December 08, 2014
Gilead Presents Follow-up Data from Zydelig Registrational Studies in Patients with Chronic Lymphocytic Leukemia, Follicular Lymphoma and Small Lymphocytic Lymphoma
-- Results Describing Long-Term Safety and Disease Control Presented at the 56th American Society of Hematology Annual Meeting --
Zydelig is indicated in
“The results presented this week demonstrate the long-term benefit of
Zydelig in patient populations that often have limited or no treatment
options due to age or lack of response to existing therapies,” said
Study 101-09 in iNHL
Study 101-09 (Abstract #1708) is a single-arm Phase 2 study evaluating
idelalisib monotherapy in 125 patients with previously treated iNHL that
is refractory both to rituximab and to alkylating-agent-containing
chemotherapy, a patient population that has few if any treatment
options. At the most recent data analysis cutoff (
The most common Grade ≥3 adverse events among all patients were diarrhea/colitis (19 percent) and pneumonia (12 percent). Grade ≥3 transaminase elevations occurred in 14 percent of patients.
Long-Term Data in CLL
Additional long-term data are being presented from Study 116 of idelalisib in previously treated CLL patients.
Study 116 (Abstract #330) was a randomized, placebo-controlled study evaluating idelalisib plus rituximab versus rituximab alone in 220 patients with relapsed CLL who were not able to tolerate standard chemotherapy. Patients in this study were eligible to continue receiving idelalisib therapy in an open-label extension study (Study 117). Results from the primary and the extension study show that among the 110 patients randomized to receive idelalisib plus rituximab, the median PFS has now been reached, and is 19.4 months.
In Study 116/117 the most common Grade ≥3 adverse events in patients receiving idelalisib plus rituximab were diarrhea/colitis (16 percent) and pneumonia (13 percent). Grade ≥3 transaminase elevations occurred in 6 percent of patients.
The Zydelig U.S. Prescribing Information includes a BOXED WARNING regarding fatal and serious toxicities of hepatotoxicity, severe diarrhea/colitis, pneumonia, and intestinal perforation; see below for Important Safety Information.
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.
The clinical development program for idelalisib currently includes six ongoing or completed Phase 3 clinical trials for B-cell cancers. Additional information about clinical studies of idelalisib and Gilead’s investigational cancer agents can be found at www.clinicaltrials.gov.
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.
- 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 percent 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.
- Most common adverse reactions (incidence ≥20 percent; all grades) in clinical studies, when used alone or in combination with rituximab, were diarrhea, pyrexia, fatigue, nausea, cough, pneumonia, abdominal pain, chills, and rash.
- Most frequent serious adverse reactions (SAR) in clinical studies in combination with rituximab 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 frequent SAR in clinical studies when used alone were pneumonia (15 percent), diarrhea (11 percent) and pyrexia (9 percent); SAR were reported in 50 percent of patients and 53 percent of patients discontinued or interrupted therapy due to adverse reactions.
- Most common lab abnormalities (incidence ≥30 percent; all grades) in clinical studies were neutropenia, hypertriglyceridemia, hyperglycemia, and ALT/AST elevations.
- 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
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
possibility of unfavorable results from clinical trials evaluating
Zydelig for the treatment of iNHL and CLL, including in combination with
existing treatment regimens. Gilead may also be unable to enroll
patients in future studies and may need to modify or delay these studies
or perform additional studies. 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
U.S. full prescribing information, including BOXED WARNING for Zydelig is available at www.gilead.com.
Zydelig is a registered trademark of
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.
Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936
Nathan Kaiser, 650-522-1853