The Scottish Medicines Consortium Approves Gilead’s Zydelig® q (Idelalisib) for the Treatment of Follicular Lymphoma That Is Refractory to Two Prior Lines of Treatment in Adult Patients

Foster City, CA, 11 May 2015 – Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the Scottish Medicines Consortium (SMC) has approved Zydelig (idelalisib) – a new first-in-class oral agent indicated as monotherapy – for adult patients with follicular lymphoma (FL) that are refractory to two prior lines of treatment, the most common type of indolent non-Hodgkin lymphoma (iNHL).

This decision follows the SMC approval of idelalisib in combination with rituximab for the treatment of adult patients with relapsed CLL who are unsuitable for chemotherapy and treatment naïve patients with 17p deletion or TP53 mutation who are unsuitable for chemo-immunotherapy, in March this year.

Tony Gavin, Chief Executive at Leukaemia Care said: “This decision by the SMC is great news for people living with follicular lymphoma in Scotland, and we are thrilled that patients who previously had limited treatment options now have access to idelalisib. We are also greatly encouraged by the SMC’s new approach to reviewing drugs for rare diseases, and are pleased to have been consulted as part of this new ‘ Patient and Clinical Engagement’ process,  to be able to provide our, and our patients,  perspectives on the acknowledged real-life benefits  this novel agent can bring to patients and their families.”

FL is the most common subtype of iNHL, a group of largely incurable, slow-growing cancers that start in the lymph nodes or the lymphatic system.1 In the UK, there are an estimated 1,890 new cases of FL each year with 849 people diagnosed with FL in 2012.2 FL accounts for around one fifth of all diagnosed cases of NHL and more than 12,000 people are diagnosed with NHL each year.3 In 2012, 1,068 new cases of NHL were noted in Scotland[i], of these 19% are expected to be FL (203 cases).3 FL can lead to life-threatening complications, such as anaemia, serious infection and bone marrow failure requiring treatment.5,6

Dr Angus Broom, Consultant Haematologist, Western General Hospital, Edinburgh said: “It is welcome news that idelalisib is now available for patients in Scotland, as improving quality of life is one of the main goals in the treatment of FL. Access to this treatment offers patients with FL a new option, for those patients unsuitable for chemotherapy.”

The SMC’s decision on idelalisib for the treatment of FL is supported primarily by data from a single-arm Phase 2 study (Study 101-09) of idelalisib monotherapy in 125 iNHL patients refractory to rituximab and alkylating-agent-containing chemotherapy.  In the 72 patients with FL in this study, idelalisib achieved an overall response rate of 54 percent and the median duration of response was not reached (range: 0.0, 14.8+ months).  Results of Study 101-097 were published in The New England Journal of Medicine in March 2014.

Adverse drug reactions (including Grade ≥3) reported in patients with FL receiving idelalisib included infections, neutropenia, pneumonitis, diarrhea/colitis, increased transaminase (indicator of liver function), rash and pyrexia.8

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

Further details on the SMC’s decision can be found here www.scottishmedicines.org.uk

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.

Important Safety Information8

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 commercialises 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.

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 idelalisib over other therapies and may therefore be reluctant to prescribe the product.  Further, additional studies of idelalisib may produce unfavourable results.  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 June 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.

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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: May 2015

Job Code: IDE/UK/15-04/CI/1082

1. Lymphoma Association. Follicular Lymphoma. Available at http://www.lymphomas.org.uk/sites/default/files/pdfs/Follicular-lymphoma.pdf. Accessed June, 2014.
2. Haematological Malignancy Research Network. Patient’s age and treatment for haematological malignancy: a report from the Haematological Malignancy Research Network (HMRN). June 2014.
3. Cancer Research UK. Non-Hodgkin lymphoma incidence statistics. Available at: http://www.cancerresearchuk.org/cancer-info/cancerstats/types/nhl/incidence/uk-nonhodgkin-lymphoma-incidence-statistics. Accessed: May 2015
4. ISD Scotland. Cancer statistics: non-Hodgkin’s lymphoma. 2014. Available at: http://www.isdscotland.org/Health-Topics/Cancer/Cancer-Statistics/Non-Hodgkins-Lymphoma/index.asp?Co=Y Accessed: October 2014.
5. 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.
6. National Cancer Institute(NCI). What you need to know about non-Hodgkin lymphoma. Available at http://www.cancer.gov/cancertopics/wyntk/non-hodgkin-lymphoma.pdf Accessed September, 2014.
7. Gopal AK et al. PI3K? inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med 2014; 370:1008-1018.
8. Zydelig Summary of Product Characteristics (100 & 150mg film-coated tablets) – March 2015.

Understanding FL

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