NICE Recommends Gilead’s Zydelig® (Idelalisib) for the Treatment of Chronic Lymphocytic Leukaemia

Gilead’s Targeted Therapy to be Made Available on the NHS for the Treatment of Chronic Lymphocytic Leukaemia in England and Wales

London, 24 September 2015 – Gilead Sciences’ Zydelig® (idelalisib) has today been recommended by the National Institute for Health and Care Excellence (NICE) as a treatment option in combination with rituximab for adults with chronic lymphocytic leukaemia (CLL) who have relapsed early (<24 months).1  This combination has also been recommended for untreated CLL patients with markers for aggressive disease (genetic abnormalities called 17p deletion and/or TP53 mutation).1 As assessed by the NICE Committee, this decision indicates that idelalisib plus rituximab can offer significant health-related benefits.

CLL is the most common form of adult leukaemia in the UK, affecting approximately 28,140 people.2 The disease can lead to life-threatening complications, such as anaemia, serious infection and bone marrow failure,3 and has a significant negative impact on patients’ quality of life.4

“This is great news for patients with CLL,” said Chris West, Spokesperson for Bloodwise, the UK’s biggest blood cancer charity. “Coinciding with National Blood Cancer Awareness Month, NICE’s recommendation of idelalisib is a very welcome development for adult patients with CLL in England and Wales, particularly when there is such uncertainty around the future availability of many blood cancer treatments.”

Chemo-immunotherapy is usually the first choice for treating CLL after ‘watch and wait’, however most patients eventually relapse and need further treatment. For patients with aggressive disease that relapses within 2 years of chemo-immunotherapy treatment options are very limited. Also five per cent of patients at diagnosis and up to 10% at treatment initiation5have specific genetic abnormalities, and for these patients most conventional chemo-immunotherapy treatments are not very effective and deliver poor responses with relatively short duration.6

“Idelalisib provides a much needed option for those patients with CLL in whom conventional chemotherapy-based treatment are not very effective, including when the disease relapses quickly after previous therapy and for previously untreated patients with a molecular switch (17p deletion or TP53 mutation) that prevents chemotherapy being effective,” said Professor Peter Hillmen, Consultant Haematologist, NHS Leeds Teaching Hospitals. “Previously these patients have been faced with very limited, ineffective treatment, and had a much shorter survival than other patients with CLL.  However NICE’s decision means that these patients will soon be able to access through the NHS an effective, chemotherapy-free treatment option that directly targets the leukaemia leading to improved survival.”

Idelalisib, which received Marketing Authorisation from the European Commission one year ago,7 has been available to a restricted patient population in England through the Cancer Drugs Fund since January. This decision by NICE signals idelalisib’s long-term availability for eligible patients, and  brings England and Wales in line with the NHS in Scotland, as the Scottish Medicines Consortium (SMC) approved idelalisib for use for Scottish NHS patients in March 2015.8

Gilead worked closely with NICE to provide the evidence requested to support a positive final recommendation, in line with their commitment to patients to ensure that innovative treatments are available as early as possible.

For additional safety information, see the Summary of Product Characteristics at https://www.medicines.org.uk/emc/

About Zydelig (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 signalling is active in many B-cell leukaemias and lymphomas, and by inhibiting the protein, idelalisib blocks several cellular signalling pathways that drive B-cell viability.  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 for CLL patients in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy.  Idelalisib is administered orally twice-daily and is available as 150 mg and 100 mg dose strengths. The European Commission granted Marketing Authorisation for idelalisib for the treatment of two incurable blood cancers, double refractory FL and chronic lymphocytic leukaemia (CLL) in the European Union, on 19 September 2014.9

Important Safety Information7

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.

Transaminase elevations

Elevations in ALT and 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.

Pneumonitis

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.

CYP3A inducers

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.

CYP3A substrates

The primary metabolite of idelalisib, GS-563117, is a strong CYP3A4 inhibitor.  Thus, idelalisib has the potential to interact with medicinal products that are metabolised 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.

Hepatic impairment

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.

Chronic hepatitis

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.

Excipients

Zydelig 100mg tablet contains the azo colouring agent sunset yellow FCF (E110), which may cause allergic reactions.

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. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement

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 risk that physicians and patients may not see advantages of sofosbuvir over other therapies and may therefore be reluctant to prescribe the product. In addition, pending marketing applications for sofosbuvir in other territories may not be approved in the currently anticipated timelines or at all, and marketing approval, if granted, may have significant limitations on its use. 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 Annual Report on Form 10-Q for the quarter ended March 31, 2015, 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.

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The European SmPC for idelalisib is available from the EMA website at www.ema.europa.eu

Zydelig is a registered trademark of Gilead Sciences, Inc.

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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

Date of preparation: September 2015
Job Code: ZDG/UK/15-09/CI/1686

1. National Institution for Health and Care Excellence. Final Appraisal Decision for Zydelig (idelalisib) in Chronic Lymphocytic Leukaemia. September 2015.
2. HMRN. Statistics. Available at https://www.hmrn.org/statistics/quick. Accessed September 2015
3. National Cancer Institute(NCI). Chronic lymphocytic leukemia treatment (PDQ). National Cancer Institute (NCI). Available at http://www.cancer.gov/cancertopics/pdq/treatment/CLL/Patient/page1/allpages Accessed September, 2014
4. Shanafelt TD & Kay NE. Comprehensive management of the CLL patient: a holistic approach. Hematology Am Soc Hematol Educ Program 2007:324-331.
5. Eichhorst B, et al. Chronic Lymphocytic Leukaemia: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Annals of Oncology. 26(S5): v78-84. 2015
6. Seiffert M et al. Exploiting biological diversity and genomic aberrations in chronic lymphocytic leukemia. Leuk Lymphoma 2012; 53:1023-1031.
7. Zydelig Summary of Product Characteristics (100 & 150mg film-coated tablets) – March 2015. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003843/WC500175377.pdf. Accessed September 2015.
8. Scottish Medicines Committee. Advice on Zydelig in Chronic Lymphocytic Leukaemia. March 2015. https://www.scottishmedicines.org.uk/files/advice/idelalisib_Zydelig_FINAL_February_2015_Amended_04.03.15_for_website.pdf. Accessed September 2015
9. European Medicines Agency. Available at http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003843/human_med_001803.jsp&mid=WC0b01ac058001d124. Accessed September, 2014.

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