The Committee for Medicinal Products for Human Use (CHMP), an arm of the European Medicines Agency, has recommended the expansion of the current marketing authorization for Imbruvica (ibrutinib) to include two new indications in the European Union.
The first indication is to be used in combination with Gazyva (obinutuzumab) for the treatment of adult patients with untreated chronic lymphocytic leukemia (CLL). The second indication is to be used together with Rituxan (rituximab) in adult patients with Waldenström’s macroglobulinemia (WM), a rare type of non-Hodgkin’s lymphoma.
“We are incredibly encouraged by these CHMP recommendations, which represent our continued commitment to develop chemotherapy-free combinations for those living with CLL and WM,” Dr. Patrick Laroche, of Janssen-Cilag France, said in a press release. “Ibrutinib has been used to treat more than 140,000 patients worldwide and we are continuing to deliver on our ambition to optimise outcomes for patients with complex B-cell malignancies, that have in the past been very difficult to treat.”
Imbruvica — jointly developed and commercialized by Janssen and Pharmacyclics, an AbbVie company — is a first-in-class inhibitor of Bruton’s tyrosine kinase (BTK). BTK is an enzyme that plays an important role in the development and survival of immune B-cells and is currently being explored as a therapeutic target to treat different types of B-cell cancers.
CHMP’s recommendation for the use of Imbruvica in combination with Gazyva for the treatment of CLL was based on findings from the multicenter, randomized, open-label iLLUMINATE Phase 3 trial (NCT02264574).
In the study, 229 patients newly diagnosed with CLL or small lymphocytic lymphoma (SLL) were randomly assigned to be treated with Imbruvica in combination with Gazyva, or with Leukeran (chlorambucil) in combination with Gazyva. The study’s primary endpoint was to assess patients’ progression-free survival (PFS or the time patients lived without their disease worsening).
The findings, recently published in The Lancet Oncology, showed that:
- At month 30, 79% of the patients treated with Imbruvica and Gazyva were alive and progression-free, while 31% of those treated with Leukeran and Gazyva achieved the same outcome.
- Serious adverse events were more common among patients treated Imbruvica (58%) than among those treated with Leukeran (35%).
- Serious or life-threatening adverse events occurred in both groups and included neutropenia (low white-blood cell count) and thrombocytopenia (low platelet count).
CHMP’s recommendation for the use of Imbruvica in combination with Rituxan for the treatment of WM was based on findings from the multicenter, randomized, double-blind, placebo-controlled iNNOVATE Phase 3 trial (NCT02165397).
In the study, 150 patients with untreated and relapsed or refractory WM were randomly assigned to be treated with Imbruvica in combination with Rituxan, or with a placebo in combination with Rituxan. The study’s primary endpoint was to assess patients’ PFS.
The findings, presented at the 60th Annual Meeting of the American Society of Hematology in San Diego, showed that:
- At month 30, 79% of the patients treated with Imbruvica were alive and progression-free, compared to 41% of those treated with a placebo.
- Serious adverse events were more common among patients treated Imbruvica (43%) than among those treated with a placebo (33%).
- Serious or life-threatening adverse events occurred in 61% of patients from both groups.
“This is an important step forward in further enhancing our ability as hematologists to meet the treatment needs of more patients with these complex blood cancers,” said Alessandra Tedeschi, medical director of the department of hematology, Niguarda Hospital, Milan, Italy, and investigator in both trials.
“Ibrutinib has already offered important progress in both CLL and WM in the indications for which it is currently approved, and these new combination regimens show the potential to further extend the remission period for patients versus standard of care,” he added.
Imbruvica has been approved in the U.S. for both indications. In Europe, CHMP’s recommendations will soon be reviewed by the European Commission, which will make the final decision about the approval of Imbruvica for both indications.