Daratumumab and hyalyronidase-fihj (Darzalex Faspro, Janssen Pharmaceutical), a new subcutaneous formulation of daratumumab, has been approved by the FDA in 4 regimens across 5 indications in patients with multiple myeloma, including those with newly diagnosed, transplant-ineligible multiple myeloma, and relapsed or refractory multiple myeloma.

The drug is co-formulated with recombinant human hyaluronidase PH20 and will be available as soon as the week of May 11, according to Janssen Pharmaceutical. The intravenous formulation will also remain available.

“The approval of Darzalex Faspro marks an important milestone which will help make a positive difference in the lives of patients who depend on this effective therapy,” said Paul Giusti, president and CEO of the Multiple Myeloma Research Foundation, in a prepared statement.

The FDA’s approval is based on data from phase 3 of the COLUMBA trial and phase 2 of the PLEIADES trial.

The COLUMBA study included 522 patients with multiple myeloma who had received at least 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or whose disease was refractory to both a PI and an IMiD. In the arm receiving the subcutaneous formulation, patients received a fixed dose weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks for cycles 7 and on.

In the COLUMBA trial, the overall response rate was noninferior for patients taking the subcutaneous daratumumab formulation as monotherapy, compared to those taking the intravenous formulation. The investigators also observed fewer systemic absolute risk reductions among patients receiving the subcutaneous formulation.

The PLEIADES study enrolled more than 240 adults with multiple myeloma, including 67 with newly diagnosed disease. They were treated with 1800 mg of the subcutaneous daratumumab formulation in combination with bortezomib, melphalan, and prednisone. Additionally, 65 patients with relapsed or refractory disease were treated with 1800 mg of the subcutaneous formulation in combination with lenalidomide and dexamethasone.

In the second phase of the PLEIADES study, objective responses were demonstrated in combination with bortezomib, melphalan, and prednisone in the newly diagnosed, transplant ineligible patients. Objective responses were also seen in the relapsed or refractory patients who received lenalidomide and dexamethasone and who had received 1 prior line of therapy.

Based on these findings, the drug is approved in combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant, in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant, in patients with relapsed or refractory multiple myeloma who have received at least 1 prior therapy, and as monotherapy in patients who have received at least 3 prior lines of therapy.

“We are excited about the potential of this meaningful innovation in transforming the treatment experience for patients with multiple myeloma where Darzalex Faspro can be administered in approximately 3 to 5 minutes, significantly less time than intravenous Darzalex, which is given over hours,” said Mathai Mammen, MD, PhD, global head of Janssen Research & Development LLC, in a prepared statement. “Based on its favorable profile, we are accelerating the development of Darzalex Faspro and evaluating its potential in multiple ongoing studies.”


REFERENCE

US Food and Drug Administration Approves Darzalex Faspro (daratumumab and hyaluronidase-fihj), a New Subcutaneous Formulation of Daratumumab in the Treatment of Patients with Multiple Myeloma [news release]. Janssen Pharmaceuticals; May 1, 2020. https://www.janssen.com/us/sites/www_janssen_com_usa/files/darzalex_faspro_approval_press_release_final.pdf. Accessed May 6, 2020.