FDA Approves Imbruvica (ibrutinib) for Chronic Graft Versus Host Disease

The U.S. Food and Drug Administration today expanded the approval of Imbruvica (ibrutinib) for the treatment of adult patients with chronic graft versus host disease (cGVHD) after failure of one or more treatments. This is the first FDA-approved therapy for the treatment of cGVHD.

cGVHD is a life-threatening condition that can occur in patients after they receive a stem cell transplant from blood or bone marrow, called hematopoietic stem cell transplantation (HSCT), to treat certain blood or bone marrow cancers. cGVHD occurs when cells from the stem cell transplant attack healthy cells in a patient’s tissues. Symptoms of cGVHD can occur in the skin, eyes, mouth, gut, liver and lungs. The condition is estimated to occur in 30-70 percent of all patients who receive HSCT.

"Patients with cGVHD who do not respond to other forms of therapy—typically corticosteroids to suppress their immune system—now have a treatment option specifically indicated to treat their condition," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "This approval highlights how a known treatment for cancer is finding a new use in treating a serious and life-threatening condition that may occur in patients with blood cancer who receive a stem cell transplant."

The efficacy and safety of Imbruvica for the treatment of cGVHD were studied in a single-arm trial of 42 patients with cGVHD whose symptoms persisted despite standard treatment with corticosteroids. Most patients’ symptoms included mouth ulcers and skin rashes, and more than 50 percent of patients had two or more organs affected by cGVHD. In the trial, 67 percent of patients experienced improvements in their cGVHD symptoms. In 48 percent of patients in the trial, the improvement of symptoms lasted for up to five months or longer.

Common side effects of Imbruvica in patients with cGVHD include fatigue, bruising, diarrhea, low levels of blood platelets (thrombocytopenia), muscle spasms, swelling and sores in the mouth (stomatitis), nausea, severe bleeding (hemorrhage), low levels of red blood cells (anemia) and lung infection (pneumonia).

Serious side effects of Imbruvica include severe bleeding (hemorrhage), infections, low levels of blood cells (cytopenias), irregular heartbeat (atrial fibrillation), high blood pressure (hypertension), new cancers (second primary malignancies) and metabolic abnormalities (tumor lysis syndrome). Women who are pregnant or breastfeeding should not take Imbruvica because it may cause harm to a developing fetus or a newborn baby.

Imbruvica, a kinase inhibitor, was previously approved for certain indications in treating chronic lymphocytic leukemia, Waldenström’s macroglobulinemia and marginal zone lymphoma, as well as under accelerated approval status for mantle cell lymphoma.

The FDA granted this application Priority Review and Breakthrough Therapy designations. Imbruvica also received Orphan Drug designation for this indication, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted the approval of Imbruvica to Pharmacyclics LLC.