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Idelalisib Use Expands With New CLL Indication Pending

Silas Inman @silasinman
Published: Thursday, Jul 30, 2015

Dr. Jeffrey A. Jones from Ohio State University

Jeffrey A. Jones, MD, MPH

The utilization of idelalisib (Zydelig) increased substantially between the first and second quarters of 2015, representing promising growth in a highly competitive setting, according to Gilead Sciences, the developer of the drug.

Sales for the PI3K delta inhibitor rose from $26 million in the first quarter of 2015 to $30 million in the second, representing an 15% increase. At the time of the second quarter analysis, idelalisib had been on the market for nearly one year, having gained approval chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma in July 2014. Sales immediately following the approval totaled $6 million and $17 million, in the third and fourth quarters of 2014, respectively.

Building on this success, Gilead has filed an application with the FDA to expand the indication of idelalisib to include use in combination with ofatumumab for patients with relapsed CLL. This new application is based on findings from a phase III trial known as Study 119, which showed an improvement in objective response rates (ORR), progression-free survival (PFS), and lymph node response (LNR) with the combination of idelalisib and ofatumumab compared with the CD20 inhibitor alone in patients with previously treated CLL.1

"It has been fascinating the rate of innovation we have seen in the blood cancer space, and it has gotten extremely crowded, leaving fewer opportunities for new products," John F. Milligan, PhD, president and chief operating officer of Gilead, said during a webcast. "It's clear that we're going to be active, and we're open to opportunities that can better our portfolio."

Study 119 randomized 261 patients with CLL who progressed within 24 months from their last therapy to idelalisib plus ofatumumab (n = 174) or single-agent ofatumumab (n = 87). Patients were stratified based on relapsed versus refractory status, 17p deletion (del17p) and/or TP53 mutation status, and whether they harbored an IGHV mutation.

The combination reduced the risk of disease progression by 73% versus single-agent ofatumumab, with a medium PFS of 16.3 versus 8.0 months, respectively (HR = 0.27; P <.0001). In patients with del17p or TP53 mutations, the median PFS was 13.7 versus 5.8 months, respectively (HR = 0.33; P <.0001).

The overall response rate was 75.3% in the combination arm versus 18.4% in the ofatumumab alone arm (odds ratio [OR] = 15.9; P <.0001). In the ofatumumab arm, the LNR rate was 93.3% versus 4.9% in the ofatumumab arm (OR = 487; P <.0001).

However, at the time of the analysis, improvements in ORR, PFS, and LNR had not yet translated into extensions in overall survival (OS), with data still maturing. Medium OS was 20.9 months in the idelalisib/ofatumumab arm compared with 19.4 months in the ofatumumab arm (HR = 0.74; P = .27).

“The data reported reinforce prior results showing that idelalisib, here in combination with the anti-CD20 monoclonal antibody ofatumumab, not only significantly improved overall and lymph node response rates, but more importantly progression-free survival in patients with previously treated CLL,” lead investigator Jeffrey A. Jones, MD, MPH, Associate Professor of Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, said in a statement. “Importantly, these improvements were also observed in patients with genetic features typically associated with poor prognosis.”

The initial CLL approval for idelalisib was based on early data from the phase III Study 116 trial that randomized 220 patients in a 1:1 ratio to receive oral idelalisib plus rituximab (n = 110) or rituximab and placebo (n = 110). Patients had received a median of 3 prior therapies, 44% had del17p or TP53 mutations, and 84% were IGHV-unmutated.

In data from a second interim analysis presented at the 2014 ASH Annual Meeting,2 the ORR with idelalisib plus rituximab was 77% versus 15% with rituximab and placebo (Odds ratio = 19.6; 95% CI, 9.6-39.9). The median OS was not reached in either arm, with an early 72% increase seen with idelalisib (HR = 0.28; 95% CI, 0.11-0.69).

Median PFS was 5.5 months with placebo and rituximab and was not yet reached with idelalisib, representing a 82% improvement (HR = 0.18; 95% CI, 0.10-0.32). This benefit was consistent across subgroups. The 12-month PFS rates were 66% versus 13% for idelalisib and placebo, respectively.

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