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Phase 3 Results for Zydelig® With Bendamustine and Rituximab for Relapsed Chronic Lymphocytic Leukemia (CLL) Presented at American Society of Hematology Annual Meeting
-- Study Shows Statistically Significant Benefit for Zydelig in Progression-Free Survival --

ORLANDO, Fla.--(BUSINESS WIRE)--Dec. 8, 2015-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced 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 percent reduction in the risk of disease progression or death (progression-free survival, PFS) in patients receiving Zydelig plus BR compared to BR alone (hazard ratio (HR) = 0.33; 95 percent CI: 0.24, 0.45; p<0.0001). Additionally, all secondary endpoints, including overall survival (OS), achieved statistical significance in this interim analysis. Detailed results were presented today during the late-breaking abstracts session at the Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida (#LBA-5).

“These new findings add to the role of idelalisib-containing regimens for the treatment of relapsed CLL,” said Andrew D. Zelenetz, MD, PhD, Medical Oncologist and Vice Chair, Medical Informatics, Department of Medicine, Lymphoma Service, Memorial Sloan Kettering Cancer Center. “In this Phase 3 study, adding idelalisib to BR provided not only statistically significant but clinically meaningful improvements in progression-free and overall survival compared to BR, a current standard of care in relapsed/refractory CLL. Further, idelalisib treatment also benefitted patients with genetic factors associated with a poorer prognosis.”

Zydelig is approved in the United States in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. Based on the Study 115 results, Gilead plans to submit supplemental regulatory filings in the U.S. and Europe early next year.

Study 115 enrolled 416 adult patients with previously treated CLL whose disease had progressed less than 36 months following completion of prior therapy, and was not refractory to bendamustine. Eligible patients were randomized (1:1) to receive six cycles of BR over 24 weeks with either Zydelig 150 mg or placebo taken orally twice daily until disease progression or unacceptable toxicity. In November, the trial was unblinded following the recommendation of an independent Data Monitoring Committee.

The primary endpoint was PFS, defined as the time from randomization to definitive disease progression or death, as assessed by an independent review committee. Median PFS for patients receiving Zydelig plus BR was 23.1 months compared to 11.1 months for patients receiving placebo plus BR. Among patients with a 17p deletion or TP53 mutation (Zydelig plus BR: n=69; placebo plus BR: n=68), genetic abnormalities that have been linked to poor prognosis, there was a 50 percent reduction in the risk of disease progression or death (HR=0.50, 95 percent CI: 0.32, 0.77).

The study also found a statistically significant benefit in OS, with a 45 percent reduction in the risk of death among patients receiving Zydelig plus BR compared to those receiving BR alone (HR=0.55; 95 percent CI: 0.36, 0.86; p=0.008). Median OS has not been reached in either arm. The overall response rate (ORR) was 68 percent in the Zydelig arm and 45 percent for the control arm.

Grade ≥3 adverse events for the Zydelig plus BR and placebo plus BR arms, respectively, included neutropenia (60 versus 46 percent), febrile neutropenia (20 versus 6 percent) and diarrhea (7 versus 2 percent). Grade ≥3 elevations in ALT and AST occurred in 21 and 16 percent, respectively, of patients receiving Zydelig plus BR compared to 3 percent and 3 percent in patients receiving BR alone; see below for Important Safety Information, including BOXED WARNING.

Zydelig in combination with bendamustine and rituximab is an investigational regimen and its safety and efficacy have not been established.
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Source: press release, 12/08/15. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...

