Janssen Seeks Darzalex Approval for Certain Newly Diagnosed Multiple Myeloma Patients in Japan

Janssen Pharmaceutical has submitted an application to Japanese authorities requesting that Darzalex (daratumumab) be approved, in combination with standard therapy, to treat newly diagnosed multiple myeloma patients who cannot receive a stem cell transplant.

The supplemental new drug application (sNDA), which will be considered under a priority review, is based on data from the ALCYONE Phase 3 clinical trial (NCT02195479). That trial also was the basis of Darzalex’s approval in the U.S. and European Union for the same indication.

Darzalex, created by Genmab, and developed and commercialized by Janssen Pharmaceuticals, is a human anti-CD38 antibody. By binding CD38, a protein found in high levels at the surface of myeloma cells, Darzalex causes myeloma cells to die.

“We are extremely pleased that daratumumab in front line multiple myeloma has now been submitted in Japan. Should this submission be approved, it would bring an exciting new therapeutic option to Japanese multiple myeloma patients in need,” Jan van de Winkel, PhD, CEO of Genmab, said in a press release.

An open-label, multicenter trial, ALCYONE tested the benefits of Darzalex as an add-on treatment to standard of care — Velcade (bortezomib), melphalan, and prednisone (VMP) — in patients with newly diagnosed multiple myeloma who were not eligible for an autologous stem cell transplant.

The trial enrolled 706 patients who received VMP therapy alone or in combination with Darzalex. Treatment was given in nine cycles, each lasting five weeks. Patients in the Darzalex group then continued to receive Darzalex as maintenance therapy until disease progression.

Results showed that 18 months after starting treatment, 71.6% of patients treated with Darzalex remained alive and disease-free compared to 50.2% of those treated with VMP alone. This represented a 50% reduction in the risk of disease progression or death.

Moreover, treatment with Darzalex increased the number of patients who responded to treatment from 73.9% to 90.9%. Complete responses were nearly double in Darzalex-treated patients — 42.6% versus 24.4%.

A total of 22.3% of patients treated with Darzalex were negative for minimal residual disease — a measure that determines whether a patient still has myeloma cells in the blood or bone marrow that could lead to relapse — against 6.2% of the patients treated with standard of care alone.

Serious adverse side effects were more common in the Darzalex group (42%) than in the VMP group (33%). The most common serious side effect was pneumonia. Also, 28% of patients receiving Darzalex experienced infusion-related reactions caused by the medicine.

Darzalex also is approved in Japan, in combination with Revlimid (lenalidomide) and dexamethasone or Velcade and dexamethasone, for myeloma patients who received at least one prior therapy.