Glucarpidase, an intravenously delivered recombinant enzyme, was approved on Jan. 17 for the treatment of patients with toxic levels of methotrexate in their blood due to kidney failure, according to the Food and Drug Administration.
Patients receiving high doses of methotrexate can develop renal failure, which allows the chemotherapy drug to accumulate. Glucarpidase (Voraxaze) rapidly breaks down methotrexate into a form that can then be eliminated from the body, according to the agency.
In addition to kidney failure, prolonged exposure to high levels of methotrexate can result in "liver damage, severe mouth sores, damage to the lining of the intestine, skin rashes, and death due to low blood counts," Dr. Richard Pazdur, director of the FDA’s Office of Hematology and Oncology Products, said in a statement. "Voraxaze is an important new treatment option for cancer patients aimed at preventing these toxicities associated with sustained high levels of methotrexate," he added.
According to glucarpidase’s manufacturer, BTG Plc, high-dose methotrexate is used to treat or prevent the recurrence of certain types of cancer, such as osteosarcoma, leukemia, and lymphoma.
Methotrexate also is used to treat rheumatologic conditions, such as rheumatoid arthritis.
The enzyme had been available to some patients under the FDA’s investigational new drug designation. In 2008, Protherics Inc., which previously owned the rights to glucarpidase, was warned by the FDA against promoting the drug before it was approved.
Glucarpidase received orphan drug status, which put it on a priority review track.
Approval was based on two studies: a single clinical study of 22 patients that evaluated effectiveness and a 290-patient trial that evaluated safety.
According to the FDA, treatment was considered successful if methotrexate levels fell below a critical level within 15 minutes and stayed below the critical level for 8 days. That result was seen in 10 of the 22 patients. BTG said that there was a 95% reduction in methotrexate concentration from pretreatment baseline levels, maintained for up to 8 days, in all evaluable patients.
The most common side effects were hypotension, headache, nausea, vomiting, flushing, and paraesthesia.
Louise Makin, chief executive officer of BTG, said in a statement that glucarpidase "is the first product BTG has taken through to approval in the U.S. and we look forward to its launch over coming months."