Gilead’s Zydelig® Combined with Bendamustine & Rituximab Shows Superior Efficacy to Bendamustine/Rituximab in Phase 3 Stud...
November 16 2015 - 09:00AM
Business Wire
-- Interim Analyses Results from Study 115
to be Presented as a Late-Breaking Abstract at the American Society
of Hematology (ASH) Annual Meeting --
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.
About Zydelig
(idelalisib)
Zydelig is an oral inhibitor of phosphoinositide 3-kinase (PI3K)
delta, a protein that plays a role in the activation, proliferation
and viability of B cells, a critical component of the immune
system. PI3K delta signaling is active in many B-cell leukemias and
lymphomas, and by inhibiting the protein, Zydelig blocks several
cellular signaling pathways that drive B-cell viability.
Important U.S. Safety
Information
BOXED WARNING: FATAL AND
SERIOUS TOXICITIES: HEPATIC, SEVERE
DIARRHEA, COLITIS, PNEUMONITIS AND
INTESTINAL PERFORATION
- Fatal and/or serious hepatotoxicity
occurred in 14 percent of Zydelig-treated patients. Monitor hepatic
function prior to and during treatment. Interrupt and then reduce
or discontinue Zydelig as recommended.
- Fatal and/or serious and severe
diarrhea or colitis occurred in 14 percent of Zydelig-treated
patients. Monitor for the development of severe diarrhea or
colitis. Interrupt and then reduce or discontinue Zydelig as
recommended.
- Fatal and serious pneumonitis can
occur. Monitor for pulmonary symptoms and bilateral interstitial
infiltrates. Interrupt or discontinue Zydelig as
recommended.
- Fatal and serious intestinal
perforation can occur in Zydelig-treated patients. Discontinue
Zydelig for intestinal perforation.
Contraindications
- History of serious allergic
reactions, including anaphylaxis and toxic epidermal necrolysis
(TEN).
Warnings and Precautions
- Hepatotoxicity: Findings were
generally observed within the first 12 weeks of treatment and
reversed with dose interruption. Upon rechallenge at a lower dose,
ALT/AST elevations recurred in 26% of patients. In all patients,
monitor ALT/AST every 2 weeks for the first 3 months, every 4 weeks
for the next 3 months, and every 1 to 3 months thereafter. If
ALT/AST is >3x upper limit of normal (ULN), monitor for liver
toxicity weekly. If ALT/AST is >5x ULN, withhold Zydelig and
monitor ALT/AST and total bilirubin weekly until resolved.
Discontinue Zydelig for recurrent hepatotoxicity. Avoid concurrent
use with other hepatotoxic drugs.
- Severe diarrhea or colitis:
Grade 3+ diarrhea can occur at any time and responds poorly to
antimotility agents. Avoid concurrent use with other drugs that
cause diarrhea.
- Pneumonitis: Evaluate for
pneumonitis in patients presenting with pulmonary symptoms such as
cough, dyspnea, hypoxia, interstitial infiltrates on radiologic
exam, or oxygen saturation decline by ≥5 percent.
- Intestinal perforation: Advise
patients to promptly report any new or worsening abdominal pain,
chills, fever, nausea, or vomiting.
- Severe cutaneous reactions: One
case of TEN occurred in a study of Zydelig in combination with
rituximab and bendamustine. Other severe or life-threatening (grade
≥3) cutaneous reactions have been reported. Monitor patients for
the development of severe cutaneous reactions and discontinue
Zydelig if a reaction occurs.
- Anaphylaxis: Serious allergic
reactions including anaphylaxis have been reported. Discontinue
Zydelig permanently and institute appropriate supportive measures
if a reaction occurs.
- Neutropenia: Treatment-emergent
grade 3-4 neutropenia occurred in 31 percent of Zydelig-treated
patients in clinical trials. In all patients, monitor blood counts
≥every 2 weeks for the first 3 months. In patients with neutrophil
counts <1.0 Gi/L, monitor weekly.
