J&J's Darzalex succeeds in Phase 3 early-stage multiple myeloma trial

Johnson & Johnson's CD38 inhibitor, Darzalex, has demonstrated a significant benefit in delaying or preventing disease progression in patients with high-risk smoldering multiple myeloma, which is a precursor to active multiple myeloma. The Phase 3 Aquila trial's primary endpoint, progression-free survival, was notably improved for those receiving Darzalex, achieving a p-value of 0.0001. Estimated 60-month progression-free survival rates were 63.1% for those on the drug compared to 40.8% for those under active monitoring. Additionally, the overall response rate was markedly higher at 63.4% for the Darzalex group versus a mere 2% for the active monitoring group, also earning a p-value of 0.0001.

A secondary endpoint of overall survival showed a positive trend favoring Darzalex, with 93% survival in the Darzalex group compared to 86.9% in the active monitoring group. In the trial, there were 41 deaths recorded: 15 in the treatment group and 26 in the active monitoring group.

However, Grade 3 or 4 treatment-emergent adverse events were observed in 40.4% of patients receiving Darzalex, compared to 30.1% in the active monitoring group. Furthermore, 5.7% of patients on Darzalex discontinued treatment due to adverse effects.

The study authors emphasized the strong support for early intervention with Darzalex monotherapy over active monitoring, which is currently the standard of care for patients with high-risk smoldering multiple myeloma.

In response to a query about the regulatory plans for Darzalex in treating high-risk smoldering multiple myeloma, a Johnson & Johnson representative indicated that the company is actively collaborating with regulatory authorities worldwide on the clinical development program for Darzalex and exploring potential future indications.

Darzalex is already approved for seven different multiple myeloma indications and achieved sales of $9.74 billion in 2023, including over $3 billion in the third quarter of 2024. Additionally, in September, Johnson & Johnson shared positive data from several late-stage studies of Darzalex in patients with newly-diagnosed multiple myeloma who had undergone an autologous stem cell transplant. The company has also filed a supplemental Biologics License Application (BLA) for Darzalex in combination with chemotherapy for treating newly-diagnosed multiple myeloma patients who have not had a stem cell transplant.