The FINANCIAL -- Pfizer Inc. on April 23 announced that the European Commission 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 and only AML therapy approved in the European Union (EU) that targets CD33, an antigen expressed on AML cells in up to 90% of patients.
“The marketing authorization of MYLOTARG provides a much-needed treatment option offering renewed hope for many acute myeloid leukemia patients in Europe,” said Andreas Penk, M.D., regional president, Pfizer Oncology. “In clinical trials, the addition of MYLOTARG to standard chemotherapy resulted in deeper, more durable remission, thus providing an additional treatment option with the potential to prevent relapse for these patients.”
AML is a rapidly progressing, life-threatening blood and bone marrow cancer. If left untreated, patients with AML will die within months, if not weeks, of their disease. AML 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 AML in Europe annually. The goal of AML 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, according to Pfizer.
“I am thrilled that MYLOTARG will be available soon in Europe as a first-line treatment for patients with acute myeloid leukemia,” said Doctor Sylvie Castaigne, Professeur des Universités, Université de Versailles - Saint Quentin, Praticien Hospitalier, Centre Hospitalier de Versailles, and lead investigator of the ALFA-0701 study. “This important milestone is a result of close collaboration between Pfizer and clinical investigators around the world, particularly the ALFA investigators in France, who believed in the promise of this therapy. We thank all of the investigators, nurses and patients who participated in these studies.”
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 in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children 2 years and older with relapsed or refractory CD33-positive AML.
Pfizer is advancing a broad range of therapies that leverage multiple pathways and mechanisms of action (MOAs) to address acute and chronic leukemias, myeloproliferative disorders and lymphomas. Pfizer currently has four marketed therapies for hematologic cancers worldwide as well as several therapies in clinical development. Pfizer is also forging collaborations with a diversity of industry, academic and community partners to study multiple paths to advancing treatment. By working together, Pfizer and its partners aim to overcome the challenges of hematologic cancers and deliver meaningful benefits to patients.
Indication for MYLOTARG (gemtuzumab ozogamicin) in the EU
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 (AML), except acute promyelocytic leukemia (APL).
IMPORTANT MYLOTARG (gemtuzumab ozogamicin) SAFETY INFORMATION in the EU
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 VOD/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 VOD/SOS (3.8%), hemorrhage (9.9%), severe infection (41.2%), and tumour lysis syndrome (1.5%). In monotherapy studies, clinically relevant serious adverse reactions also included infusion related reactions (2.5%), thrombocytopenia (21.7%), and neutropenia (34.3%).
The most common adverse reactions (> 30%) in the combination therapy study were hemorrhage and infection. In monotherapy studies the most common adverse reactions (> 30%) included pyrexia, nausea, infection, chills, hemorrhage, vomiting, thrombocytopenia, fatigue, headache, stomatitis, diarrhea, abdominal pain, and neutropenia.
The most frequent (≥ 1%) adverse reactions that led to permanent discontinuation in the combination therapy study were thrombocytopenia, VOD, hemorrhage and infection. The most frequent (≥ 1%) adverse reactions that led to permanent discontinuation in monotherapy studies were infection, hemorrhage, multi-organ failure, and VOD.
About MYLOTARG (gemtuzumab ozogamicin)
MYLOTARG 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 percent of AML patients. When MYLOTARG binds to the CD33 antigen on the cell surface it is absorbed into the cell and calicheamicin is released causing cell death.
MYLOTARG was approved by the U.S. Food and Drug Administration in September 2017 for adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), and adults and children 2 years and older with relapsed or refractory CD33-positive AML.
MYLOTARG originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development and commercialization activities for this molecule.
Pfizer also collaborated with SFJ Pharmaceuticals Group on the registrational program for MYLOTARG.