Drugs Xagena
The European Commission ( EC ) has approved Mylotarg ( Gemtuzumab ozogamicin ) in combination with Daunorubicin and Cytarabine for the treatment of patients age 15 years and above with previously untreated, de novo, CD33-positive acute myeloid leukemia ( AML ), except acute promyelocytic leukemia ( APL ).
Mylotarg is the first acute myeloid leukemia therapy approved in the European Union ( EU ) that targets CD33, an antigen expressed on AML cells in up to 90% of patients.
Acute myeloid leukemia is a rapidly progressing, life-threatening blood and bone marrow cancer. If left untreated, patients with acute myeloid leukemia will die within months, if not weeks, of their disease. Acute myeloid leukemia is the most common type of acute leukemia in adults and accounts for approximately 80% of all cases of acute leukemia.
About 16,800 people are expected to be newly diagnosed with acute myeloid leukemia in Europe annually.
The goal of acute myeloid leukemia treatment is for the patient to achieve a complete, prolonged remission. Longer periods of remission prior to relapse are associated with better long-term outcomes for patients. Thus, medicines that delay the time until the disease comes back and extend life can provide meaningful clinical benefit.
The European Commission’s approval of Mylotarg was based on data from an investigator-led, phase 3 randomized, open-label study ( ALFA-0701 ) in previously untreated, de novo patients.
Mylotarg received approval by the U.S. Food and Drug Administration( FDA ) in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia, and adults and children 2 years and older with relapsed or refractory CD33-positive acute myeloid leukemia.
Mylotarg is approved in combination with Daunorubicin and Cytarabine for the treatment of patients age 15 and above with previously untreated, de novo, CD33-positive acute myeloid leukemia, except acute promyelocytic leukemia.
The overall safety profile of Mylotarg is based on data from patients with acute myeloid leukemia from the combination therapy study ALFA-0701, monotherapy studies, and from post-marketing experience.
Hepatotoxicity, including life-threatening, and sometimes fatal hepatic failure and hepatic veno-occlusive disease ( VOD ) or sinusoidal obstruction syndrome ( SOS ) have been reported in patients treated with Mylotarg.
Other special warnings and precautions include myelosuppression and infusion-related reactions.
In the combination therapy study ALFA-0701, clinically relevant serious adverse reactions were hepatotoxicity, including hepatic veno-occlusive disease or sinusoidal obstruction syndrome ( 3.8% ), hemorrhage ( 9.9% ), severe infection ( 41.2% ), and tumour lysis syndrome ( 1.5% ).
In monotherapy studies, clinically relevant serious adverse reactions have also included infusion related reactions ( 2.5% ), thrombocytopenia ( 21.7% ), and neutropenia ( 34.3% ).
The most common adverse reactions ( more than 30% ) in the combination therapy study were hemorrhage and infection.
In monotherapy studies the most common adverse reactions ( more than 30% ) have included pyrexia, nausea, infection, chills, hemorrhage, vomiting, thrombocytopenia, fatigue, headache, stomatitis, diarrhea, abdominal pain, and neutropenia.
The most frequent ( 1% or more ) adverse reactions that led to permanent discontinuation in the combination therapy study were thrombocytopenia, hepatic veno-occlusive disease, hemorrhage and infection. The most frequent ( 1% or more ) adverse reactions that led to permanent discontinuation in monotherapy studies were infection, hemorrhage, multi-organ failure, and hepatic veno-occlusive disease.
Gemtuzumab ozogamicin is an antibody-drug conjugate ( ADC ) composed of the cytotoxic agent Calicheamicin, attached to a monoclonal antibody ( mAB ) targeting CD33, an antigen expressed on the surface of myeloblasts in up to 90% of patients with acute myeloid leukemia.
When Gemtuzumab ozogamicin binds to the CD33 antigen on the cell surface it is absorbed into the cell and Calicheamicin is released causing cell death. ( Xagena )
Source: Pfizer, 2018
XagenaMedicine_2018
