Darzalex combo up for EU approval for multiple myeloma patients
Request covers all those newly diagnosed, regardless of transplant eligibility
Johnson & Johnson (J&J) is asking regulatory authorities in the European Union to approve a combination treatment based on the subcutaneous, or under-the-skin, formulation of Darzalex (daratumumab) for adults with newly diagnosed multiple myeloma.
Known as D-VRd, the quadruple therapy includes subcutaneous Darzalex — sold as Darzalex Faspro in the U.S. — alongside the standard VRd treatment combo of bortezomib (sold as Velcade and generics), lenalidomide (sold as Revlimid and generics), and dexamethasone.
“The potential of this daratumumab subcutaneous-based regimen to transform outcomes for people with newly diagnosed multiple myeloma is incredibly promising, and today’s submission builds on our portfolio of Phase 3 studies aimed at elevating the standard of care for all patients in the frontline treatment setting,” Edmond Chan, MD, therapeutic lead of hematology for the Europe, Middle East, and Africa region at J&J, said in a company press release.
Application includes European myeloma patients not eligible for transplant
The company had previously submitted an application asking that the D-VRd combo be approved specifically for adults with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT), a standard treatment for myeloma. That application last month received a positive recommendation from the European Medicines Agency’s Committee for Medicinal Products for Human Use.
Should the European Commission approve both regulatory requests, the D-VRd combo could be used as a first-line therapy regardless of patients’ transplant eligibility.
“While we’ve seen significant progress in multiple myeloma treatment, there continues to be a tremendous opportunity to improve frontline therapies and ensure we are providing patients with better long-term outcomes,” Chan said.
The D-VRd combo is already approved for newly diagnosed adult patients eligible for ASCT in the U.S. Earlier this month, J&J submitted a request to expand the combo’s use in the country to patients for whom a transplant was not initially planned.
Daratumumab, the active ingredient in all available Darzalex formulations, works to kill myeloma cells by targeting CD38, a protein highly produced by these cancer cells.
60% of patients given Darzalex combo had no detectable myeloma cells
J&J’s new application in the EU is based on data from a Phase 3 clinical trial called CEPHEUS (NCT03652064). That study enrolled 396 adults with newly diagnosed myeloma who weren’t eligible for or who deferred ASCT.
Participants in CEPHEUS were randomly assigned to treatment with either the D-VRd combo or the standard VRd combo. The results showed that patients given the combination with Darzalex were 43% less likely to die or experience disease progression after nearly five years.
More than 60% of patients on the quadruple combo had no detectable cancer cells, compared with nearly 40% of those given the triple combo.
The data from CEPHEUS add to the body of evidence for daratumumab [subcutaneous] in newly diagnosed multiple myeloma and, together with the results of the PERSEUS study, demonstrate the potential benefit of this quadruplet regimen for newly diagnosed patients, regardless of transplant eligibility.
The CEPHEUS study didn’t reveal any unexpected new safety issues; the most common severe to life-threatening adverse events reported with the D-VRd combo included low counts of blood cells and clotting-inducing platelets, nerve damage, diarrhea, and COVID-19.
D-VRd combo’s approval in the U.S. and approval request in the EU for newly diagnosed patients eligible for stem cell transplant were based on data from the Phase 3 PERSEUS trial (NCT03710603). That study showed that the D-VRd combo significantly lowered the risk of myeloma progression or death by 58% relative to the standard VRd.
Craig Tendler, MD, vice president of clinical development, diagnostics, and global medical affairs at J&J, said the results of the two trials support the combination therapy’s use.
“The data from CEPHEUS add to the body of evidence for daratumumab [subcutaneous] in newly diagnosed multiple myeloma and, together with the results of the PERSEUS study, demonstrate the potential benefit of this quadruplet regimen for newly diagnosed patients, regardless of transplant eligibility,” Tendler said.
About the Author
