sNDA Submitted for Ibrutinib in Combination with Rituximab for Treatment of WM

The FDA is set to review a supplemental new drug application for ibrutinib in combination with rituximab for the treatment of Waldenström’s macroglobulinemia.

The FDA is set to review a supplemental new drug application for ibrutinib (Imbruvica) in combination with rituximab (Rituxan) for the treatment of Waldenström’s macroglobulinemia (WM), according to Abbvie, the developer of the agent.

The application is seeking to update the US prescribing information for ibrutinib based on more than 5 years of data reported from the phase 3 iNNOVATE clinical trial.

"Since [ibrutinib] became the first FDA-approved medicine to treat people living with Waldenström's macroglobulinemia more than 5 years ago, it has significantly changed the treatment landscape for this rare and incurable form of non-Hodgkin's lymphoma," Danelle James, MD, MAS, ibrutinib global development lead at Pharmacyclics LLC, an AbbVie company. "This latest submission reinforces how [ibrutinib] has provided an innovative treatment option for WM patients and our commitment to supporting this patient community."

In the randomized, placebo-controlled, double-blind, phase 3 study, 150 patients with relapsed or refractory and treatment-naïve WM were enrolled. Participants were randomized to receive intravenous rituximab 375 mg/m2 once weekly for 4 consecutive weeks, followed by a second 4-weekly rituximab course following a 3-month interval. All patients were given either 420 mg of ibrutinib or placebo once daily continuously until the criteria for treatment discontinuation were met.

The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), hematological improvement measured by hemoglobin, time-to-next treatment, overall survival (OS), and number of participants with adverse events (AEs) as a measure of safety and tolerability within each treatment arm.

Results from the long-term analysis of the Phase 3 iNNOVATE study will be presented at a future medical congress.

"We've made significant progress in the treatment of Waldenström's macroglobulinemia, which until a couple years ago had limited treatment options including chemotherapy," principle investigator Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Athens, Greece, said in a press release. "The iNNOVATE study continues to deliver strong clinical evidence supporting the long-term use of ibrutinib plus rituximab across first and second lines of therapy for patients with Waldenström's macroglobulinemia."

WM is a rare and incurable form of non-Hodgkin’s lymphoma. Typically, WM affects older adults and is generally found in the bone marrow, though the lymph nodes and spleen have been known to be affected as well. In the US, it is estimated that there are about 2800 new cases of WM each year.

Ibrutinib was first approved as a single agent, oral therapy for all lines of WM in 2015, making it the first and only FDA-approved medicine for WM. In 2018, ibrutinib was also approved as the first chemotherapy-free combination treatment with rituximab.

As of today, ibrutinib is still the only Bruton's tyrosine kinase (BTK) inhibitor approved to treat WM. As of May 2020, the National Comprehensive Cancer Network (NCCN) recommends ibrutinib with or without rituximab as the preferred regimen for patients with WM.


IMBRUVICA® (ibrutinib) Seeks to Expand U.S. Label with Long-Term Data in Waldenström's Macroglobulinemia (WM) [news release]. North Chicago, Illinois. Published June 23, 2020. Accessed June 23, 2020.