FDA Grants Priority Review to Darzalex Combo for Transplant-eligible Patients

The U.S. Food and Drug Administration (FDA) has granted Priority Review to the supplemental Biologics License Application (sBLA) of Darzalex (daratumumab) in combination with standard pre-transplant therapy for the treatment of patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant (ASCT).

The sBLA seeking the approval of Darzalex in combination with Velcade (bortezomib), thalidomide and dexamethasone (collectively known as VTd) was submitted by Janssen, Genmab‘s licensing partner, to the FDA in March.

Darzalex is an antibody designed to recognize and block the activity of CD38, a protein found on the surface of multiple myeloma cells, to prevent cancer cells’ growth and eliminate them. It was originally developed by Genmab, and licensed to Janssen in August 2012.

The sBLA submission was based on data from the open-label, multicenter CASSIOPEIA Phase 3 trial (NCT02541383). The study was designed to test the effects of Darzalex in combination with standard pre-transplant therapy in a group of patients with multiple myeloma who had not received any prior treatment but were eligible for an ASCT.

The trial, which enrolled 1,085 patients, is being conducted in two parts. In part one, researchers are testing whether adding Darzalex to standard VTd improves the chances of cancer eradication, compared to VTd alone. In this part, treatment is given as preparation for the stem cell transplant, and then as a consolidation of the transplant.

In part two, all patients who responded will be reassigned to receive either maintenance therapy with Darzalex every eight weeks for up to two years, or will be kept on observation with no further treatment.

In October 2018, Genmab announced topline data from the first phase of the trial, showing that adding Darzalex to standard pre-transplant therapy increased patients’ chances of seeing their cancer disappear following a stem cell transplant from 20.3% to 28.9%.

During the American Society of Clinical Oncology (ASCO) Annual Meeting, recently held in Chicago, the company announced more details regarding the topline data of CASSIOPEIA.

In an oral presentation titled, “Phase 3 randomized study of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 1 results,” Genmab showed that at a median follow-up of 18.8 months, a higher percentage of patients receiving Darzalex plus VTd remained alive and without signs of cancer progression, compared to those receiving VTd alone (92.7% versus 84.6%).

The company also announced that a higher proportion of patients treated with Darzalex in combination with VTd achieved a status of minimal residual disease (MRD, very low number of cancer cells remaining after treatment), compared to those treated with VTd alone (63.7% versus 43.5%), which was consistent with data reported last year.

Two additional poster presentations on CASSIOPEIA also took place during the meeting.

The first, “Stem cell (SC) yield and transplantation results from transplant-eligible newly diagnosed multiple myeloma (TE NDMM) patients (pts) receiving daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) in the phase 3 CASSIOPEIA study,” showed that stem cell isolation was feasible in patients treated with Darzalex plus VTd, allowing them to successfully undergo ASCT.

The second, “Efficacy of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) in transplant-eligible newly diagnosed multiple myeloma (TE NDMM) based on minimal residual disease (MRD) status: Analysis of the CASSIOPEIA trial,” showed that in patients receiving Darzalex in combination with VTd, higher MRD-negative rates were associated with longer periods without disease worsening and better clinical outcomes.

The trial is being sponsored by Janssen, the French Intergroupe Francophone du Myelome (IFM) together with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON).

“Thanks to the strong collaborative effort of IFM, HOVON, and Janssen, should the U.S. FDA approve this sBLA, patients in the United States newly diagnosed with multiple myeloma who are eligible candidates for ASCT may one day also be able to include Darzalex in combination with VTd in their treatment regimen,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.

The designation of Priority Review is given by the FDA to drugs that treat a serious medical condition and provide significant advantages to currently available treatments.

The FDA has signed a Prescription Drug User Fee Act (PDUFA), which allows the federal agency to collect fees from drug manufacturers to expedite the drug approval process, with a target date of Sept. 26, 2019. By then, the FDA must come to a decision on whether Darzalex should be approved for this indication.