Imbruvica gets positive EMA Committee opinion for untreated mantle cell lymphoma eligible for Stem Cell Transplant: Janssen-Cilag International
Beerse: Janssen-Cilag International NV, a Johnson & Johnson company, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval for an indication extension of IMBRUVICA (ibrutinib) in frontline mantle cell lymphoma (MCL).
Ibrutinib is a once-daily oral medication that is jointly developed and commercialised by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company. Ibrutinib blocks the BTK protein, which is needed by normal and abnormal B-cells, including specific cancer cells, to multiply and spread. By blocking BTK, ibrutinib may help move abnormal B-cells out of their nourishing environments and inhibits their proliferation.
The recommendation is for ibrutinib in combination with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (ibrutinib + R-CHOP) alternating with R-DHAP (or R-DHAOx)* without ibrutinib, followed by ibrutinib monotherapy, for the treatment of adult patients with previously untreated MCL who would be eligible for autologous stem cell transplant (ASCT). The extended indication is based on data from the pivotal Phase 3 TRIANGLE study.
“The CHMP recommendation is an important milestone for patients with previously untreated MCL, an aggressive disease which requires complex and challenging treatment,” said Ester in’t Groen, EMEA Therapeutic Area Head Haematology, Johnson & Johnson Innovative Medicine. “We are excited by the innovation that ibrutinib continues to bring and hope to soon offer patients this frontline option that has demonstrated improved overall survival without the burden, toxicity and time in hospital associated to an ASCT-based treatment regimen.”
The CHMP recommendation for ibrutinib is supported by data from the randomised Phase 3 TRIANGLE study, conducted by the European MCL Network ( NCT02858258 ), which evaluated 870 patients across three treatment arms to assess whether the addition of ibrutinib to chemotherapy with or without ASCT could improve outcomes and potentially remove the need for transplant in patients with previously untreated MCL who were suitable for high-dose treatment. The study demonstrated that adding ibrutinib to chemotherapy followed by a 2-year fixed-duration maintenance period instead of ASCT provides significantly longer overall survival and superior failure-free survival compared to the chemotherapy regimen including ASCT.
“At Johnson & Johnson, we are committed to improving outcomes for patients facing complex blood cancers,” said Jessica Vermeulen, Vice President, Lymphoma & Leukemia Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “The TRIANGLE study, conducted by the European MCL Network, affirms the potential emergence of a new standard of care for transplant eligible patients diagnosed with MCL and represents the first major step forward for these patients in many years. We look forward to working together to bring this transplant-free therapeutic option to the MCL community.”
MCL is a rare, aggressive form of non-Hodgkin lymphoma. The current standard of care in the frontline setting for young and fit patients is a chemotherapy regimen including ASCT, which can be associated with severe toxicities, lengthy hospital stays and high health resource utilisation. The addition of fixed-duration ibrutinib to chemotherapy offers the potential for long treatment-free remissions while avoiding the burden of stem cell transplant. If approved, ibrutinib would become the first Bruton’s Tyrosine Kinase inhibitor (BKTi) for frontline treatment of transplant eligible MCL patients.
Ibrutinib is approved in more than 100 countries and has been used to treat more than 325,000 patients worldwide. There are more than 50 company-sponsored clinical trials, including 18 Phase 3 studies, over 11 years evaluating the efficacy and safety of ibrutinib. In October 2021, ibrutinib was added to the World Health Organization’s Model Lists of Essential Medicines (EML), which refers to medicines that address global health priorities and which should be available and affordable for all.
Ibrutinib was first approved by the European Commission (EC) in 2014, and approved indications to date include:
- As a single agent or in combination with rituximab or obinutuzumab or venetoclax for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL)
- As a single agent or in combination with bendamustine and rituximab (BR) for the treatment of adult patients with CLL who have received at least one prior therapy
- As a single agent for the treatment of adult patients with relapsed or refractory MCL
- As a single agent for the treatment of adult patients with Waldenström’s macroglobulinaemia (WM) who have received at least one prior therapy, or in first line treatment for patients unsuitable for chemo-immunotherapy. In combination with rituximab for the treatment of adult patients with WM
