The European Commission has granted marketing authorization for Zydelig ( Idelalisib ), 150 mg tablets, a first-in-class oral treatment for two incurable blood cancers: chronic lymphocytic leukemia ( CLL ) and follicular lymphoma ( FL ).
For the treatment of chronic lymphocytic leukemia, Zydelig has been approved for use in combination with Rituximab ( MabThera ) for patients who have received at least one prior therapy; or as first-line treatment in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.
For the treatment of follicular lymphoma, Zydelig has been approved as a monotherapy in patients who are refractory to two prior lines of treatment. Zydelig inhibits PI3K delta, a protein that is overexpressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells.

The approval of Zydelig in chronic lymphocytic leukemia is supported primarily by data from a randomized, placebo-controlled phase 3 trial ( Study 116 ) of Zydelig plus Rituximab in 220 patients with relapsed chronic lymphocytic leukemia who were not able to tolerate standard chemotherapy.
Study 116 was stopped early in October 2013 by an independent Data Monitoring Committee due to a highly statistically significant benefit in progression-free survival in the Zydelig plus Rituximab arm compared with the Rituximab only treatment arm ( hazard ratio, HR=0.18 ( 95% CI: 0.10, 0.32 ), p less than 0.0001 ). Median progression-free survival was not reached in the Zydelig plus Rituximab arm ( 95% CI: 10.7 months, NR ) and was 5.5 months in the placebo plus Rituximab arm ( 95% CI: 3.8, 7.1 ).

The approval in follicular lymphoma, the most common type of indolent non-Hodgkin lymphoma ( iNHL ), is supported by data from a single-arm phase 2 study ( Study 101-09 ) of Zydelig monotherapy in 125 iNHL patients refractory to Rituximab and alkylating-agent-containing chemotherapy.
In the 72 patients with follicular lymphoma, in this study, Zydelig achieved an overall response rate of 54% and the median duration of response was not reached ( range: 0.0, 14.8+ months ).

Adverse drug reactions ( including Grade greater than or equal to 3 ) reported in clinical studies in patients with hematological malignancies receiving Zydelig included infections, neutropenia, pneumonitis, diarrhea/colitis, increased transaminase, rash and pyrexia.

Zydelig is an oral inhibitor of phosphoinositide 3-kinase ( PI3K ) delta, a protein that plays a role in the activation, proliferation and viability of B cells, a critical component of the immune system. PI3K delta signalling is active in many B-cell leukemias and lymphomas, and by inhibiting the protein, Zydelig blocks several cellular signalling pathways that drive B-cell viability. ( Xagena )

Source: Gilead, 2014

XagenaMedicine2014