- Embryo-fetal toxicity: Zydelig
may cause fetal harm. Women who are or become pregnant while taking
Zydelig should be apprised of the potential hazard to the fetus.
Advise women to avoid pregnancy while taking Zydelig and to use
effective contraception during and at least 1 month after treatment
with Zydelig.
Adverse Reactions
- Most common adverse reactions
(incidence ≥10 percent and ≥2 percent than rituximab alone, all
grades) were pyrexia, nausea, pneumonia, diarrhea, chills, rash,
vomiting and headache.
- Most frequent serious adverse
reactions (SAR) were pneumonia (17 percent), pyrexia (9
percent), sepsis (8 percent), febrile neutropenia (5 percent) and
diarrhea (5 percent); SAR were reported in 49 percent of patients
and 10 percent of patients discontinued due to adverse
reactions.
- Most common lab abnormalities
(incidence ≥30 percent and ≥5 percent than rituximab alone; all
grades) were neutrophils decreased, hypertriglyceridemia,
hyperglycemia and ALT elevation.
Drug Interactions
- CYP3A inducers: Avoid
coadministration with strong CYP3A inducers.
- CYP3A inhibitors: When
coadministered with strong CYP3A inhibitors, monitor closely for
Zydelig toxicity.
- CYP3A substrates: Avoid
coadministration with CYP3A substrates.
Dosage and Administration
- Adult starting dose: One 150 mg
tablet twice daily, swallowed whole with or without food. Continue
treatment until disease progression or unacceptable toxicity. The
safe dosing regimen for patients who require treatment longer than
several months is unknown.
- Dose modification: Consult the
Zydelig full Prescribing Information for dose modification and
monitoring recommendations for the following specific toxicities:
pneumonitis, ALT/AST elevations, bilirubin elevations, diarrhea,
neutropenia, and thrombocytopenia. For other severe or
life-threatening toxicities, withhold Zydelig until toxicity is
resolved and reduce the dose to 100 mg, twice daily, upon resuming
treatment. If severe or life-threatening toxicities recur upon
rechallenge, Zydelig should be permanently discontinued.
About Gilead
Sciences
Gilead Sciences is a biopharmaceutical company that discovers,
develops and commercializes innovative therapeutics in areas of
unmet medical need. The company’s mission is to advance the care of
patients suffering from life-threatening diseases worldwide. Gilead
has operations in more than 30 countries worldwide, with
headquarters in Foster City, California.
Forward-Looking
Statement
This press release includes forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including the risk that Gilead may be unable to submit supplemental
filings for the use of Zydelig in combination with bendamustine and
rituximab in the U.S. and Europe in the currently anticipated
timelines. In addition, the regulatory filings may not be approved
by regulatory agencies and marketing approvals, if granted, may
have significant limitations on their use. As a result, Zydelig in
combination with bendamustine and rituximab may never be
successfully commercialized. Further, there is the possibility of
unfavorable results from other clinical trials involving Zydelig.
These risks, uncertainties and other factors could cause actual
results to differ materially from those referred to in the
forward-looking statements. The reader is cautioned not to rely on
these forward-looking statements. These and other risks are
described in detail in Gilead’s Quarterly Report on Form 10-Q for
the quarter ended September 30, 2015, as filed with
the U.S. Securities and Exchange Commission. All
forward-looking statements are based on information currently
available to Gilead, and Gilead assumes no obligation to update any
such forward-looking statements.
U.S. full prescribing information, including
BOXED WARNING for Zydelig is available
at www.gilead.com.
Zydelig is a registered trademark of Gilead
Sciences, Inc.
For more information on Gilead Sciences,
please visit the company’s website at www.gilead.com, follow
Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs
at 1-800-GILEAD-5 or 1-650-574-3000.
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version on businesswire.com: http://www.businesswire.com/news/home/20151116005455/en/
Gilead Sciences, Inc.Patrick O’Brien, 650-522-1936
(Investors)Nathan Kaiser, 650-522-1853 (Media)
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