Zydelig (idelalisib; Gilead) is an oral, highly selective inhibitor of the phosphoinositide 3-kinase (PI3K) isoform p110-delta. In vitro studies have demonstrated that Zydelig results in decreased phosphorylation Akt and other downstream effectors, an increase in poly (ADP-ribose) polymerase and caspase cleavage, and an induction of apoptosis. Further studies have shown that Zydelig not only causes cell death, but also reduces the interactions that retain chronic lymphocytic leukemia (CLL) cells in protective microenvironments.
Zydelig (idelalisib; Gilead) is the first selective inhibitor of phosphoinositide 3-kinase delta (PI3K-
delta) approved for the follicular lymphoma (FL) market. Demonstrating efficacy in previously treated FL patients who are refractory to both Rituxan (rituximab; Roche/Biogen/Chugai/Zenyaku Kogyo) and alkylating agents, Zydelig gained approval in the US and EU as a single agent for relapsed FL patients who have received at least two prior therapies (Zydelig prescribing information, 2014). Although this satisfied a significant unmet need within the FL market, larger commercial success of Zydelig depended on future potential label expansions to earlier lines of treatment as a combination therapy. However, the two ongoing Phase III trials of Zydelig in the second-line treatment setting, in combination with Rituxanin and Rituxan plus Treanda (bendamustine; Teva) (ClinicalTrials.gov identifiers: NCT01732913 and NCT01732926, respectively) were put on hold. Gilead suspended the trials after the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) initiated reviews of Zydelig in March 2016 following an observed increased rate of serious adverse advents in clinical trials of the drug in combination with other cancer medicines (EMA press release, 2016; FDA Drug Safety Announcement, 2016). This hold on combination trials of Zydelig potentially limits its growth opportunities in the FL market.
LIST OF FIGURES
12 Figure 1: Datamonitor Healthcare’s drug assessment summary of Zydelig for CLL
13 Figure 2: Datamonitor Healthcare’s drug assessment summary of Zydelig for CLL
15 Figure 3: Zydelig sales for CLL across the US and five major EU markets, by country, 2017–26
21 Figure 4: Zydelig for follicular lymphoma – SWOT analysis
22 Figure 5: Datamonitor Healthcare’s drug assessment summary of Zydelig for follicular lymphoma
23 Figure 6: Datamonitor Healthcare’s drug assessment summary of Zydelig for follicular lymphoma
25 Figure 7: Zydelig sales for follicular lymphoma across the US and five major EU markets, by country, 2017–26
LIST OF TABLES 5 Table 1: Zydelig drug profile
6 Table 2: Approval history of Zydelig for CLL in the US, Japan, and five major EU markets
8 Table 3: Trials of Zydelig for CLL
11 Table 4: Zydelig for CLL – SWOT analysis
18 Table 5: Zydelig drug profile
20 Table 6: Zydelig pivotal trial data in follicular lymphoma
26 Table 7: Zydelig sales for follicular lymphoma across the US and five major EU markets, by country ($m), 2017–26
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