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Gilead’s Zydelig® Combined with Bendamustine and Rituximab Shows Superior Efficacy to Bendamustine/Rituximab in Phase 3 Study of Patients with Relapsed Chronic Lymphocytic Leukemia
-- Interim Analyses Results from Study 115 to be Presented as a Late-Breaking Abstract at the American Society of Hematology (ASH) Annual Meeting --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 16, 2015-- Following the recommendation by an independent Data Monitoring Committee (DMC), Gilead Sciences, Inc. (NASDAQ:GILD) today announced that its Phase 3 Study 115 evaluating Zydelig® (idelalisib) added to standard therapy in previously-treated chronic lymphocytic leukemia (CLL) patients will be unblinded early. The DMC recommendation is based upon a predefined interim analysis indicating a statistically significant benefit in efficacy for progression-free survival (PFS) and overall survival (OS) in patients receiving Zydelig plus bendamustine and rituximab, compared to those receiving only bendamustine and rituximab. The safety profile of Zydelig was consistent with prior studies. Detailed results from this study will be presented during a late-breaking abstracts session (#LBA-5) at the Annual Meeting of the American Society of Hematology (ASH) in Orlando, Florida taking place December 5-8.

Zydelig is approved in the United States in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities.

“The clinical benefit observed in this Phase 3 study adds to the body of evidence demonstrating the potential of Zydelig-containing treatment regimens for patients with previously treated CLL,” said Norbert W. Bischofberger, PhD, Gilead’s Executive Vice President, Research and Development and Chief Scientific Officer. “We look forward to sharing the detailed scientific data with the hematology community at the upcoming ASH meeting.”

Study 115 is a randomized, double-blind, placebo-controlled, Phase 3 study evaluating the efficacy and safety of Zydelig in combination with bendamustine and rituximab among 416 adult patients with previously treated CLL. Eligible patients were randomized (1:1) to receive six cycles of bendamustine and rituximab over 24 weeks combined with either Zydelig 150 mg or placebo taken orally twice daily continuously until disease progression or unacceptable toxicity. The primary endpoint is PFS.

Additional details contained in the Study 115 abstract are available at https://ash.confex.com/ash/2015/webprogram/start.html. Based on these results, Gilead plans to submit supplemental regulatory filings in the U.S. and Europe early next year.

The use of Zydelig in combination with bendamustine/rituximab is investigational and the safety and efficacy of this combination has not been established.
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Source: press release, 11/16/15. http://investors.gilead.com/phoenix.zhtml?c=69964&p=irol-newsArticle&ID=...

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Norbert W. Bischofberger, PhD, EVP, R&D and CSO, commented on the GS-1101 CLL program. He stated, "In oncology, two phase III clinical trials of GS-1101 for the treatment of chronic lymphocytic leukemia have been initiated. These studies in a placebo-controlled fashion compare GS-1101 added to either Rituximab or to Rituximab with Bendamustine in relapsed refractory CLL patient."
Source: Q2 2012 earnings conference call, 7/26/12.

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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of GS-1101 (CAL-101) in Combination With Bendamustine and Rituximab for Previously Treated Chronic Lymphocytic Leukemia
Estimated Enrollment: 390
Study Start Date: June 2012
Estimated Study Completion Date: December 2017
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Source: clinical trials.gov. http://clinicaltrials.gov/ct2/show/NCT01569295?term=GS-1101&rank=2

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Compound/DeviceSpecialtyIndicationCompound ClassTarget
Zydelig (Idelalisib) (GS-1101) (CAL-101) CLLOncology HematologicChronic lymphocytic leukemia (CLL)PI3K delta inhibitorClass IA phosphoinositide-3 kinases (PI3K)

Mechanism of action: Zydelig (Idelalisib) (GS-1101) (CAL-101) is a small molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA phosphoinositide-3 kinases (PI3K) with potential immunomodulating and antineoplastic activities. PI3K-delta inhibitor CAL-101 inhibits the production of the second messenger phosphatidylinositol-3,4,5-trisphosphate (PIP3), preventing the activation of the PI3K signaling pathway and thus inhibiting tumor cell proliferation, motility, and survival. Unlike other isoforms of PI3K, PI3K-delta is expressed primarily in hematopoietic lineages. The targeted inhibition of PI3K-delta is designed to preserve PI3K signaling in normal, non-neoplastic cells.

Phase of Development: III

Event Type: Data: Phase III trial results

Dates: 2017-07-01 - 2017-12-31

Results: Pending