Janssen's CD38-Based Combination Therapy Achieves 53% Hematologic Complete Response Rate in Phase 3 Trial for AL Amyloidosis

Today, Genmab announced that daratumumab, a CD38 antibody co-developed with Janssen, met the primary endpoint in the Phase 3 ANDROMEDA clinical trial evaluating its efficacy in combination with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for the treatment of patients with newly diagnosed immunoglobulin light chain (AL) amyloidosis.

AL Amyloidosis is a rare systemic disease. In patients with this condition, certain plasma cells overproduce immunoglobulin light chains, leading to their misfolding and aggregation into fibrils that deposit within and around tissues, causing widespread and progressive organ damage. The median survival time for diagnosed patients is less than 18 months, with heart failure being the most common cause of death. Although there are currently some treatment options such as chemotherapy and autologous stem cell transplantation, no approved therapies exist for addressing the organ damage caused by AL amyloidosis. Therefore, new treatments are urgently needed for this fatal disease.

Daratumumab can specifically recognize CD38, which is highly expressed on malignant plasma cells in multiple myeloma, with high affinity, thereby inducing tumor cell death through various immune-mediated mechanisms. Since its launch in 2015, this drug has received multiple FDA approvals to expand its indications for treating patients with multiple myeloma. Last June, the FDA approved its use in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma patients who are not eligible for autologous stem cell transplantation. Although AL amyloidosis differs significantly from multiple myeloma in pathogenesis, the plasma cells that overproduce immunoglobulin light chains also express CD38, making them susceptible to targeted clearance by daratumumab.

A total of 388 patients with AL amyloidosis participated in the ANDROMEDA study and were randomly assigned to receive either daratumumab in combination with CyBorD or CyBorD alone. Trial data demonstrated that the daratumumab-based combination therapy met the primary endpoint of hematologic complete response rate. The hematologic complete response rate was 53.3% among patients receiving the combination therapy, compared with 18.1% among those receiving CyBorD alone.

“We are very pleased with the positive top-line results from our Phase 3 ANDROMEDA study in patients with AL amyloidosis,” said Dr. Jan van de Winkel, Chief Executive Officer of Genmab. “Currently, there are no approved therapies for AL amyloidosis. We believe these data support the potential of daratumumab in treating this progressive disease.”

References:

[1] Genmab Announces Positive Topline Results in Phase III ANDROMEDA Study of Daratumumab in Light-chain (AL) Amyloidosis. Retrieved 2020-05-29, from http://www.globenewswire.com/news-release/2020/05/28/2040461/0/en/Genmab-Announces-Positive-Topline-Results-in-Phase-III-ANDROMEDA-Study-of-Daratumumab-in-Light-chain-AL-Amyloidosis.html

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