FDA Approves Ibrutinib for Mantle Cell Lymphoma

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Richard Pazdur, MD

The U.S. Food and Drug Administration has approved ibrutinib (Imbruvica) to treat patients with mantle cell lymphoma, a rare and aggressive form of non-Hodgkin lymphoma representing about 6% of all non-Hodgkin lymphoma cases in the United States. By the time mantle cell lymphoma is diagnosed, it usually has already spread to the lymph nodes, bone marrow, and other organs.

Ibrutinib is intended for patients with mantle cell lymphoma who have received at least one prior therapy. It works by inhibiting the enzyme needed by the cancer to multiply and spread. Ibrutinib is the third drug approved to treat mantle cell lymphoma, following the 2006 approval of bortezomib (Velcade) and lenalidomide (Revlimid) to treat the disease.

Breakthrough Therapy Designation

“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The agency worked cooperatively with the companies to expedite the drug’s development, review, and approval, reflecting the promise of the Breakthrough Therapy Designation program,” Dr. Pazdur said.

Imbruvica is the second drug with breakthrough therapy designation to receive FDA approval. The Food and Drug Administration Safety and Innovation Act, passed in July 2012, gave the FDA the ability to designate a drug a breakthrough therapy at the request of the sponsor if preliminary clinical evidence indicates the drug may offer a substantial improvement over available therapies for patients with serious or life-threatening diseases.

Accelerated Approval

The FDA has approved ibrutinib under the agency’s accelerated approval program, which allows the FDA to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. The FDA also granted ibrutinib priority review because the drug demonstrated the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition and orphan-product designation because the drug is intended to treat a rare disease.

Clinical Efficacy and Side Effect Profile

Ibrutinib’s accelerated approval for mantle cell lymphoma is based on a study where 111 participants were given ibrutinib daily until their disease progressed or side effects became intolerable. Results showed an overall response rate of nearly 66%. An improvement in survival or disease-related symptoms has not been established. The most common side effects reported in participants receiving ibrutinib are thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, edema, upper respiratory infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting, and decreased appetite. Other clinically significant side effects include bleeding, infections, kidney problems and the development of other types of cancers. ■

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