European Commission Approves Darzalex®▼ (daratumumab) in Combination with Bortezomib, Thalidomide and Dexamethasone (VTd) for Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Eligible

• Daratumumab-VTd is the first regimen approved in over six years for newly diagnosed patients who are eligible for a stem cell transplant[1]
• Approval is based on data from the Phase 3 CASSIOPEIA trial, which demonstrated that the addition of daratumumab resulted in deeper response rates and improved progression-free survival (PFS) compared to VTd alone[2]
• Daratumumab has been used to treat more than 100,000 patients worldwide[3]
• This is the sixth approval for daratumumab and the third in the frontline setting[4]

BEERSE, BELGIUM, 20 January 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the European Commission (EC) has granted marketing authorisation for Darzalex^® (daratumumab) in combination with bortezomib, thalidomide and dexamethasone (VTd) for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT). This approval is based on results from Part one of the Phase 3 CASSIOPEIA (MMY3006) study, published in The Lancet^[5] in June 2019 and presented at the 2019 American Society of Clinical Oncology (ASCO) Meeting.

“The effectiveness of first-line treatment is critical to maximise time until relapse. So, we asked ourselves, can we improve the standard of care that is bortezomib, thalidomide and dexamethasone (VTd) to provide patients with valuable extra time?” said Philippe Moreau, M.D., principal investigator and Head of the Haematology Department at the University Hospital of Nantes, France. “The CASSIOPEIA study answered that question definitively, demonstrating that the addition of daratumumab in combination with VTd can lead to very deep remissions and also prolong PFS. I’m pleased to see the European Commission have recognised this as well.”

“Today’s approval marks the first opportunity for newly diagnosed, transplant eligible patients to be treated with a monoclonal antibody, and the first new treatment for this patient population in over six years,” said Dr Patrick Laroche, Haematology Therapy Area Lead, Europe, Middle East and Africa (EMEA), Janssen-Cilag. “We are thrilled that newly diagnosed patients with multiple myeloma and their doctors will have a long-awaited additional frontline therapy.”

The Phase 3 CASSIOPEIA trial is a two-part study. Results from this first part of the trial showed that after consolidation, the stringent complete response (sCR) rate was significantly higher in the daratumumab-VTd arm (29 percent) compared to VTd alone (20 percent) (Odds Ratio [OR] = 1.60; 95 percent confidence interval [CI], 1.21-2.12; P<0.0010).² At a median follow-up of 18.8 months, PFS was significantly improved in the daratumumab-VTd group compared to VTd alone (Hazard Ratio [HR] = 0.47; 95 percent CI, 0.33-0.67; P<0.0001), and the median PFS was not reached in either arm.² The addition of daratumumab to VTd resulted in an 18-month PFS rate of 93 percent compared to 85 percent for VTd alone.²

The most common (≥10%) Grade 3/4 treatment-emergent adverse events (TEAEs) for daratumumab-VTd and VTd, respectively, were neutropenia (28 percent vs. 15 percent), lymphopenia (17 percent vs. 10 percent), stomatitis (13 percent vs. 16 percent) and thrombocytopenia (11 percent vs. 7 percent).² In the daratumumab-VTd combination arm, infusion-related reactions occurred in 35 percent of patients.²

“This approval represents our commitment to investigate daratumumab in earlier disease stages of multiple myeloma and to develop more effective frontline treatment options for newly diagnosed patients who are eligible for transplantation,” adds Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC.

[1] Johnson & Johnson. European Commission Approves VELCADE® As A Frontline Induction Therapy Before Stem Cell Transplantation. Press release August 8, 2013. Available at: https://www.jnj.com/media-center/press-releases/european-commission-approves-velcade-as-a-frontline-induction-therapy-before-stem-cell-transplantation Last accessed January 2020.

[2] Moreau P, Attal M, Hulin C, et al. Phase 3 randomized study of daratumumab (DARA) + bortezomib/thalidomide/dexamethasone (D-VTd) vs VTd in transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM): CASSIOPEIA Part 1 results. Presented at Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, USA, 31 May – 4 June 2019.

[3] Janssen. Data on file: RF-82203. Daratumumab: New patient starts launch to date. December 2019

[4] European Medicines Agency. DARZALEX summary of product characteristics, November 2019. Available at: https://ec.europa.eu/health/documents/community-register/2019/20191119146548/anx_146548_en.pdf Last accessed January 2020.

[5] Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. The Lancet. Volume 394, Issue 10192, P29-38, July 06, 2019.