Janssen has submitted an application to Japanese authorities seeking the approval of Darzalex (daratumumab) — in combination with standard Revlimid (lenalidomide) and dexamethasone — for the treatment of newly diagnosed multiple myeloma patients ineligible for high-dose chemotherapy and stem cell transplant.
The supplemental new drug application, which will be considered under priority review, is based on data from the Phase 3 MAIA clinical trial (NCT02252172), where the triple combination reduced the risk of disease progression or death by 45% compared with standard care alone, and doubled the number of patients with a complete response.
Darzalex, discovered by Genmab and developed and commercialized by Janssen, is an antibody that targets a surface protein called CD38, which is found in high numbers in multiple myeloma cells. By binding CD38, Darzalex causes myeloma cells to die.
MAIA included 737 multiple myeloma patients across more than 210 centers in North America, Europe, Australia, and Israel. The participants were newly diagnosed, had never been treated, and were not eligible for a stem cell transplant.
They were randomly assigned one of two regimens: Darzalex in combination with Revlimid and dexamethasone, or Revlimid and dexamethasone only. Its main goal was to determine if Darzalex extended the time without disease progression. Secondary measures included the duration of responses, the number of complete responses, overall survival, and quality of life assessments.
After a median follow-up of 28 months, the researchers found that the Darzalex triple combination lowered the risk of disease progression or death by 45% compared with standard treatment.
While more than half of patients on Darzalex were still alive and progression-free at the time of the analysis, those in the control group lived for a median of only 31.9 months without their disease worsening.
Darzalex also increased the number of very good or better partial responses compared with standard treatment — 79.3% versus 53.1% — and nearly doubled complete responses, 47.6% versus 24.7% respectively.
The most common serious or life-threatening side effects in the Darzalex group were low levels of neutrophils and white blood cells, pneumonia, and anemia. Infusion-related reactions occurred in 41% of patients, 3% of which were severe or life-threatening.
Janssen is also seeking the approval of Darzalex for a similar indication in the U.S. and Europe. In the U.S., the application is being reviewed under the U.S. Food and Drug Administration’s Real-Time Oncology Review pilot program.
“This marks the third major regulatory submission based on the MAIA data, following similar submissions earlier this year in the U.S. and Europe,” Jan van de Winkel, PhD, Genmab’s CEO, said in a press release. “The regulatory approvals will make daratumumab plus lenalidomide and dexamethasone a viable option for newly diagnosed multiple myeloma patients in these three major markets.”