The European Medicines Agency's (EMA's) Pharmacovigilance Risk Assessment Committee (PRAC) has completed its review of idelalisib (Zydelig, Gilead Sciences) and confirmed that the benefits outweigh the risks.
However, the PRAC did confirm that treatment with idelalisib carries an increased risk for serious infections, including Pneumocystis jirovecii pneumonia, and it has updated recommendations on how to manage this risk. The committee recommends that all patients treated with idelalisib should be given prophylactic antibiotics.
A first-in-class kinase inhibitor, idelalisib was approved in the United States in July 2014 for the treatment of relapsed chronic lymphocytic leukemia (CLL), relapsed follicular B-cell non-Hodgkin's lymphoma, and relapsed small lymphocytic lymphoma (SLL).
A few months later, it was approved in Europe for indications similar, but not identical, to those in the United States.
The EMA began its review of the drug in March 2016, in response to an increased rate of reported serious adverse events, including deaths, which were primarily due to infections.
These events were observed in three clinical trials that were evaluating idelalisib in combination with other therapies.
The clinical trials involved patients with CLL and indolent non-Hodgkin's lymphoma. However, the clinical trial in CLL investigated drug combinations that are currently not approved, and the studies in non-Hodgkin's lymphoma included patients with disease characteristics that differ from those covered by the currently approved indications.
Right after the EMA announced its review, Gilead Sciences halted six clinical trials that were also using idelalisib in combination with other cancer drugs, and also because of a higher rate of serious and even lethal adverse events.
The six clinical trials in question involved SLL, CLL, and indolent non-Hodgkin's lymphoma. At that time, the US Food and Drug Administration cautioned that clinicians should not prescribe idelalisib for patients with previously untreated CLL.
The PRAC has noted that even though studies did not use drugs according to authorized use, the risk for serious infection is considered relevant to the authorized use, and they recommend that all treated patients be given antibiotics to prevent P jirovecii pneumonia.
Antibiotics should be administered during treatment and for up to 2 to 6 months after treatment has ended. Patients should also be closely monitored for infection, and idelalisib should also not be started in patients with a generalized infection.
At the beginning of the review, the PRAC had also advised that as a precaution, idelalisib should not be started in patients with previously untreated CLL who carry the 17p deletion or TP53 mutations. But now the PRAC has concluded that treatment can again be initiated in these patients, with the stipulation that they do not receive any alternative treatment and that measures much be taken to prevent infection.
The PRAC's recommendations will now be passed to the EMA's Committee for Medicinal Products for Human Use for adoption of the Agency's final position.
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