Imbruvica-Rituximab Combo Approved by FDA for Chronic Lymphocytic Leukemia


The U.S. Food and Drug Administration (FDA) approved Janssen Pharmaceutical of Johnson & Johnson’s Imbruvica (ibrutinib) in combination with Genentech and Biogen’s Rituxan (rituximab) for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients who are new to therapy.

Imbruvica is a once-daily, first-in-class Bruton’s tyrosine kinase (BTK) inhibitor. It was jointly developed and commercialized by Janssen Biotech and Pharmacyclics, an AbbVie company. Rituximab is approved for non-Hodgkin’s Lymphoma (NHL) alone or with chemotherapy, and CLL with chemotherapy drugs fludarabine and cyclophosphamide. Rituximab is an antibody targeting the CD20 protein.

The approval was built on the Phase III E1912 trial designed and run by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and sponsored by the National Cancer Institute (NCI). This is the 11th FDA approval for Imbruvica across six disease areas and the sixth for the drug in CLL.

The E1912 trial demonstrated that newly diagnosed patients ages 70 years or younger receiving the drug plus rituximab lived longer without disease progression, with a progression-free survival (PFS) of 88% at 37 months compared to patients receiving fludarabine, cyclophosphamide and rituximab (FCR), with a PFS of 75%.

“FCR, a chemoimmunotherapy-based regimen, has been the standard of care for many previously untreated younger patients with CLL,” said Brian Koffman, co-founder and chief medical officer and executive vice president of the CLL Society. “With the introduction of this ibrutinib-rituximab combination, patients now have a more effective, non-chemoimmunotherapy option. In the 14 years since I was first diagnosed with CLL, the treatment landscape has advanced dramatically for the better, with ibrutinib continuing to play a pioneering role in defining what it means to live with this disease.”

The application was approved via the FDA’s Real-Time Oncology Review (RTOR) pilot program. It also had Priority Review designations. It was also approved under a modified version of Project Orbis, a multinational partnership between the FDA, the Australian Therapeutic Goods Administration (TGA), Health Canada, Health Sciences Authority (HSA, Singapore) and Swissmedic (SMC, Switzerland).

“The FDA’s Project Orbis provides a framework for concurrent submission and review of oncology drug applications among the FDA’s international collaborators,” stated Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

The E1912 study evaluated 529 previously untreated CLL patients who were 70 years of age or younger. They were randomized to receive either Imbruvica plus rituximab or the chemoimmunotherapy FCR regimen. The median follow-up time for the study was 37 months.

“We commend the ECOG-ACRIN Cancer Research Group and the National Cancer Institute for conducting a robust study that has generated insightful and landmark results in the treatment of CLL,” said Craig Tendler, vice president, clinical development and global medical affairs, Oncology, Janssen Research & Development. “We are committed to the continued study of Imbruvica-based regimens and building upon the efficacy and safety of the most comprehensively studied BTK inhibitor in our efforts to improve the lives of patients facing a blood cancer diagnosis.”

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