Other safety alerts
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| Singapore: Idelalisib and the risk of serious infections |
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The Singapore Health Sciences Authority (HSA) would like to inform healthcare professionals about the higher incidence of serious adverse events (AEs) and increased risk of death observed in patients receiving idelalisib in three Phase III clinical trials that were evaluating patient populations and/or treatment combinations which are not registered.
Idelalisib (Zydelig®, Gilead Sciences Singapore Pte Ltd) is a phosphatidylinositol 3-kinase inhibitor, registered in Singapore in February 2016. It is approved, in combination with rituximab, for the treatment of relapsed chronic lymphocytic leukaemia (CLL) in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. It is also indicated for the treatment of relapsed follicular B-cell non-Hodgkin lymphoma and relapsed small lymphocytic lymphoma in patients who have received at least two prior systemic therapies, based on overall response rates to idelalisib monotherapy.
The three Phase III clinical trials, where an increased rate of serious AEs, and increased mortality were detected, investigated the addition of idelalisib to standard therapies in first-line treatment of CLL and relapsed indolent non-Hodgkin lymphoma (iNHL). The clinical trial on CLL studied idelalisib for first-line treatment of CLL, which is not an approved use for idelasilib. The clinical trials on relapsed iNHL investigated patients with disease characteristics different from the currently approved indications or investigated idelalisib in treatment combination that is not currently approved for relapsed iNHL.
Gilead’s review of the clinical trials found an increased risk of serious AEs, including deaths, in patients receiving idelalisib compared to placebo for first-line treatment of CLL and relapsed iNHL. The majority of events were infections, which included sepsis and opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) infections. These trials have since been terminated by the company.
In March 2016, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) initiated a safety review on idelalisib in response to the findings from the Phase III clinical trials. In July 2016, PRAC concluded that the benefit-risk balance of idelalisib for its authorised use in the treatment of relapsed CLL and follicular lymphoma that is refractory to two prior lines of treatment remains positive. Although the trials reviewed for this safety concern did not evaluate idelalisib in its currently authorised patient populations or treatment combinations, the committee considered that the risk of serious infections, including PJP, associated with idelalisib remained relevant to its authorised use. The recommendations by PRAC to minimise this risk included prophylaxis for PJP and regular blood count monitoring. PRAC also recommended that idelalisib should not be initiated in patients with any generalised infection.
To date, HSA has not received any local reports of serious infections associated with the use of idelalisib. The local package insert of Zydelig® has been strengthened to include the following warnings:
• Idelalisib is not recommended for first-line treatment of CLL
• Prophylaxis for PJP should be administered to all patients throughout idelalisib treatment
• Monitor patients for CMV and discontinue idelalisib if there is evidence of infection or viraemia (positive PCR or antigen test)
• Monitor blood counts at least every two weeks for the first six months, and at least weekly in patients with neutrophil counts less than 1.0Gi/L
A Dear Healthcare Professional Letter was issued by the company in April 2016 to communicate the safety concerns to healthcare professionals.
Healthcare professionals are advised to take into consideration the above safety information when prescribing idelalisib and to monitor their patients for signs and symptoms of infections throughout idelalisib treatment.
Please refer to the following website in HSA for details:
http://www.hsa.gov.sg/content/hsa/../idelalisib-and-theriskofseriousinfections.html
In Hong Kong, there are two registered pharmaceutical products containing idelalisib, namely Zydelig Tablets 100mg (HK-64093) and Zydelig Tablets 150mg (HK-64094). Both products are prescription only medicines and are registered by Gilead Sciences Hong Kong Limited (Gilead). News on the risk of serious adverse effects including deaths in patients receiving idelalisib was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 12 March 2016, with the latest update posted on 17 September 2016. Letters to inform local healthcare professionals on the above risk were issued on 14 March 2016. Gilead had also issued letters to inform local healthcare professionals and had submitted application to update the package inserts of the products to include information on the above risk. So far, the Department of Health (DH) has not received application for the concerned clinical trials to be conducted in Hong Kong. There is one adverse drug reaction case after receiving idelalisib, which was not related to infection. DH will continue to remain vigilant on the development of safety of idelalisib.
Ends/ Wednesday, December 21, 2016
Issued at HKT 17:00
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