Imbruvica strengthens its case against blood cancers

Longer-term follow-up data on Imbruvica (ibrutimib) has shown its continued effectiveness against chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL), according to findings presented by Janssen at the American Society of Haematology (ASH) meeting this week.

Imbruvica is a first-in-class, once-daily, oral Bruton’s tyrosine kinase (BTK) inhibitor that promises blockbuster status. Peak sales of between $4-6.5 billion are predicted, if it can add further indications.

The first set of data detailed a 16-month follow-up study on the phase III RESONATE trial, which showed the drug significantly improved progression-free survival (PFS) and overall survival (OS) versus ofatumumab in patients with relapsed or refractory (RR) chronic lymphocytic leukaemia (CLL) regardless of baseline cytogenetics, or number of prior therapies.

At 12 months, 84 per cent of the Imbruvica patients continued progression-free, compared to 19 per cent in patients randomised to receive ofatumumab. The OS for patients on Imbruvica was significantly longer than for patients in the ofatumumab arm, with 18-month survival rates of 85 per cent versus 78 per cent, despite 62 per cent of ofatumumab patients crossing over to receive Imbruvica.

Study presenter, Dr Jennifer Brown, director of the Chronic Lymphocytic Leukemia Center, Dana-Farber Cancer Institute and associate professor of medicine, Harvard Medical School, said, “What was compelling about this study was Imbruvica improved progression-free survival, versus ofatumumab, regardless of baseline cytogenetics or number of prior therapies.”

The second longer-term follow-up presentation reported two-year data from the phase II PCYC-1104 study in patients with RR mantle cell lymphoma (MCL). In this, Imbruvica was associated with a median PFS of 13 months and median OS of 22.5 months. Almost one-third of RR MCL patients (31 per cent) remained progression-free at two years and almost half (47 per cent) of them are still alive.

Imbruvica works by forming a strong covalent bond with BTK to block the transmission of cell survival signals within the malignant B cells. By blocking this BTK protein, it helps kill and reduce the number of cancer cells and slows down the worsening of the cancer.

Investigational uses for ibrutinib, alone and in combination with other treatments, are underway in several blood cancers including CLL, MCL, Waldenström’s macroglobulinemia (WM), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and multiple myeloma (MM). One notable deal was made in November with AstraZeneca (AZ), to investigate a combination of AZ’s MEDI4736 immunotherapy candidate with Imbruvica in haematological cancers including DLBCL and FL.

Imbruvica received European Commission approval in October for the treatment of adult patients with RR MCL, and adult patients with CLL who have received at least one prior therapy, or in first line in the presence of 17p deletion (del17p CLL) or TP53 mutation in patients with CLL who are unsuitable for chemo-immunotherapy.

A Type II variation application was also submitted to the European Medicines Agency (EMA) in November to expand the marketing authorisation to include a new therapeutic indication for the treatment of adult patients with (WM).

Imbruvica is co-developed by Janssen’s Cilag GmbH International and Pharmacyclics.


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