Janssen Submits Applications in the EU and U.S. Seeking Approval of DARZALEX®▼ (daratumumab) Subcutaneous Formulation in Combination With Pomalidomide and Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma

Janssen Submits Applications in the EU and U.S. Seeking Approval of DARZALEX^®▼ (daratumumab) Subcutaneous Formulation in Combination With Pomalidomide and Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma   Applications supported by positive results from the Phase 3 APOLLO study, which demonstrated improved significant progression-free survival in patients receiving the subcutaneous formulation of daratumumab[i]  

BEERSE, BELGIUM, 12 November, 2020 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of regulatory applications to the European Medicines Agency (EMA) and United States (U.S.) Food and Drug Administration (FDA) seeking approval of the subcutaneous formulation of daratumumab, known as DARZALEX^®▼ subcutaneous (SC) formulation within the European Union (EU) and DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) in the U.S. These applications seek approval of the combination of daratumumab SC with pomalidomide and dexamethasone (D-Pd) for the treatment of patients with relapsed or refractory multiple myeloma. As a fixed-dose formulation, daratumumab SC can be administered over approximately three to five minutes, significantly less time than the intravenous formulation (IV) of daratumumab, which is given over several hours.

The Type II variation application to the EMA and the supplemental Biologics License Application (sBLA) to the U.S. FDA are supported by positive findings from the Phase 3 APOLLO study (MMY3013). The APOLLO study is the first and only study showing the benefit of subcutaneous anti-CD-38 monoclonal antibody (mAb) in combination with pomalidomide and dexamethasone. The study met its primary endpoint with improved progression-free survival (PFS) in patients receiving D-Pd compared with Pd alone in patients with relapsed or refractory multiple myeloma.[ii] Overall, the safety profile of D-Pd demonstrated a consistent safety profile with that of each therapy separately.² The most common adverse reactions seen with D-Pd were neutropenia, anemia and leukopenia.²

Full results from the Phase 3 APOLLO study, a collaboration between Janssen Research & Development, LLC and the European Myeloma Network (EMN), will be presented in an oral session at the upcoming American Society of Hematology (ASH) Annual Meeting on Sunday, December 6, 2020 at 9:00 a.m. Central European Time (3:00 p.m. Eastern Time) (Abstract #412).

The D-Pd regimen received approval from the U.S. FDA for the intravenous (IV) formulation of daratumumab in 2017 for patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.[iii] This regimen for the IV formulation has not previously been submitted for approval to the EMA.

“The IV formulation of daratumumab in combination with pomalidomide and dexamethasone is an important option for patients with multiple myeloma. We are excited to pursue daratumumab subcutaneous formulation for this indication as we look to improve patient outcomes and reduce administration time from hours to minutes compared to the IV formulation,” said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. “Today’s regulatory milestones represent our continued commitment to advance innovative treatments for people living with multiple myeloma.”

Daratumumab was first approved as a monotherapy for the treatment of multiple myeloma in 2015 in the U.S. and in 2016 in the EU, making it the first anti-CD38 monoclonal antibody indicated anywhere in the world for multiple myeloma.[iv]^,[v] In 2020, the subcutaneous formulation of daratumumab was approved by the U.S. FDA and European Commission (EC) as the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma.[vi]^,[vii] Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE^® drug delivery technology. As of 2020, daratumumab has been approved by global regulatory authorities across six combination regimens and as a monotherapy for the treatment of newly diagnosed patients, across relapsed and refractory multiple myeloma.^{4,[viii],[ix],[x],[xi],[xii]}

“Despite strong progress in multiple myeloma over the last decade, it remains a disease with significant unmet need,” said Dr Catherine Taylor, VP, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd. Middle East. “We are pleased to pursue this important daratumumab-based combination regimen, which is the first study showing a benefit of subcutaneous anti-CD38 in combination in patients with previously treated multiple myeloma.”

[i] Comparison of Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide and a Proteasome InhibitorDaratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). Available at: https://clinicaltrials.gov/ct2/show/record/NCT03180736 Last accessed: November 2020.

[ii] Chari A, et al. “Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma.” Blood. 2017;130(8): 974-981.

[iii] Johnson & Johnson. DARZALEX® (daratumumab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies. Available at: https://www.jnj.com/media-center/press-releases/darzalex-daratumumab-approved-by-the-us-fda-in-combination-with-pomalidomide-and-dexamethasone-for-patients-with-multiple-myeloma-who-have-received-at-least-two-prior-therapies Last accessed: November 2020.

[iv] Johnson& Johnson. DARZALEX® (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma. Available at: https://www.jnj.com/media-center/press-releases/darzalex-daratumumab-approved-by-us-fda-first-human-anti-cd38-monoclonal-antibody-available-for-the-treatment-of-multiple-myeloma Last accessed: November 2020.

[v] Janssen EMEA. Janssen’s Single-Agent DARZALEX® (Daratumumab) Approved by European Commission for Treatment of Multiple Myeloma (MM). Available at:  www.janssen.com/emea/sites/www_janssen_com_emea/files/janssen_darzalex_ec_approval_press_release_2016_05_23_final.pdf. Last accessed: November 2020.

[vi] U.S. Food and Drug Administration Center for Drug Evaluation and Research. FDA Approves Daratumumab and Hyaluronidase-Fihj for Multiple Myeloma. Available at: www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-daratumumab-and-hyaluronidase-fihj-multiple-myeloma Last accessed: November 2020.

[vii] Janssen EMEA. European Commission Grants Marketing Authorisation for DARZALEX®▼(Daratumumab) Subcutaneous Formulation for All Currently Approved Daratumumab Intravenous Formulation Indications. Available at: www.businesswire.com/news/home/20200604005487/en/European-Commission-Grants-Marketing-Authorisation-for-DARZALEX%C2%AE%E2%96%BC-daratumumab-Subcutaneous-Formulation-for-all-Currently-Approved-Daratumumab-Intravenous-Formulation-Indications. Last accessed: November 2020.

[viii] Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02136134. Last accessed: November 2020.

[ix] Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifier: NCT02076009. Last accessed: November 2020.

[x] Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006 Identifier: NCT02541383. Last accessed: November 2020.

[xi] Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479. Last accessed: November 2020.

[xii] Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172. Last accessed: November 2020.