Submission inclusive of data from Phase 3 COLUMBA study presented at ASCO
RARITAN, NJ, USA I July 12, 2019 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of a new subcutaneous (SC) formulation of DARZALEX® (daratumumab), an intravenous (IV) treatment approved for certain patients with multiple myeloma.
The submission is supported by data from the Phase 3 COLUMBA (MMY3012) study first presented at the American Society of Clinical Oncology (ASCO) Annual Meeting that included a non-inferiority comparison to DARZALEX IV administration for co-primary endpoints of overall response rate and maximum Ctrough concentration. Data from the Phase 2 PLEIADES (MMY2040) study are also included in the BLA. The subcutaneous formulation of DARZALEX is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) [Halozyme’s ENHANZE® drug delivery technology].
“This submission represents our commitment to develop innovative treatment options for people living with multiple myeloma,” said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. “The DARZALEX subcutaneous formulation showed non-inferiority to the existing IV formulation, both as a monotherapy and in combination with common background therapies, while administered with a considerably shorter infusion time. We look forward to working closely with the FDA in their review of the data supporting this regulatory application.”
Today’s submission follows two recent milestones for the DARZALEX intravenous formulation, including an approval of DARZALEX in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed, transplant ineligible patients with multiple myeloma supported by the Phase 3 MAIA study, and Priority Review designation following submission of a supplemental BLA based on the Phase 3 CASSIOPEIA study, which is seeking approval of DARZALEX in combination with bortezomib, thalidomide and dexamethasone for newly diagnosed patients with multiple myeloma who are transplant eligible.
About the COLUMBA Study (MMY3012)1
The randomized, open-label, multicenter Phase 3 COLUMBA study included 522 patients with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease was refractory to both a PI and an IMiD (median age of 67). In the arm that received the SC formulation of DARZALEX (n=263), patients received a fixed dose of DARZALEX 1,800 milligrams (mg), co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) 2,000 Units per milliliter (U/mL), subcutaneously weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and thereafter. In the DARZALEX IV arm (n=259), patients received DARZALEX for IV infusion 16 milligrams per kilogram (mg/kg) weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and thereafter. Each cycle was 28 days. In the arm that received the SC formulation, DARZALEX was given as a fixed volume over 3 – 5 minutes. In the arm that received the IV administration, the median durations of the first, second and subsequent DARZALEX IV infusions were 7.0, 4.3 and 3.4 hours, respectively. Patients in both treatment arms continued until disease progression or unacceptable toxicity.
About the PLEIADES Study (MMY2040)2
The non-randomized, open-label, parallel assignment Phase 2 PLEIADES study included 240 adults either newly diagnosed or with relapsed or refractory multiple myeloma. Patients with newly diagnosed multiple myeloma were treated with 1,800 mg of the SC formulation in combination with either bortezomib, lenalidomide and dexamethasone (D-VRd) or bortezomib, melphalan, and prednisone (D-VMP). Patients with relapsed or refractory disease were treated with 1,800 mg of the SC formulation plus lenalidomide and dexamethasone (D-Rd). The primary endpoint for the D-VMP and D-Rd cohorts was overall response rate. The primary endpoint for the D-VRd cohort was very good partial response or better rate. An additional cohort of patients with relapsed and refractory multiple myeloma treated with daratumumab plus carfilzomib and dexamethasone was subsequently added to the study.
About DARZALEX® (daratumumab)
DARZALEX® (daratumumab), the first CD38-directed antibody approved anywhere in the world, is the only CD38-directed antibody approved to treat multiple myeloma.3 CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.4 DARZALEX binds to CD38 and inhibits tumor cell growth causing myeloma cell death.3 DARZALEX may also have an effect on normal cells.3 DARZALEX is being evaluated in a comprehensive clinical development program across a range of treatment settings in multiple myeloma, such as in frontline and relapsed settings.5,6,7,8,9,10,11,12 Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant hematologic diseases in which CD38 is expressed, such as smoldering myeloma.13,14
In the United States, DARZALEX received initial FDA approval in November 2015 as a monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.15 DARZALEX received additional approvals in November 2016 in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.16 In June 2017, DARZALEX received approval in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a PI.17 In May 2018, DARZALEX received approval in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT), making it the first monoclonal antibody approved for newly diagnosed patients with this disease.18 Most recently, in June 2019, DARZALEX was approved in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for ASCT.19 More than 80,000 patients have been treated with DARZALEX worldwide.
In August 2012, Janssen Biotech, Inc. entered into a global license and development agreement with Genmab A/S, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX.20 For the full U.S. Prescribing Information, please visit www.DARZALEX.com.
About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.21,22 When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow.22,23 In 2019, it is estimated that more than 32,000 people will be diagnosed, and nearly 13,000 will die from the disease in the United States.23 While some patients with multiple myeloma have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood counts, tiredness, high calcium levels, kidney problems or infections.24
About the Janssen Pharmaceutical Companies of Johnson & Johnson
At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are members of the Janssen Pharmaceutical Companies of Johnson & Johnson.
1 Mateos M-V et al. Efficacy and Safety of the Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Daratumumab (DARA) Administration in Patients (pts) With Relapsed or Refractory Multiple Myeloma (RRMM): COLUMBA. 2019 American Society of Clinical Oncology Annual Meeting. June 2019.
2 Janssen Research & Development, LLC. A Study to Evaluate Subcutaneous Daratumumab in Combination With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.
3 DARZALEX Prescribing Information, June 27, 2019.
4 Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFNγ Cytokines and Proliferation. Mediators Inflamm. 2013;564687.
5 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 July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02076009.
6 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 July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifier: NCT02136134.
7 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 July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006&rank=2 NLM Identifier: NCT02541383.
8 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 July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479.
9 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 July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172.
10 Janssen Research & Development, LLC. A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812.
11 European Myeloma Network. Comparison of Pomalidomide and Dexamethasone With or Without Daratumumab in Subjects With Relapsed or Refractory Multiple Myeloma Previously Treated With Lenalidomide and a Proteasome Inhibitor Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone. (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited July 5, 2019] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736
12 Amgen. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited July 5, 2019] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT03158688.
13 Janssen Research & Development, LLC. A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants With Smoldering Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106?term=smm2001&rank=1 Identifier: NCT02316106.
14 Janssen Research & Development, LLC. An Efficacy and Safety Proof of Concept Study of Daratumumab in Relapsed/Refractory Mantle Cell Lymphoma, Diffuse Large B-Cell Lymphoma, and Follicular Lymphoma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489
15 Janssen Biotech, Inc. “DARZALEX® (daratumumab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma.” Issued November 16, 2015.
16 Janssen Biotech, Inc. “DARZALEX® (daratumumab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma Who Have Received At Least One Prior Therapy.” Issued November 21, 2016.
17 Janssen Biotech, Inc. “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.” Issued June 16, 2017.
18 Janssen Pharmaceutical Companies of Johnson & Johnson. “Janssen Announces DARZALEX® (daratumumab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible.” Issued May 7, 2018.
19 Janssen Pharmaceutical Companies of Johnson & Johnson. “Janssen Announces U.S. FDA Approval of DARZALEX® (daratumumab) in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible.” Issued June 27, 2019.
20 Janssen Biotech, Inc. “Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab.” Issued August 30, 2012.
21 Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
22 American Cancer Society. “What Is Multiple Myeloma?” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed July 2019.
23 American Cancer Society. “Key Statistics for Multiple Myeloma.” Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed July 2019.
24 American Cancer Society. “Diagnosing Multiple Myeloma From Test Results.” Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed July 2019.
SOURCE: Janssen
