The U.S. Food and Drug Administration has approved a new dosing regimen for the multiple myeloma treatment Darzalex (daratumumab), allowing doctors to split the first infusion over two consecutive days.
The approval is based on data from the EQUULEUS Phase 1b trial (NCT01998971), where the split dosing lead to similar safety and pharmacokinetics — the way a compound is absorbed, distributed, metabolized, and excreted — at the end of weekly dosing as a single infusion.
“The first infusion of Darzalex is an important first step in a patient’s course of therapy, and this approval provides added flexibility for how patients may receive initial treatment,” Craig Tendler, MD, vice president, Clinical Development and Global Medical Affairs, Janssen Research & Development, said in a press release. “We are committed to exploring options that may improve the overall treatment experience for patients.”
Darzalex, jointly developed by Genmab and Janssen, is an antibody that targets CD38, a protein widely produced by multiple myeloma cells. When bound to its target, Darzalex not only causes cells to die directly but also activates immune-dependent processes that help eliminate cancer cells.
Currently, Darzalex is approved in the U.S. for four multiple myeloma indications, including in combination with Pomalyst (pomalidomide) and dexamethasone for patients who received at least two prior myeloma treatments. These prior treatments can include Revlimid (lenalidomide) and a proteasome inhibitor, like Kyprolis (carfilzomib), Ninlaro (ixazomib), or Velcade (bortezomib).
This approval was also based on data from EQUULEUS, a global Phase 1 trial that tested Darzalex in combination with multiple treatment regimens.
One of EQUULEUS’ arms included 80 patients who received a combination of Darzalex, Kyprolis, and dexamethasone. Among them, 10 received Darzalex’s first infusion as a single dosing, and the remaining patients were given a dose split over two consecutive days. After the first week, researchers examined Darzalex levels in the blood and determined the treatment’s safety.
The split dosing allowed for a shorter first infusion, while showing a similar pattern of infusion reactions. Infusion-related adverse events by type were also similar for both regimens.
Measures of Darzalex levels also showed that both approaches led to similar concentrations at the end of weekly dosing, indicating the treatment can be split without affecting its efficacy.
While the split dosing was tested in combination with Kyprolis and dexamethasone, the initial split-dosing is approved for any of Darzalex’s indications. This split dosing regimen is also approved in Europe and in Canada.