Gilead Sciences, announced that the US Food and Drug Administration (US FDA) has approved Zydelig (idelalisib) 150 mg tablets for the treatment of three B-cell blood cancers. Zydelig is indicated in combination with rituximab for patients with relapsed chronic lymphocytic leukaemia (CLL) for whom rituximab alone would be considered appropriate therapy and 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. Accelerated approval was granted for FL and SLL based on overall response rate. Zydelig is a first-in-class inhibitor of PI3K delta, a protein that is over-expressed in many B-cell malignancies and plays a role in the viability, proliferation and migration of these cancer cells.

“Zydelig is a much needed new treatment option for appropriate patients with CLL and these indolent lymphomas who have experienced relapses and have limited, if any, treatment options,” said Bruce Cheson, MD, Professor of Medicine, Head of Hematology and Director of Hematology Research at Lombardi Comprehensive Cancer Center at Georgetown University, and a principal investigator on the Zydelig pivotal Phase 3 trial in CLL. “In clinical studies among patients with relapsed CLL, FL and SLL, Zydelig produced strong responses, including a significant improvement in progression-free survival in CLL. I believe it helps fill a significant unmet need for these patients.”

Over 200,000 Americans are living with CLL, FL or SLL, slow-growing incurable blood cancers that can lead to life-threatening complications such as anemia, serious infection and bone marrow failure requiring treatment. Relapse commonly occurs after initial chemoimmunotherapy and many patients with relapsed CLL, FL or SLL are unable to tolerate chemotherapy, which may limit their treatment options.

“Gilead is committed to the development of novel cancer therapies and we are proud to have this opportunity to make a difference in the lives of people living with these cancers,” said John C. Martin, PhD, chairman and chief executive officer, Gilead Sciences. “We extend our thanks to the many physicians and patients who participated in Zydelig clinical trials, and are now focused on making this medicine available to patients as expeditiously as possible.”

The product’s approval in CLL is supported primarily by data from a randomised, placebo-controlled Phase 3 trial (Study 116) of Zydelig plus rituximab in 220 patients with relapsed CLL who were not able to tolerate standard chemotherapy. Study 116 was stopped early in October 2013 by an independent Data Monitoring Committee due to a highly statistically significant benefit in progression-free survival (PFS) in the Zydelig arm as compared to those receiving rituximab alone (hazard ratio = 0.18 (95 per cent CI: 0.10, 0.32), p<0.0001). Median PFS was not reached in the Zydelig plus rituximab arm (95 percent CI: 10.7 months, NR) and was 5.5 months in the placebo plus rituximab arm (95 per cent CI: 3.8, 7.1). The FDA granted Zydelig a Breakthrough Therapy designation for relapsed CLL, a designation granted to drug candidates that may offer major advances in treatment over existing options.

Zydelig’s accelerated approval in FL and SLL, two types of indolent non-Hodgkin lymphoma, is supported by data from a single-arm Phase 2 study (Study 101-09) of Zydelig monotherapy in patients refractory to rituximab and alkylating-agent-containing chemotherapy (FL: n=72; SLL: n=26). In the study, Zydelig achieved an overall response rate of 54 per cent (range: 42-66 per cent) and 58 per cent (range: 37-77 per cent), respectively, in FL and SLL patients. Of the responses seen in FL patients, 8 per cent (n=6) were complete responses; all 15 responses in SLL patients were partial responses. The median duration of response was 11.9 months in SLL patients (range: 0.0, 14.7 months) and median duration of response was not reached in FL patients (range: 0.0, 14.8 months). Improvement in patient survival or disease related symptoms has not been established in these indications. Results of Study 116 and Study 101-09 were published in The New England Journal of Medicine in March 2014.

FDA has also approved a risk evaluation and mitigation strategy (REMS) for Zydelig. The purpose of the Zydelig REMS is to inform healthcare providers of the serious risks of hepatotoxicity, severe diarrhoea, colitis, pneumonitis and intestinal perforation. Additional information about the Zydelig REMS Programme can be found.

Gilead is committed to ensuring that patients with CLL, FL and SLL can access Zydelig and has launched Zydelig AccessConnect to provide assistance to appropriate patients who are uninsured, underinsured or who need financial assistance to pay for the medicine. The Programme consists of an integrated offering of support services for patients and providers, including:

Access to dedicated case specialists to help patients and their providers with insurance-related needs, including identifying coverage options.

The Zydelig Co-pay Coupon Programme, which provides co-pay assistance for eligible patients with private insurance who need assistance paying for out-of-pocket medication costs. Most patients will pay no more than $5 per monthly co-pay.

Gilead will provide support to independent non-profit organisations that provide assistance for eligible federally-insured and privately-insured patients who need help covering out-of-pocket medication costs.

Eligible patients who have been prescribed Zydelig for an FDA-approved indication and who are experiencing insurance coverage delays greater than five business days may receive a 30-day supply of Zydelig while coverage is established.

Patients enrolled into Zydelig AccessConnect will receive the support needed to connect with a specialty pharmacy based on the policies of their individual health plan.

The AccessConnect Patient Assistance Programme will provide Zydelig at no charge for eligible patients with no other insurance options.

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. Zydelig is indicated in combination with rituximab for the treatment of relapsed chronic lymphocytic leukaemia in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities and as monotherapy for relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic lymphoma (SLL) in patients who have received at least two prior therapies. The FL and SLL indications were granted accelerated approval based on overall response rate; improvement in patient survival or disease related symptoms has not been established in these indications. Continued approval for these indications is contingent upon verification of clinical benefit in confirmatory trials. Zydelig is available as 150 mg and 100 mg tablets, administered orally twice-daily; 150 mg is the recommended starting dose.