Besponsa (Inotuzumab Ozogamicin)

Introduction 

Inotuzumab ozogamicin, sold under the brand name Besponsa, is an antibody-drug conjugate medication which the doctors use to treat relapsed or refractory B-cell precursor acute lymphoblastic leukaemia (ALL). In fact, the medication consists of a humanized monoclonal antibody against CD22 (inotuzumab), linked to a cytotoxic agent from the class of calicheamicins called ozogamicin. Experts use Inotuzumab ozogamicin in order to treat relapsed or refractory B-cell precursor acute lymphoblastic leukaemia. 

Scientists collaborating at Celltech and Wyeth, discovered this drug; and Pfizer which had acquired Wyeth developed it eventually. In fact, the US Food and Drug Administration (FDA) considers it to be a first-in-class medication. In 2017, European Commission and also the FDA approved inotuzumab ozogamicin for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukaemia (ALL) in 2017 under the trade name Besponsa. 

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. Pregnant women should not take inotuzumab ozogamicin and must not become pregnant while taking it. It is unknown if the drug or its metabolites secretes in breast milk, but women should not breastfeed while taking it and should wait two months after the last dose to start breastfeeding. 

Inotuzumab ozogamicin has an approximate molecular weight of 160 kDa. Therefore, the average number of calicheamicin derivative molecules conjugated to each inotuzumab molecule is approximately 6 with a distribution from 2-8. The chemical conjugation of the antibody and also the small molecule components produces Inotuzumab ozogamicin. Mammalian cells produces the antibody; and the Microbial fermentation followed by synthetic modification, produces the semisynthetic calicheamicin derivative. 

The antibody component of inotuzumab ozogamicin binds to CD22 receptors, which are, in fact, expressed mostly on B cells. The whole conjugate is then drawn into the cell, where the ozogamicin is cleaved from the antibody by the acidic environment of the lysosome. The ozogamicin eventually travels to the nucleus where it breaks up DNA, causing the cell to die. 

How should this medicine be used?

Inotuzumab ozogamicin injection comes as a powder to be mixed with liquid to be injected intravenously (into a vein) by a doctor or nurse in a hospital or medical facility. However, experts usually inject it on days 1, 8, and 15 of a 3- to 4-week cycle. A patient may repeat this cycle every 4 weeks as per the recommendation by your doctor. In fact, the length of your treatment depends on how well your body responds to the medication and the side effects that you experience.

Your doctor may need to interrupt or stop your treatment, lower your dose, or treat you with additional medications, depending on your response to inotuzumab ozogamicin and any side effects that you experience. You will receive certain medications to help prevent a reaction before you receive each dose of inotuzumab ozogamicin. Talk to your doctor about how you are feeling during and after your treatment.

Side effects:

Common side effects of Besponsa include:

  • low platelet counts (thrombocytopenia)   
  • low white blood cell counts
  • Infection
  • anaemia
  • fatigue
  • bleeding
  • fever
  • nausea
  • headache
  • febrile neutropenia
  • transaminases increased
  • abdominal pain and diarrhoea
  • constipation
  • vomiting
  • swelling and sores inside the mouth
  • Chills
  • gamma-glutamyltransferase increased
  • too much bilirubin in the blood

If you experience any of these symptoms call your doctor immediately or get emergency medical treatment:

  • fever, chills, cough, or other signs of infection
  • unusual bleeding or bruising
  • black and tarry stools
  • red blood in stools
  • pale skin
  • fatigue