Janssen Biotech has asked that the U.S. Food and Drug Administration to expand the label for Darzalex (daratumumab) to include its use, in combination with standard Revlimid (lenalidomide) and dexamethasone, as a first-line treatment for new multiple myeloma patients ineligible for high-dose chemotherapy and a stem cell transplant.
The company submitted the first part of a regulatory package for review under the FDA’s Real-Time Oncology Review (RTOR) pilot program. This program aims to explore a more efficient review process, so as to move treatments found safe and effective to patients more quickly.
“We are encouraged that the submission for daratumumab in combination with lenalidomide and dexamethasone has begun, with a potential for the regimen to be approved earlier for US patients,” Jan van de Winkel, PhD, chief executive officer of Genmab, said in a press release.
The submission is based on data from the MAIA Phase 3 trial (NCT02252172), where the triple combination reduced the risk of disease progression or death by 45% compared to standard of care alone, and doubled the number of patients achieving a complete response to treatment.
MAIA included 737 multiple myeloma patients across more than 210 centers in North America, Europe, Australia, and Israel. Patients, newly diagnosed, had never been treated and were not eligible for a stem cell transplant.
In the trial, they were randomly assigned Darzalex in combination with Revlimid and dexamethasone, or Revlimid and dexamethasone only (control group). Its main goal was to determine if Darzalex as an add-on treated 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.
Results presented in December showed that, after a median follow-up of 28 months, patients in the control group went for a median time of 31.9 months without disease progression , while more than half of the those given the Darzalex combination were alive progression free. Overall, this represented a 45% reduction in the risk of disease progression or death.
Darzalex’s inclusion as treatment also increased the amount of very good or better partial responses compared to standard treatment – 79.3% versus 53.1% – and nearly doubled complete responses, 47.6% versus 24.7% respectively.
More patients on the experimental combination were reported to have developed serious pneumonia, and low levels of neutrophils or white blood cells, but the preliminary analysis also suggested that Darzalex may reduce the risk of death by 22% compared to standard treatment. Primary trial data are being collected through December, and more results are needed to reach statistical significance.
Darzalex, initially discovered by Genmab and later licensed to Janssen Biotech, is an antibody that targets CD38, a surface molecule widely produced by myeloma cells.
The treatment is already approved for multiple myeloma indications, including in combination with Revlimid, an immunomodulatory medication, and the corticosteroid dexamethasone for patients who have received at least one prior therapy.