— Results Describing Long-Term Safety and Disease Control Presented at the 56th American Society of Hematology Annual Meeting –
SAN FRANCISCO–(BUSINESS WIRE)–Gilead Sciences, Inc. (NASDAQ: GILD) today announced long-term follow-up results from the registration studies further describing the duration of response, progression-free survival (PFS) and safety profile for Zydelig® (idelalisib) in relapsed patients with chronic lymphocytic leukemia (CLL) and two types of indolent non-Hodgkin lymphoma (iNHL). The findings are being presented this week at the Annual Meeting of the American Society of Hematology (ASH).
Zydelig is indicated in the United States as monotherapy for patients with relapsed follicular B-cell non-Hodgkin lymphoma (FL) and small lymphocytic lymphoma (SLL) who have received at least two prior systemic therapies, and in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. Accelerated approval was granted for FL and SLL based on overall response rate; improvement in patient survival has not been established.
Indolent NHL and CLL are slow-growing, incurable blood cancers occurring typically in older individuals and can lead to life-threatening complications such as anemia, serious infection and bone marrow failure. Relapse commonly occurs after initial chemoimmunotherapy and many patients with relapsed disease are unable to tolerate chemotherapy, which may limit their treatment options.
“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 Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “As part of our ongoing effort to further define the safety and efficacy profile of Zydelig, we are continuing to pursue long-term follow-up studies and larger Phase 2 and Phase 3 clinical trials in combination with existing treatment regimens in both relapsed and first-line CLL and iNHL.”
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 (June 2014), 72 patients (58 percent) had responded to therapy, including 12 (10 percent) who have achieved a complete response—an increase from seven (six percent) complete responses reported initially and which were published earlier this year in The New England Journal of Medicine. The median duration of response for all patients at the most recent data cutoff was 12.5 months. The median duration of response among patients in the FL (n=40) and SLL (n=17) subgroups was 10.8 months and 12.5, respectively.
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.
On July 23, 2014, Zydelig received accelerated approval from the U.S. Food and Drug Administration as monotherapy for patients with relapsed FL or SLL who have received at least two prior systemic therapies, and full approval in combination with rituximab for patients with relapsed CLL for whom rituximab alone would be considered appropriate therapy due to comorbidities. On September 19, 2014, the European Commission granted marketing authorization for Zydelig as monotherapy in FL patients who are refractory to two prior lines of treatment, and in combination with rituximab for CLL patients who have received at least one prior therapy, or in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemoimmunotherapy.
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
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. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.
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 September 30, 2014, 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.