Long-term data showed that the addition of Imbruvica did not improve overall survival in patients with marginal zone lymphoma or mantle cell lymphoma.
The pharmaceutical companies developing Imbruvica (ibrutinib) intend to voluntarily withdraw the drug’s indication for the treatment of patients with previously treated mantle cell lymphoma who have received at least one prior therapy and patients with marginal zone lymphoma who require systemic therapy and have received at least one anti-CD20-based treatment, according to a statement from Janssen.
Both indications were granted accelerated approvals, which mean that the continued approval would be contingent upon further research that confirms their benefit. However, when representatives from the drug makers (Janssen, Pharmacyclics and AbbVie) met with the Food and Drug Administration (FDA) to discuss findings from the phase 3 confirmatory trials, SHINE and SELENE, the FDA explained that the data were not sufficient to support a full approval.
The phase 3 SHINE trial, which compared a combination of Imbruvica, Rituxan (rituximab) and Bendeka (bendamustine) to placebo, Rituxan and Bendeka in patients with mantle cell lymphoma found that the Imbruvica-containing arm improved time from treatment until the disease spread or worsened (a statistic known as progression-free survival), but did not have an overall survival benefit, meaning that there was not a significant difference in the average time a patient lived after receiving the treatment.
Adding Imbruvica to the treatment regimen also resulted in additional side effects. According to data from the SHINE trial which were presented at the 2022 American Society of Clinical Oncology Annual Meeting, the most common severe side effects for the group of patients who received Imbruvica included: neutropenia, thrombocytopenia (both decreases in a type of white blood cell) pneumonia, anemia (decrease in red blood cells), rash and diarrhea.
Additionally, the phase 3 SELENE trial comparing Bendeka, Rituxan, R-CHOP (a regimen consisting of cyclophosphamide, doxorubicin, vincristine and prednisone) with placebo and Bendeka, Rituxan, R-CHOP and Imbruvica did not meet its main goal of improved progression-free survival.
Results from the SELENE trial were not yet published or presented at a medical meeting.
“We fully support the FDA accelerated approval pathway, which patients rely on for timely access to promising treatments that may improve or extend their lives. While withdrawing these indications was a difficult decision, we remain confident in the benefit/risk profile of Imbruvica in its approved indications and are committed to its continued development,” said Dr. Craig Tendler, vice president, late development and global medical affairs, Janssen Research & Development, LLC, in a press release.
This decision does not affect any other approved indications for Imbruvica in the United States, according to the press release.
Imbruvica-containing regimens are also used to treat patients with relapsed/refractory mantle cell lymphoma and marginal zone lymphoma — both subtypes of non-Hodgkin lymphoma — as well as chronic lymphocytic leukemia, small lymphocytic leukemia, Waldenström’s macroglobulinemia, and adults and children with previously treated chronic graft-versus host disease.
The drug is a once-daily medication taken orally that blocks the BTK protein, which is a key player in the growth and spread of certain types of cancer cells.
“Imbruvica has transformed how patients with B-cell malignancies are treated and is the most comprehensively studied and prescribed therapy in its class,” Tendler said.
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