ZydeligChronic lymphocytic leukaemia (CLL), relapsed - in combination with bendamustine and rituximab
Development and Regulatory status
Dec 18: EU development discontinued .
Feb 18: EU filing withdrawn after the CHMP had evaluated the documentation provided by the company and formulated lists of questions. Gilead stated that the withdrawal is based on CHMP opinion that the data supplied did not provide sufficient evidence to conclude that the benefits outweigh the risks .
Oct 17: Will be filed via the centralised procedure in the EU .
Dec 16: Still listed in Gilead pipeline .
Trial or other data
Jan 17: Interim results of PIII study (NCT01569295) published in The Lancet. RCT (n=416) found a PFS of 20.8 months with idelalisib vs 11.1 months with placebo (HR 0.33, 95% CI 0.25-0.44). Serious AEs were more common with idelalisib (68% vs 44%) as were treatment emergent SEs leading to death (11% vs 7%) .
May 16: PIII (NCT01569295) study has completed recruitment and primary outcome data collection should be complete .
May 16: MHRA issues new interim treatment recommendations (with respect to risk of infection) for idelalisib in light of new findings from clinical trials .
Mar 16: PRAC recommends that all patients treated with Zydelig should receive antibiotics to prevent Pneumocystisjirovecii pneumonia (PCP). Patients should also be monitored for infection and have regular blood tests for white cell counts. Zydelig should not be started in patients with a generalised infection. It should also not be started in previously untreated patients with CLL whose cancer cells have certain genetic mutations (17p deletion or TP53 mutation) .
Mar 16: The FDA have also issued an alert regarding reports of an increased rate of adverse events, including deaths, in clinical trials with idelalisib in combination with other cancer medicines. Gilead has confirmed that they are stopping six clinical trials in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma and indolent non-Hodgkin lymphomas .
Mar 16: The EMA, at the request of the European Commission, is reviewing idelalisib following concerns over serious adverse events in ongoing trials. An increased rate of serious adverse events including deaths, mostly due to infections, was seen in three clinical trials1 investigating the medicine in combination with other cancer medicines .
Dec 15: Gilead announce results from a prespecified interim analysis of a Phase 3 study (Study 115) evaluating Zydelig® (idelalisib) in combination with bendamustine and rituximab (BR) for patients with previously treated CLL. The analysis found a 67% reduction in risk of disease progression or death (progression-free survival, PFS) in patients receiving Zydelig plus BR compared to BR alone (HR 0.33; 95% CI: 0.24, 0.45; p<0.0001). All secondary endpoints, including overall survival (OS), achieved statistical significance in this interim analysis .
Mar 15: NCT01569295 ongoing; primary completion date Dec 2016 .
Nov 14: PIII (NCT01569295) is recruiting 390 pts in the EU (incl UK), USA, Canada and other countries with previously treated recurrent CLL. they will be randomised to idelalisib 150mg oral twice daily in combination with rituximab 375mg/m2 IV on day 1, then 500mg/m2 every 28 days (for a maximum of 6 infusions), and bendamustine 70mg/m2 IV on 2 consecutive days every 28 days (for a maximum of 12 infusions); or placebo in combination with rituximab 375mg/m2 IV on day 1, then 500mg/m2 every 28 days (for a maximum of 6 infusions), and bendamustine 70mg/m2 IV on 2 consecutive days every 28 days (for a maximum of 12 infusions). The primary outcome is progression-free survival up to 30 months. Study completion is expected Dec 17 .