FDA Approves 8th Darzalex Faspro Indication for Myeloma Patients

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by Steve Bryson, PhD |

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The U.S. Food and Drug Administration (FDA) has approved Darzalex Faspro (daratumumab and hyaluronidase), in combination with Kyprolis (carfilzomib) and the corticosteroid dexamethasone, for the treatment of adults with multiple myeloma who have received one to three lines of therapy.

Darzalex Faspro is a subcutaneous, or under-the-skin, formulation of the Janssen laboratory-made therapy Darzalex (daratumumab), which is administered intravenously or into the vein. Compared with intravenous Darzalex, the subcutaneous formulation requires markedly less expertise to give safely and takes minutes rather than hours.

The new approval marks the ninth indication for Darzalex Faspro across a range of regimens, including eight for myeloma patients. It was based on data from the PLEIADES Phase 2 trial (NCT03412565), in which the proportion of patients responding to the triple combination was similar to that observed for a Darzalex-containing combo.

“Today’s approval of Darzalex Faspro, in combination with yet another widely used regimen, further substantiates the subcutaneous formulation as a foundational element in the treatment of multiple myeloma,” Craig Tendler, MD, global head of late development, diagnostics and medical affairs, hematology and oncology, at Janssen research and development, said in a press release.

“We will continue to explore the full potential of Darzalex Faspro as part of our commitment to advancing science and transforming patient outcomes in the treatment of this disease,” he added.

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Daratumumab, the active ingredient in Darzalex and Darzalex Faspro, is an antibody designed to both prevent the growth and eliminate myeloma cells by binding to a protein, called CD38, on their surface. The under-the-skin formulation also includes hyaluronidase, an enzyme that destroys components of the connective tissue, which increases the absorption of drugs and fluids injected under the skin.

The PLEIADES trial is investigating Darzalex Faspro as part of a number of standard-of-care treatment regimens for multiple myeloma patients. In addition to the Darzalex Faspro-Kyprolis-dexamethasone combination, which was tested in 66 patients who received at least one prior line of therapy, the study is evaluating three other regimens.

One uses Darzalex Faspro alone for newly diagnosed myeloma patients eligible for a stem cell transplant, while another treats people with newly diagnosed myeloma unable to receive a transplant. These patients receive a combination of Darzalex Faspro, Velcade (bortezomib), melphalan, and prednisone.

The third regime involves a combination of Darzalex Faspro plus Velcade and dexamethasone for people who failed at least one line of therapy.

Updated data from PLEIADES were presented last year at the American Society of Hematology annual meeting. The results demonstrated that, after a median follow-up of 9.2 months, 84.8% of patients who received Darzalex Faspro plus Kyprolis and dexamethasone had responded to their treatment.

These response rates were similar to those obtained when Kyprolis and dexamethasone were used in combination with intravenous Darzalex (84.3%) in the CANDOR Phase 3 trial (NCT03158688) — a trial that supported the first-ever approval of an anti-CD38 therapy in combination with Kyprolis.

Researchers also observed a very good partial response or better in 77.3% of participants.

“Data from the PLEIADES trial continue to support additional treatment combinations that can influence the course of this disease as early as after the first relapse by providing durable responses that may help to delay progression,” said Ajai Chari, MD, director of clinical research in the multiple myeloma program, and associate director of clinical research at the Mount Sinai Cancer Clinical Trials Office.

“The approval of subcutaneous daratumumab in combination with [Kyprolis and dexamethasone] will help clinicians address unmet patient needs by reducing the administration time from hours to just minutes, and reducing the frequency of infusion-related reactions,” Chari said.

The safety profile of the combination therapy was consistent with known safety profiles of similar treatment combination regimens. Serious adverse events were reported in 27% of patients who received Darzalex Faspro plus Kyprolis and dexamethasone.

The most common adverse events included upper respiratory tract infection, insomnia, fatigue, high blood pressure, diarrhea, cough, shortness of breath, headache, nausea, fever, and tissue swelling. Fatal adverse events occurred in 3% of patients.