DARZALEX®▼ (daratumumab) Subcutaneous (SC) Formulation Becomes the First Approved Treatment for Newly Diagnosed Systemic Light Chain Amyloidosis in Europe and Gains an Additional Approval in Pre-Treated Multiple Myeloma

DARZALEX®▼ (daratumumab) Subcutaneous (SC) Formulation Becomes the First Approved Treatment for Newly Diagnosed Systemic Light Chain Amyloidosis in Europe and Gains an Additional Approval in Pre-Treated Multiple Myeloma

Approval of daratumumab SC-based regimen in Light Chain (AL) amyloidosis is supported by the Phase 3 ANDROMEDA study, which demonstrated significantly higher haematologic complete response rate vs. commonly used standard-of-care regimen

Daratumumab SC is also now the first subcutaneous anti-CD38 monoclonal antibody approved in combination with pomalidomide and dexamethasone in pre-treated multiple myeloma

Beerse, Belgium, 22 June, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the European Commission (EC) has granted marketing authorisation for the expanded use of DARZALEX®▼ (daratumumab) subcutaneous (SC) formulation in two new indications. The first authorisation of these new indications is for the use of daratumumab SC in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adults with newly diagnosed systemic light chain (AL) amyloidosis. This approval makes this daratumumab-based regimen the first approved therapy for AL amyloidosis in Europe.

The second authorisation is for the use of daratumumab SC in combination with pomalidomide and dexamethasone (D-Pd) for the treatment of adults with multiple myeloma (MM) who have received one prior therapy containing a proteasome inhibitor and lenalidomide and were lenalidomide refractory, or who have received at least two prior therapies that included lenalidomide and a proteasome inhibitor, and have demonstrated disease progression on or after the last therapy.

Both AL amyloidosis and MM are complex, incurable blood disorders. AL amyloidosis is a rare and potentially life-threatening disorder caused by a build-up of amyloid, an insoluble protein, in tissues and organs.1,2 This eventually causes organ deterioration, most commonly in the heart, kidneys and liver.3

Multiple myeloma remains an incurable cancer of the plasma cells found in the bone marrow.4 While there have been several developments in treatments over the years, the complex nature of the disease means that patients can often become resistant to therapy.5 Outcomes worsen with each relapse and the need for effective treatment options becomes crucial.5,6

“Today’s approvals mark significant progress for patients living with these blood disorders, especially for AL amyloidosis where patients have long faced an urgent need for approved treatment options,” said Edmond Chan, Senior Director, EMEA Therapeutic Area Lead Hematology, Janssen-Cilag Limited. “The outlook for untreated patients has been poor with an average survival of 12-18 months, and only six months for those with severely impaired heart function. Our goal is to change these statistics and offer new hope to patients facing an AL amyloidosis diagnosis.”

The EC approval for the AL amyloidosis indication is based on positive results from the Phase 3 ANDROMEDA study, recently presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting and at the 26th European Haematology Association (EHA) Congress.7,8 The study evaluated D-VCd compared with VCd alone, a common treatment regimen used in adult patients with newly diagnosed AL amyloidosis. Patients receiving treatment with daratumumab experienced a significantly higher haematologic complete response rate (haemCR) compared to patients receiving VCd alone (59 percent vs. 19 percent; p<0.0001).7 Furthermore, at 20.3 months median follow up, more patients achieved a very good partial response or better (≥VGPR) with D-VCd than VCd (79 percent vs 50 percent).7 Overall, D-VCd had a safety profile consistent with that previously observed for each of the agents alone.7

“AL amyloidosis is a rare haematological disorder and can be incredibly challenging to diagnose as symptoms are often subtle and can mimic other conditions. This challenge is further compounded by limited treatment options,” said Efstathios Kastritis*, M.D., Professor of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece and ANDROMEDA study investigator. “The approval of daratumumab is therefore welcome news for patients and the medical community as the addition of daratumumab to VCd, which has until now been the standard-of-care regimen for treating AL amyloidosis, has been shown to induce deep responses in patients, not only inducing remission at a significantly greater rate than VCd alone, but also significantly improving cardiac and renal responses and delaying major organ deterioration.”

“At Janssen, our goal is to deliver transformative innovations to patients with complex blood disorders,” said Jessica Vermeulen, M.D., Ph.D., Vice President Clinical R&D, Late Stage Development, Hematology, Janssen Biologics B.V. “We are focused on the continued research and development of daratumumab for patients who are in need of additional treatment options, and we look forward to realising the impact daratumumab will have in these new indications.”

The EC approval for daratumumab SC in combination with Pd in the treatment of pre-treated MM is based on positive findings from the Phase 3 APOLLO study recently published in The Lancet Oncology. An updated analysis of the study, featuring health-related quality of life data, was also presented at the American Society of Clinical Oncology (ASCO) Annual Meeting and the 26th European Hematology Association (EHA) Congress.

The APOLLO study met its primary endpoint of improved progression-free survival (PFS), demonstrating that D-Pd significantly reduced the risk of progression or death by 37 percent, compared to Pd alone (hazard ratio, 0.63; 95 percent confidence interval [CI], 0.47-0.85; P=0.0018).9 The median PFS for the D-Pd arm vs. Pd arm was 12.4 vs. 6.9 months, respectively.9 Study findings additionally showed the rate of overall response to be significantly higher in D-Pd compared to Pd alone (69 percent vs 46 percent), as well as rates of complete response or better (25 percent vs 4 percent) and very good partial response or better (51 percent vs 20 percent).9 Additionally, more patients treated with D-Pd showed a negative status for minimal residual disease than patients receiving Pd alone (9 percent vs 2 percent).9 Furthermore, D-Pd demonstrated a consistent safety profile with the known profiles of daratumumab SC or Pd alone.9