Days after gaining approval for 3 indications in the US, idelalisib (Zydelig) has earned a positive opinion from the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP).
The CHMP is recommending the PI3K delta inhibitor for the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).
If approved, the drug would be used as monotherapy for adults with FL that is refractory to 2 prior lines of treatment.
Idelalisib would also be used in combination with rituximab for adults with CLL who have received at least 1 prior therapy or as first-line treatment in CLL patients who have 17p deletion or TP53 mutation and cannot receive chemo-immunotherapy.
The CHMP’s recommendation for idelalisib (150 mg film-coated tablets) will be reviewed by the European Commission, which has the authority to approve medicines for use in the 28 countries of the European Union.
The CHMP’s positive opinion of idelalisib is based on data from 2 clinical trials—Study 116 and Study 101-09.
Study 116: Idelalisib in CLL
This phase 3 trial was stopped early because idelalisib had a significant impact on progression-free survival.
The study included 220 CLL patients who could not receive chemotherapy. Half were randomized to receive idelalisib plus rituximab, and the other half were randomized to rituximab plus placebo.
Patients in the idelalisib arm had a much higher overall response rate than patients in the placebo arm—81% and 13%, respectively (P<0.001). But all responses were partial.
At 24 weeks, the rate of progression-free survival was 93% in the idelalisib arm and 46% in the placebo arm (P<0.001). The median progression-free survival was 5.5 months in the placebo arm and not reached in the idelalisib arm (P<0.001).
At 12 months, the overall survival rate was 92% in the idelalisib arm and 80% in the placebo arm (P=0.02).
Most adverse events, in either treatment arm, were grade 2 or lower. The most common events in the idelalisib arm were pyrexia, fatigue, nausea, chills, and diarrhea. In the placebo arm, the most common events were infusion-related reactions, fatigue, cough, nausea, and dyspnea.
There were more serious adverse events in the idelalisib arm than in the placebo arm—40% and 35%, respectively. The most frequent serious events were pneumonia, pyrexia, and febrile neutropenia (in both treatment arms).
Study 101-09: Idelalisib in FL
In this phase 2 trial, idelalisib was given as a single agent to patients with indolent non-Hodgkin lymphoma who were refractory to rituximab and chemotherapy containing an alkylating agent.
In the 72 patients with FL, the overall response rate was 54%, and the complete response rate was 8%. The median duration of response was not reached (range, 0-14.8 months).
Improvements in patient survival or disease-related symptoms have not been established.
The most common grade 3 or higher adverse events were neutropenia (27%), elevations in aminotransferase levels (13%), diarrhea (13%), and pneumonia (7%).
About idelalisib
Idelalisib is an oral inhibitor of PI3K delta, a protein that plays a role in the activation, proliferation, and viability of B cells. PI3K delta signaling is active in many B-cell leukemias and lymphomas, and, by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.
Idelalisib is being developed by Gilead Sciences. On July 23, the drug received US Food and Drug Administration approval for use in combination with rituximab to treat patients with relapsed CLL who cannot receive rituximab alone. The agency also granted idelalisib accelerated approval to treat patients with relapsed FL or small lymphocytic lymphoma who have received at least 2 prior systemic therapies.
