Following the FDA's green light for a combo regimen of Sanofi’s Sarclisa in patients with newly diagnosed multiple myeloma last week, J&J has wasted little time hitting back with new data on its own cancer quartet leveraging the company’s subcutaneous oncology stalwart Darzalex Faspro.
In a Friday data drop from the phase 3 CEPHEUS study, J&J revealed that Darzalex Faspro combined with bortezomib, lenalidomide and dexamethasone (VRd) in first-line, transplant ineligible multiple myeloma patients yielded a significant improvement over VRd in minimal residual disease (MRD) negativity rates, progression-free survival (PFS) and the rates of complete responses (CR) or better.
MRD negativity references a deep tumor clearance threshold that the FDA appears poised to allow as a surrogate endpoint for accelerated approvals for new myeloma therapies. An FDA advisory committee in April unanimously backed the establishment of the surrogate endpoint following two meta-analyses of past clinical trials that pointed to MRD negativity’s potential to predict longer-term outcomes such as PFS.
J&J presented the new CEPHEUS data at the 2024 annual meeting of the International Myeloma Society this week.
Digging deeper into the data, patients on Darzalex-VRd achieved an overall MRD negativity rate of 60.9% at around 59 months versus 39.4% in the cohort that received the VRd regimen alone. This result allowed the trial to hit its primary endpoint, J&J said in a release.
The proportion of patients on Darzalex-VRd who achieved sustained MRD negativity for at least 12 months reached 48.7%, nearly double the 26.3% rate from the trial’s VRd arm.
CEPHEUS also showed that Darzalex-VRd significantly reduced the risk of progression or death by 43% when pitted against VRd alone. Median PFS was not reached for the Darzalex combo, while the VRd group's result was 52.6 months.
Lastly, the Darzalex quadruplet regimen triggered a complete response or better in 81.2% of patients compared to 61.6% for the VRd regimen. The company noted that overall survival data in the study are not yet mature.
J&J did not speak to regulatory plans for the Darzalex-based cancer quartet, though the company’s global oncology and innovative medicine chief, Robin Carson, M.D., noted in a statement that the company is excited about “continuing to advance this potential new quadruplet therapy.”
The timing of the data drop is key given that Sanofi just last week broke into first-line multiple myeloma with its own VRd-featuring regimen leveraging its CD38 antibody Sarclisa. The FDA’s approval cleared the Sanofi cancer quadruplet in newly diagnosed patients who are not eligible for stem cell transplants.
Prior to that nod, J&J’s Darzalex had been the lone CD38 antibody approved for newly diagnosed myeloma since 2018—that transplant-ineligible greenlight covers a regimen of Darzalex plus bortezomib, melphalan and prednisone, rather than the VRd combo the company is testing now.
Still, Darzalex remains king in the multiple myeloma arena, with multiple regimens approved for both transplant-eligible and -ineligible patients. In 2023, sales of the franchise leapt 22% to $9.7 billion, while Sarclisa reeled in $381 million (a 30% year-over-year increase) over the same 12-month stretch.
Meanwhile, CEPHEUS wasn’t the only Darzalex study to yield results this week.
In a separate release from the late-stage AURIGA study, J&J announced that Darzalex Faspro plus lenalidomide maintenance therapy significantly boosted MRD negative conversion rates at 12 months versus lenalidomide alone. That study specifically looked at J&J’s drug in newly diagnosed myeloma patients who received an autologous stem cell transplant.
"These results, along with the data being presented from the Phase 3 CEPHEUS study, further underscore the promising potential of Darzalex Faspro for newly diagnosed patients, regardless of their transplant status,” Imran Khan, J&J's VP of medical affairs for hematology and innovative medicine, said in a statement.