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FDA approves Imbruvica for mantle cell lymphoma
The FDA today approved ibrutinib for treatment of patients with mantle cell lymphoma who have received at least one prior therapy.
Ibrutinib (Imbruvica, Pharmacyclics and Janssen) — a Bruton’s tyrosine kinase inhibitor — is the third drug approved to treat mantle cell lymphoma, following bortezomib (Velcade, Millennium Pharmaceuticals) and lenalidomide (Revlimid, Celgene).
As a rare form of non-Hodgkin’s lymphoma, mantle cell lymphoma represents about 6% of all NHL cases in the United States. However, by the time of its detection, mantle cell lymphoma has often already spread to the lymph nodes, bone marrow and other organs.
Richard Pazdur
“Imbruvica’s approval demonstrates the FDA’s commitment to making treatments available to patients with rare diseases,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research, said in a press release. “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.”
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.
The FDA granted ibrutinib priority review due to the drug’s demonstrated potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition. Ibrutinib also received orphan-product designation because it is intended to treat a rare disease.
Ibrutinib’s accelerated approval for mantle cell lymphoma is based on a study in which 111 patients with relapsed or refractory mantle cell lymphoma received ibrutinib 560 mg daily. Results indicated that nearly 66% of patients exhibited tumor shrinkage or eradication after treatment. However, an improvement in survival or disease-related symptoms has not been established.
The most common reported adverse events included 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 adverse events included bleeding, infections, kidney problems and the development of other types of cancers.
Perspective
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Ibrutinib is an exciting drug that shows promise in the treatment of several types of lymphoma, including mantle cell lymphoma. The compound has also demonstrated high response rates in chronic lymphocytic leukemia that has relapsed after standard therapy.
The development of ibrutinib progressed quickly as a result of a strong partnership between Pharmacyclics, academic medicine and the FDA. The FDA has bent over backwards to make the drug available to patients at a record pace. Ibrutinib started clinical trials in 2009. It’s 2013, and patients now have access to it.
Ibrutinib is going to have tremendous impact. It’s an oral, well-tolerated, patient-friendly therapy that has demonstrated extremely high rates of response and induces durable remissions.
In CLL, for example, remission is 75% at 2 or more years, whereas with standard therapy, the average patient would have progressed in 14 months or less.
At present, first-line therapy for CLL is chemoimmunotherapy. When patients fail that therapy or the disease returns, particularly in elderly patients, we don’t have good alternative treatments that produce durable remissions without significant side effects. On this front, ibrutinib works well to bring the disease under control and relieve symptoms of the disease.
The next step for ibrutinib is likely to be in earlier treatment for CLL. It has the potential to replace chemotherapy in this regard. Initial studies of ibrutinib as first-line therapy for CLL demonstrate very high response. In pilot studies, the remission is extremely durable. Pharmacyclics will need more information, and the company is testing ibrutinib in untreated CLL as part of a registration strategy.