The Janssen Pharmaceutical Companies of Johnson & Johnson has applied to the European Medicines Agency (EMA) seeking the approval of Imbruvica (ibrutinib) in combination with rituximab as first-line treatment in previously untreated chronic lymphocytic leukaemia (CLL).
Imbruvica is already approved in Europe for chronic lymphocytic leukaemia as a monotherapy or in combination with obinutuzumab in patients who were previously untreated for their condition. The drug is also approved in Europe as a monotherapy or in combination with bendamustine and rituximab (BR) for the treatment of the same disease in adults who had gone through at least one prior therapy.
Janssen is now seeking further expansion of the drug’s label and in this connection has submitted a Type II variation application to the regulator based on the findings of phase 3 E1912 trial.
Imbruvica is a Bruton’s tyrosine kinase (BTK) inhibitor that blocks the BTK protein, whose signalling is required by certain cancer cells to multiply and propagate.
The late-stage trial held in the US assessed 529 patients having previously untreated chronic lymphocytic leukaemia, aged 70 years or younger. The enrolled patients were grouped randomly in a 2:1 ratio to be subjected to ibrutinib plus rituximab or the chemo-immunotherapy FCR.
The primary endpoint of the E1912 trial was progression-free survival (PFS), while overall survival (OS) was one of the secondary endpoints.
The E1912 study showed that ibrutinib plus rituximab delivered superior PFS and OS compared to FCR, a chemotherapy-based standard of care for younger patients having newly diagnosed chronic lymphocytic leukaemia.
Janssen Research & Development clinical development and global medical affairs vice president Craig Tendler said: “The E1912 study demonstrated the important clinical benefit of ibrutinib in combination with rituximab in the frontline setting.
“We remain committed to replacing long-standing use of chemotherapy with ibrutinib-based combination regimens for the treatment of patients with CLL in the frontline setting.”
Apart from chronic lymphocytic leukaemia, the BTK inhibitor is approved in Europe as monotherapy for mantle cell lymphoma and Waldenström’s macroglobulinemia.
Overall, Imbruvica has approval across more than 95 countries for at least one indication. About a year ago, the BTK inhibitor in combination with obinutuzumab was approved in the US as a non-chemotherapy combination regimen for patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma, who are treatment- naïve.