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Follow-up data from idelalisib (Zydelig) registrational studies in patients with chronic lymphocytic leukaemia and follicular lympho

Gilead Sciences, Inc. has 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 leukaemia (CLL) and follicular lymphoma (FL). The findings are being presented at the Annual Meeting of the American Society of Haematology (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 licensed as a monotherapy for the treatment of adult patients with FL that is refractory to two prior lines of treatment.1

FL and CLL are slow-growing, incurable blood cancers occurring typically in older individuals and can lead to life-threatening complications such as anaemia, serious infection and bone marrow failure.2-5 Relapse commonly occurs after initial chemo-immunotherapy6,7 and many patients with relapsed disease are unable to tolerate chemotherapy, which may limit their treatment options.8,9

“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 FL.”

Study 101-09 in FL10

Study 101-09 (Abstract #1708) is a single-arm Phase 2 study evaluating idelalisib monotherapy in 125 patients with previously treated FL 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 subgroup (n=40) was 10.8 months.

The most common Grade ?3 adverse events among all patients were diarrhoea/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)11 was a randomised, 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 randomised 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 diarrhoea/colitis (16 percent) and pneumonia (13 percent). Grade ?3 transaminase elevations occurred in 6 percent of patients.

About idelalisib

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 leukaemias and lymphomas, and by inhibiting the protein, idelalisib blocks several cellular signaling pathways that drive B-cell viability.12

On July 23, 2014, idelalisib 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.13 On September 19, 2014, the European Commission granted marketing authorisation 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.14

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.


1. European Medicines Agency. ZYDELIG (idelalisib) SPC. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003843/WC500175377.pdff. Accessed December 2014.

2. Chronic Lymphocytic Leukemia Treatment (PDQ). National Cancer Institute (NCI). Available at http://www.cancer.gov/cancertopics/pdq/treatment/CLL/healthprofessional/page1/AllPages. Accessed on October 31, 2014.

3. Lymphoma Association. Follicular Lymphoma. Available at http://www.lymphomas.org.uk/sites/default/files/pdfs/Follicular-lymphoma.pdf. Accessed June, 2014.

4. Adult Non-Hodgkin Lymphoma Treatment (PDQ). National Cancer Institute (NCI). Available at http://www.cancer.gov/cancertopics/pdq/treatment/adult-non-hodgkins/HealthProfessional/page1/AllPages. Accessed on October 31, 2014.

5. What you need to know about non-Hodgkin lymphoma. National Cancer Institute. September 2007.

6. 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.

7. Salles GA. Clinical Features, Prognosis and Treatment of Follicular Lymphoma. American Society of Hematology Education Program Book. 2007;2007:216-225.

8. Furman RR et al. Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2014;370:997-1007.

9. Gopal AK et al. PI3K? inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370:1008-18.

10. 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].

11. 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].

12. 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.

13. 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.

14. 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.

Source: Gilead Sciences