Janssen seeks expanded approval for DARZALEX in treating AL amyloidosis

Janssen Pharmaceutical Companies of Johnson & Johnson has recently submitted a Type II variation application to the European Medicines Agency (EMA), aiming to extend the approval of its subcutaneous (SC) formulation of DARZALEX (daratumumab) for the treatment of light chain (AL) amyloidosis. This move reflects the growing recognition of AL amyloidosis as a serious and potentially fatal disease, with few treatment options available for patients to date.

What is AL amyloidosis and why is treatment important?

AL amyloidosis is a rare and life-threatening condition that occurs when amyloid, an insoluble protein, accumulates in various tissues and organs. This build-up disrupts the normal functioning of critical organs such as the heart, kidneys, and liver. The effects can be devastating, leading to severe organ dysfunction and failure. Given its rarity and complexity, AL amyloidosis often goes undiagnosed or misdiagnosed, making early intervention critical.

Currently, no therapeutics have been approved by regulatory bodies such as the EMA, the US Food and Drug Administration (FDA), or other international agencies to specifically treat AL amyloidosis. This gap in treatment options makes the approval of new therapies a critical step in improving patient outcomes.

The role of DARZALEX in treating AL amyloidosis

DARZALEX, an anti-CD38 monoclonal antibody, has already established itself as an essential treatment in multiple myeloma, a related plasma cell disorder. Janssen’s application for the expanded approval of DARZALEX in AL amyloidosis is based on the promising findings from the Phase 3 ANDROMEDA study, which investigated the efficacy of the SC formulation of daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd). This regimen was compared with the standard treatment of bortezomib, cyclophosphamide, and dexamethasone (VCd) alone.

Results from the ANDROMEDA study revealed significant improvements in patient outcomes, particularly in the haematologic complete response (CR) rate. Patients receiving the combination therapy with DARZALEX had a considerably higher CR rate compared to those treated with VCd alone. This suggests that daratumumab may play a pivotal role in improving both survival rates and quality of life for patients suffering from AL amyloidosis, a disease that typically has a poor prognosis.

Expert insights on the potential of DARZALEX in AL amyloidosis treatment

Craig Tendler, Vice President of Late Development and Global Medical Affairs at Janssen Research & Development, highlighted the significance of these findings, stating, “Daratumumab is an important foundational therapy in the treatment of multiple myeloma and now, on the basis of the ANDROMEDA study results, has shown that it can improve outcomes in a related plasma cell disorder, AL amyloidosis.”

Tendler emphasized the potential of DARZALEX in transforming the outlook for AL amyloidosis patients. “We are excited about the potential for daratumumab, as part of a regimen for newly diagnosed patients with AL amyloidosis, to alter the poor prognosis of their disease and reduce organ damage, which is an unfortunate life-threatening complication of this serious disease,” he said.

Regulatory milestones and future outlook

The submission to the EMA is the latest in a series of regulatory efforts aimed at gaining approval for the SC formulation of daratumumab. In September 2020, Janssen also submitted a supplemental biologics license application (sBLA) to the US FDA, seeking approval for the treatment of AL amyloidosis. The outcome of these submissions could mark a significant milestone in the treatment of AL amyloidosis, offering new hope for patients who currently have few options available to manage this debilitating disease.

With no current therapeutic alternatives approved by the EMA or FDA, the successful approval of DARZALEX in AL amyloidosis could offer a breakthrough in treating a disease that has long lacked effective treatment options. This development not only strengthens DARZALEX’s position in the field of plasma cell disorders but also reinforces Janssen’s commitment to advancing medical treatments that address critical unmet needs in rare diseases.