The U.S. Food and Drug Administration has approved gemtuzumab ozogamicin for the treatment of adults with newly diagnosed acute myeloid leukaemia whose tumours express the CD33 antigen (CD33-positive AML).

The FDA also approved gemtuzumab ozogamicin for the treatment of patients aged 2 years and older with CD33-positive AML who have experienced a relapse or who have not responded to initial treatment (refractory).

Gemtuzumab ozogamicin originally received accelerated approval in May 2000 as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse.

Gemtuzumab ozogamicin was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths.

Today’s approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population.

“We are approving gemtuzumab ozogamicin after a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Haematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It’s history underscores the importance of examining alternative dosing, scheduling, and administration of therapies for patients with cancer, especially in those who may be most vulnerable to the side effects of treatment.”

AML is a rapidly progressing cancer that forms in the bone marrow and results in an increased number of white blood cells in the bloodstream.

The National Cancer Institute of the National Institutes of Health estimates that approximately 21,380 people will be diagnosed with AML this year and that 10,590 patients with AML will die of the disease.

Gemtuzumab ozogamicin is a targeted therapy that consists of an antibody connected to an anti-tumour agent that is toxic to cells.

It is thought to work by taking the anti-tumour agent to the AML cells that express the CD33 antigen, blocking the growth of cancerous cells and causing cell death.

The safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for adults were studied in a trial of 271 patients with newly diagnosed CD33-positive AML who were randomized to receive gemtuzumab ozogamicin in combination with daunorubicin and cytarabine or to receive daunorubicin and cytarabine without gemtuzumab ozogamicin.

The trial measured “event-free survival,” or how long patients went without certain complications, including failure to respond to treatment, disease relapse or death, from the date they started the trial. 

Patients who received gemtuzumab ozogamicin in combination with chemotherapy went longer without complications than those who received chemotherapy alone (median, event-free survival 17.3 months vs. 9.5 months).

The safety and efficacy as a stand-alone treatment were studied in two, separate trials.

The first trial included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy.

Patients were randomised to receive treatment with gemtuzumab ozogamicin or best supportive care.

The trial measured “overall survival,” or how long patients survived from the date they started the trial.

Patients who received gemtuzumab ozogamicin survived longer than those who received only best supportive care (median overall survival 4.9 months vs. 3.6 months).

The second trial was a single-arm study that included 57 patients with CD33-positive AML who had experienced one relapse of disease.

Patients received a single course of gemtuzumab ozogamicin.

The trial measured how many patients achieved a complete remission.

Following treatment, 26 percent of patients achieved a complete remission that lasted a median 11.6 months.

Common side effects include fever (pyrexia), nausea, infection, vomiting, bleeding, low levels of platelets in the blood (thrombocytopenia), swelling and sores in the mouth (stomatitis), constipation, rash, headache, elevated liver function tests, and low levels of certain white blood cells (neutropenia).

Severe side effects include low blood counts, infections, liver damage, blockage of the veins in the liver (hepatic veno-occlusive disease), infusion-related reactions, and severe bleeding (haemorrhage).

Women who are pregnant or breastfeeding should not take gemtuzumab ozogamicin, because it may cause harm to a developing foetus or a newborn baby.

Patients with hypersensitivity to gemtuzumab ozogamicin or any component of its formulation should not use gemtuzumab ozogamicin.

The prescribing information for gemtuzumab ozogamicin includes a boxed warning that severe or fatal liver damage (hepatotoxicity), including blockage of veins in the liver (veno-occlusive disease or sinusoidal obstruction syndrome), occurred in some patients who took gemtuzumab ozogamicin.

Gemtuzumab ozogamicin received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

Source: FDA