EMA issues safety guidance for Gilead's Zydelig in wake of patient infections

Dive Brief:

• The European Medicines Agency (EMA) has issued new safety guidance for the use of Gilead's cancer drug Zydelig, after an increase in the number of adverse events, including deaths, was reported in several clinical trials combining Zydelig with other drugs. 
• Gilead had previously announced it was halting six clinical trials for Zydelig, including the three trials flagged in the EMA's initial review. 
• According to the new guidelines, patients are to be treated with antibiotics while receiving Zydelig. This aims to prevent a lung infection called Pneumocystisjirovecii pneumonia. The regulator also recommended monitoring of white blood cell levels and for signs of infection. 

Dive Insight:

Zydelig was approved in the E.U. in September 2014, and has been used since then for treatment of follicular lymphoma and as part of combo therapy with Roche's Rituxan (rituximab) for treatment of chronic lymphocytic leukemia (CLL). However, the latest reports may have put the development program for additional indications at risk—at least for the short term.
When the FDA approved the drug in July 2014 under an expedited review process, the approval required a black box warning on the potential for infection-related deaths. Specifically, the label warns of:

• Fatal and/or serious hepatotoxicity occurred in 14% of Zydelig-treated patients. 
• Fatal and/or serious and severe diarrhea or colitis occurred in 14% of Zydelig-treated patients. 
• Fatal and serious pneumonitis can occur in Zydelig-treated patients.
• Fatal and serious intestinal perforation can occur in Zydelig- treated patients across clinical trials. 

The PRAC is continuing its investigation in order to solidify its guidance concerning the use of Zydelig.
It should be noted, however, that the three trial included in the EMA's safety review used Zydelig in a different manner from its current authorization.
Zydelig has had less than stellar sales since its approval in summer 2014. Last year, total sales were $132 million. Gilead has other drugs in its oncology pipeline, but none that are as far along as Zydelig.