FDA Clears Pfizer’s ADC for Leukemia

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Pfizer’s Mylotarg, an anti-body drug conjugate once voluntarily withdrawn, returns to the market under a new dosing regimen for treating leukemia.

On Sep. 1, 2017, FDA approved Pfizer’s Mylotarg (gemtuzumab ozogamicin), an antibody drug-conjugate (ADC) for treating acute myeloid leukemia (AML) in adults and pediatric patients aged 2 years and older. The drug is specifically indicated to treat AML in patients who are CD33-positive, that is, whose tumors express the CD33 antigen.

Mylotarg was originally approved by FDA under accelerated review in May 2000 as a stand-alone treatment for older patients with CD33-positive AML, but Pfizer voluntarily withdrew the drug from the market in 2010 after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths. The drug remained on the market in Japan, however, and has been available to individual patients through Pfizer’s compassionate-use programs.  The current 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 Mylotarg after a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk,” said Richard Pazdur, MD, director of FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in FDA’s Center for Drug Evaluation and Research, in an agency press release. “Mylotarg’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.”

As an ADC, Mylotarg is a targeted therapy that consists of an antibody connected to the cytotoxic agent, calicheamicin. It is thought to work by taking the anti-tumor agent to the AML cells that express the CD33 antigen, blocking the growth of cancerous cells and causing cell death, according to FDA. The drug originates from a collaboration between Pfizer and Celltech, now UCB, a Belgian biopharmaceutical company. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.

Pfizer’s Drug Joins Other ADCs in the Market


Mylotarg marks the third ADC approved for marketing in the United States. The other two ADCs approved in the US are Seattle Genetics’ Adcetris (brentuximab vedotin), for treating classical Hodgkin lymphoma and systemic anaplastic large cell lymphoma, and Roche’s Kadcyla (trastuzumab emtansine), for treating HER2-positive, metastatic breast cancer.

Seattle Genetics, a biotechnology company in Bothell, Washington, developed Adcetris in collaboration with Takeda Pharmaceutical. Adcetris, approved by FDA in 2011, had 2016 sales of $265.8 million and is commercially available in 65 countries, including the US, Canada, Japan, and members of the European Union (EU).

Roche licenses technology for Kadcyla under an agreement with ImmunoGen, a Waltham, Massachusetts-based clinical-stage biotechnology company that uses its proprietary ADC technology to develop targeted cancer therapeutics. Kadcyla, approved by FDA in 2013, had 2016 sales of CHF 831 million (US$869 million). It was also approved in the EU in 2013.

Source: FDA, Pfizer