On July 8, the EMA’s Pharmacovigilance Risk Assessment Committee completed its review of the blood cancer drug and allowed the drug to continue to be marketed because its use outweigh any risks. The regulatory review was prompted after concerns were raised in March over safety after some patients suffered adverse side effects including deaths. Following the European concern, Gilead halted six trials it was conducting.
In the EU, Zydelig is authorized for the treatment of chronic lymphocytic leukemia in certain patients. For those patients, the drug is used in combination with rituximab, the PRAC said. Zydelig is also approved for use in a type of non-Hodgkin’s lymphoma called follicular lymphoma where it is used on its own.
With its approval, the EMA committee provided new recommendations for use to manage the potential problems. Patients taking the drug should be given antibiotics to prevent Pneumocystis jirovecii pneumonia during and shortly after treatment. Additionally, the committee said patients should be monitored and have their white blood cell counts tested before treatment begins. Low white blood cell counts can increase the risk of infection and the committee said the drug should not be administered if patients show signs of infection.
“The PRAC now concludes that Zydelig can again be initiated in these patients provided they cannot take any alternative treatment and that the measures agreed to prevent infection are followed,” the committee said in their ruling.
The drug went under the microscope of the regulatory committee following reports of harmful side effects and infections in three clinical trials where Gilead’s drug was being used in combination with other cancer therapies. The clinical trials involved patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. However, the study in chronic lymphocytic leukemia investigated combinations of medicines that are currently not approved, the European Medicines Agency said at the time. Additionally, the EMA said the studies in non-Hodgkin lymphoma included patients with disease characteristics different from those covered by the currently approved indications.
Zydelig gained regulatory approval in the United States in 2014 for three blood cancers—for relapsed chronic lymphocytic leukemia in combination with Roche (RHHBY)'s Rituxan (rituximab); to treat patients with relapsed follicular B-cell non-Hodgkin lymphoma; and relapsed small lymphocytic lymphoma. In Europe, Zydelig for the treatment of chronic lymphocytic leukemia in combination with Rituxan was approved on its own for treating follicular lymphoma, type of non-Hodgkin lymphoma.
In the United States, Zydelig carries a Boxed Warning regarding serious and fatal toxicities including liver toxicity, diarrhea and colon inflammation (colitis), lung inflammation (pneumonitis) and intestinal perforation, the FDA said when it approved the drug.