ozogamicin, sold under the brand name Besponsa, is an
The medication consists of a
The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[6]
Medical use
Inotuzumab ozogamicin is used to treat relapsed or refractory B-cell precursor acute lymphoblastic leukemia.[3][4]
In March 2024, the FDA approved inotuzumab ozogamicin for the treatment of children aged one year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.[7]
Adverse effects
The FDA label for the use of inotuzumab ozagamicin carries a
The most common serious adverse reactions in people taking the drug in the clinical trial leading to approval were infections (23%), loss of neutrophils with fever (11%), hemorrhage (5%), stomach pain (3%), fever (3%), VOD (2%), and tiredness (2%).[3]
More than 20% of people had the following adverse reactions: loss of platelets (51%), loss of neutrophils (49%), infections (48%), anemia (36%), leukopenia (35%), tiredness (35%), hemorrhage (33%), fever (32%), nausea (31%), headache (28%), loss of neutrophils with fever (26%), elevated transaminases (26%), stomach pain (23%), and jaundice (21%).[citation needed]
Between 10% and 20% of people also had loss of appetite, vomiting, diarrhea, mouth sores, constipation, chills, and injection site reactions.[3]
In studies in pregnant animals, the drug caused harm to the fetus at doses less than those used clinically, and so the drug has not been tested in pregnant women.[3]
Pharmacology
The antibody component of inotuzumab ozogamicin binds to
Chemistry
Inotuzumab ozogamicin consists of the
History
Inotuzumab ozogamicin was discovered by scientists collaborating at Celltech and Wyeth, and it was developed by Pfizer which had acquired Wyeth. Celltech and Wyeth entered into a collaboration in 1991 to develop antibody-drug conjugates.[14]
The humanized antibody portion was generated at Celltech and the DNA encoding it was transfected into CHO cells, which were sent to Wyeth, where chemists expressed and purified the antibodies and conjugated them with the linker to the cytotoxin; the work was published in 2004.[13] Celltech was acquired by UCB in 2004[15] and Wyeth was acquired by Pfizer in 2009.[16]
In May 2013, a phase III trial in patients with relapsed or refractory CD22+ aggressive non-Hodgkin lymphoma (NHL) who were not candidates for intensive high-dose chemotherapy was terminated for futility.[17]
In March 2024, the FDA approved inotuzumab ozogamicin for the treatment of children aged one year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.[7] Efficacy was evaluated in a multicenter, single-arm, open-label study in 53 pediatric participants aged one year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia.[7] Two dose levels were evaluated--an initial dose of 1.4 mg/m2/cycle in 12 participants and 1.8 mg/m2/cycle in 41 participants.[7] Premedications included methylprednisolone 1 mg/kg (maximum of 50 mg), an antipyretic, and an antihistamine.[7] Participants received a median of 2 cycles of therapy (range: 1 to 4 cycles).[7] The application was granted priority review and orphan drug designations.[7]
Society and culture
Legal status
In 2017, inotuzumab ozogamicin was approved by the European Commission and the FDA for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia under the brand name Besponsa (Pfizer/Wyeth).[3][4]
References
- FDA. Retrieved 22 October 2023.
- ^ "Search Page - Drug and Health Product Register". 23 October 2014.
- ^ a b c d e f g h i j "Besponsa 1 mg powder for concentrate for solution for infusion". UK Electronic Medicines Compendium. June 2017. Retrieved 19 August 2017.
- ^ a b c d e f "Besponsa- inotuzumab ozogamicin injection, powder, lyophilized, for solution". DailyMed. 15 September 2020. Retrieved 16 November 2020.
- ^ PMID 22003069.
- ^ New Drug Therapy Approvals 2017 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2018. Retrieved 16 September 2020.
- ^ a b c d e f g "FDA approves inotuzumab ozogamicin for pediatric patients with acute lymphoblastic leukemia". U.S. Food and Drug Administration. 6 March 2024. Retrieved 9 March 2024. This article incorporates text from this source, which is in the public domain.
- S2CID 242875059. Retrieved 21 August 2023.
- ^ "Inotuzumab ozogamicin (CMC-544)". ADC Review. 20 February 2016.
- ^ "Recommended INN: List 54" (PDF). WHO Drug Information. 19 (3). 2005.
- PMID 12901947.
- PMID 11792178.
- ^ PMID 14615373.
- ^ "Inotuzumab Ozogamicin". Informa Biomedtracker. Archived from the original on 19 August 2017. Retrieved 19 August 2017.
- ^ "Celltech sold to Belgian firm in £1.5bn deal". The Guardian. 18 May 2004.
- ^ Sorkin AR, Wilson D (25 January 2009). "Pfizer Agrees to Pay $68 Billion for Rival Drug Maker Wyeth". The New York Times.
- ^ "Pfizer Discontinues Phase 3 Study of Inotuzumab Ozogamicin in Relapsed or Refractory Aggressive Non-Hodgkin Lymphoma (NHL) Due to Futility. May 2013". Archived from the original on 8 August 2014. Retrieved 20 July 2014.
External links
- "Inotuzumab Ozogamicin". National Cancer Institute. September 2017.
- "Inotuzumab Ozogamicin". NCI Drug Dictionary. National Cancer Institute.