– Results Describing Long-Term Safety and Disease Control Presented at the 56th American Society of Hematology Annual Meeting –
San Francisco, December 10, 2014 – 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 the safety profile for idelalisib (Zydelig®) in 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).
In Europe, idelalisib is indicated in combination with rituximab for the treatment of adult patients with CLL who have received at least one prior therapy; or as first-line treatment in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy. Idelalisib has also been approved as a monotherapy for the treatment of adult patients with follicular lymphoma (FL) that is refractory to two prior lines of treatment.1
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.2-4 Relapse commonly occurs after initial chemo-immunotherapy5,6 and many patients with relapsed disease are unable to tolerate chemotherapy, which may limit their treatment options.7,8
“The results presented this week demonstrate the long-term benefit of idelalisib 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 idelalisib, 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 iNHL9
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 small lymphocytic lymphoma (SLL; n=17) subgroups was 10.8 months and 12.5 months, 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)10 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.
Idelalisib 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, idelalisib blocks several cellular signaling pathways that drive B-cell viability.11
On July 23, 2014, idelalisib received accelerated approved 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.12 On September 19, 2014, the European Commission granted marketing authorization for idelalisib 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 chemo-immunotherapy.13
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 EU Safety Information1
Contraindications: Hypersensitivity to the active substance or to any excipients listed in the idelalisib summary of product characteristics.
Special warnings and precautions for use: The summary of product characteristics of co-prescribed medicinal products should be consulted before starting therapy with idelalisib.
Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of Grade 3 and 4 (> 5 x ULN) have been observed in clinical studies of idelalisib. These laboratory findings were generally observed within the first 12 weeks of treatment, were generally asymptomatic, and were reversible with dose interruption. Most patients resumed treatment at a lower dose without recurrence. ALT, AST, and total bilirubin must be monitored in all patients every 2 weeks for the first 3 months of treatment, then as clinically indicated. If Grade 2 or higher elevations in ALT and/or AST are observed, patients must be monitored weekly until the values return to Grade 1 or below.
Diarrhoea / colitis
Cases of severe drug-related colitis occurred relatively late (months) after the start of therapy, sometimes with rapid aggravation, but resolved within a few weeks with dose interruption and additional symptomatic treatment (e.g., anti-inflammatory agents such as enteric budesonide).
There is very limited experience from the treatment of patients with a history of inflammatory bowel disease.
Cases of pneumonitis have been reported in clinical studies with idelalisib. Patients presenting with serious lung events that do not respond to conventional antimicrobial therapy should be assessed for drug-induced pneumonitis. If pneumonitis is suspected, idelalisib should be interrupted and the patient treated accordingly. Treatment must be discontinued for moderate or severe symptomatic pneumonitis.
Idelalisib exposure may be reduced when co-administered with CYP3A inducers such as rifampicin, phenytoin, St. John’s wort (Hypericum perforatum), or carbamazepine. Since a reduction in idelalisib plasma concentrations may result in decreased efficacy, co-administration of idelalisib with moderate or strong CYP3A inducers should be avoided.
The primary metabolite of idelalisib, GS-563117, is a strong CYP3A4 inhibitor. Thus, idelalisib has the potential to interact with medicinal products that are metabolized by CYP3A, which may lead to increased serum concentrations of the other product. When idelalisib is co-administered with other medicinal products, the Summary of Product Characteristics (SmPC) for the other product must be consulted for the recommendations regarding co-administration with CYP3A4 inhibitors. Concomitant treatment of idelalisib with CYP3A substrates with serious and/or life-threatening adverse reactions (e.g., alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, triazolam) should be avoided and alternative medicinal products that are less sensitive to CYP3A4 inhibition should be used if possible.
Intensified monitoring of adverse reactions is recommended in patients with impaired hepatic function as exposure is expected to be increased in this population, in particular in patients with severe hepatic impairment. No patients with severe hepatic impairment were included in clinical studies of idelalisib. Caution is recommended when administering idelalisib in this population.
Idelalisib has not been studied in patients with chronic active hepatitis including viral hepatitis. Caution should be exercised when administering idelalisib in patients with active hepatitis.
Women of childbearing potential
Women of childbearing potential must use highly effective contraception while taking idelalisib and for 1 month after stopping treatment. Women using hormonal contraceptives should add a barrier method as a second form of contraception since it is currently unknown whether idelalisib may reduce the effectiveness of hormonal contraceptives.
[Only for 100 mg strength]
Idelalisib contains the azo coloring agent sunset yellow FCF (E110), which may cause allergic reactions.
For the Summary of Product Characteristics, please visit www.ema.europa.eu.
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 idelalisib 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.
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
Date of preparation: December 2014
Job code: IDE/IHQ/14-11//1281
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4.What you need to know about non-Hodgkin lymphoma. National Cancer Institute. September 2007.
5. Brown JR. The treatment of relapsed refractory chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2011;2011:110-8. doi: 10.1182/asheducation-2011.1.110.
6. Salles GA. Clinical Features, Prognosis and Treatment of Follicular Lymphoma. American Society of Hematology Education Program Book. 2007;2007:216-225.
7. Furman RR et al. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2014;370:997-1007.
8. Gopal AK et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008-18.
9. Gopal AK et al. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). [ASH abstract 1708; Session 623; Date: December 7, 2014; Time: 17:30-19:00].
10. Sharman JP et al. Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors. [ASH abstract 330; Session 642; Date: December 8, 2014; Time: 08:15].
11. Lannutti BJ et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 2011;117:591-4.
12. FDA Press Release. FDA approves Zydelig for three types of blood cancers. July 2014. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm406387.htm. Accessed on October 31, 2014.
13. Gilead Press Release. European Commission Grants Marketing Authorization for Gilead’s Zydelig® (Idelalisib) for the Treatment of Chronic Lymphocytic Leukemia and Follicular Lymphoma. September 2014. Available at: http://www.gilead.com/news/press-releases/2014/9/european-commission-grants-marketing-authorization-for-gileads-zydelig-idelalisib-for-the-treatment-of-chronic-lymphocytic-leukemia-and-follicular-lymphoma. Accessed on October 31, 2014.