Johnson & Johnson (J&J) and Pharmacyclics are on course to file ibrutinib in the treatment of B cell malignancies by early 2014 after positive phase II data.
The data show that ibrutinib achieved an overall response rate (ORR) of 68 per cent when used as a monotherapy in relapsed/refractory mantle cell lymphoma and 41 per cent in a subgroup of diffuse large B-cell lymphoma patients.
In mantle cell lymphoma patients the drug achieved progression-free survival of nearly 14 months, with around 58 per cent of patients still alive after 18 months. The mantle cell lymphoma study had no comparator arm but the results are “exciting”, according to lead investigator Prof Simon Rule of Derriford Hospital in the UK, “particularly as the responses appear to last”.
The diffuse large B-cell lymphoma study showed that ibrutinib was more effective in patients with a particular disease subtype (Activated B-cell-like; ABC) that is known to be dependent on B cell pathways. Treatment of patients with the ABC subtype achieved an ORR of 41 per cent while the rate for those with another subtype (Germinal Center B-cell-like; GCB) was just 5 per cent.
Median overall survival was 9.76 months for the ABC group, compared to 3.35 months for the GCB subtype, said lead investigator Sven de Vos of UCLA Medical Centre in Los Angeles. Both studies were presented at the European Hematology Association annual meeting in Stockholm.
Analysts have suggested that ibrutinib could make annual sales of around $500m at peak across all its indications, with the largest proportion likely to come from its use in chronic lymphocytic leukaemia for which it is currently in three phase III trials.
The drug has already garnered no less than three ‘breakthrough’ designations from the US FDA – for MCL, Waldenstrom’s macroglobulinemia, and CLL or small lymphocytic leukaemia (SLL) patients who express the 17p deletion genetic mutation.
It looks likely to be the first drug in the new breakthrough category to be reviewed by the FDA, with some commentators suggesting it could enjoy a very fast review and garner sales of $200m-plus in 2014 if it gets a green light early enough in the year.