The European Commission (EC) has granted marketing authorization for a split dosing regimen for daratumumab (Darzalex®).
The approval provides healthcare professionals with the option to split the first infusion of daratumumab over 2 consecutive days.
“We are hopeful that the availability of this more flexible dosing option will make the first infusion of Darzalex more convenient for European multiple myeloma patients,” said Jan van de Winkel, PhD, chief executive officer of Genmab, which licensed daratumumab to Janssen Biotech, Inc.
Daratumumab is currently EC-approved for the following indications:
- For use in combination with bortezomib, melphalan, and prednisone to treat adults with newly diagnosed multiple myeloma (MM) who are ineligible for autologous stem cell transplant
- For use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adults with MM who have received at least one prior therapy
- As monotherapy for adults with relapsed and refractory MM whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on their last therapy.
The EC’s approval of a split dosing regimen for daratumumab was based on data from the phase 1b EQUULEUS trial (MMY1001, NCT01998971), which was sponsored by Janssen.
This trial was designed to evaluate daratumumab in combination with bortezomib-dexamethasone, bortezomib-melphalan-prednisone, bortezomib-thalidomide-dexamethasone, pomalidomide-dexamethasone, carfilzomib-dexamethasone, and carfilzomib-lenalidomide-dexamethasone.
At the 2018 ASH Annual Meeting (abstract 1970), researchers presented data from this trial in MM patients who received their first 16 mg/kg daratumumab dose as a split dose of 8 mg/kg on day 1 of cycle 1 and 8 mg/kg on day 2 of cycle 1, compared to patients who received the full 16 mg/kg dose on day 1 of cycle 1.
The researchers said they observed “virtually identical” pharmacokinetics between the dosing groups.
Cmax on the first day of cycle 1 was lower in the split-dose group than in the full-dose group. However, after patients in the split-dose group received the second 8 mg/kg dose on day 2, concentrations were similar between the groups.
The researchers said they do not expect the initial difference they observed to have any impact on clinical outcomes.
The team also pointed out that there was no increase in infusion-related reactions among patients who received the split dose.