Janssen Submits Application Seeking U.S. FDA Approval of DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) for the Treatment of Patients with Light Chain (AL) Amyloidosis

Application is based on positive results from the Phase 3 ANDROMEDA study evaluating the efficacy and safety of combination therapy with DARZALEX FASPRO™

RARITAN, NJ, USA I September 10, 2020 I The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) seeking approval of DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, for the treatment of patients with light chain (AL) amyloidosis, a rare and potentially fatal disease for which there are no currently approved therapies.1,2 The sBLA is supported by positive results from the Phase 3 ANDROMEDA study, which were presented as a late-breaking abstract at the 25th European Hematology Association Annual Congress in June. ANDROMEDA evaluated subcutaneous daratumumab in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) compared to VCd alone and met its primary endpoint of overall hematologic complete response rate.  

"We are excited about the potential of helping patients with AL amyloidosis who currently have no FDA-approved therapies for the treatment of their disease," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "The results from the Phase 3 ANDROMEDA study also provide preliminary evidence of DARZALEX FASPRO's potential to modify the organ damage that is a hallmark of this serious disease with high unmet needs and we look forward to collaborating with the agency in the review of the application."

The sBLA is being reviewed under the FDA Real-Time Oncology Review (RTOR) program, which allows data for certain applications to be reviewed before the applicant formally submits the complete application. The RTOR program aims to explore a more efficient review process to help ensure treatments are available as soon as possible for patients. Selection into the RTOR program does not guarantee or influence approvability of the supplemental application.

The submission is also being reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence, which provides a framework for concurrent submission and review of oncology medicine applications among international regulatory agencies.3

AL amyloidosis is a life-threatening disorder that occurs when plasma cells in the bone marrow produce abnormal light chains, that form amyloid deposits, which build up in vital organs and eventually cause organ deterioration.1,2 The disease can affect different organs in different people, but the most frequently affected organs are the heart, kidneys, liver, spleen, GI tract and nervous system.4 Diagnosis of AL amyloidosis is often delayed because patients present with non-specific symptoms that mimic other conditions, resulting in a poor prognosis.5 There are currently no FDA-approved therapies to treat this devastating disease. While AL amyloidosis is the most common type of amyloidosis, it remains a rare disease with an estimated 30,000 to 45,000 people living with the disease in the U.S. and Europe.6 Each year, an estimated 4,500 people develop AL amyloidosis in the U.S. alone.6

About the ANDROMEDA Study7
ANDROMEDA (NCT03201965) is an ongoing Phase 3, randomized, open-label study investigating the safety and efficacy of daratumumab and hyaluronidase-fihj in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, for the treatment of patients with newly diagnosed light chain (AL) amyloidosis. The study includes 388 patients with newly diagnosed AL amyloidosis with measurable hematologic disease and one or more organs affected. The primary endpoint is overall complete hematologic response rate by intent-to-treat (ITT). Secondary endpoints include major organ deterioration progression-free survival, event-free survival, organ response rate, overall survival, and time to hematologic response, among others.

About DARZALEX FASPRO
Janssen is committed to exploring the potential of DARZALEX FASPRO™ (daratumumab and hyaluronidase-fihj) for patients with multiple myeloma (MM) across the spectrum of the disease.

In August 2012, Janssen entered into an exclusive global license and development agreement with Genmab A/S to develop, manufacture and commercialize DARZALEX®.8  In 2020, DARZALEX FASPRO™ (daratumumab and hyaluronidase human-fihj) was approved as the only subcutaneous CD38-directed antibody approved to treat patients with MM.9 DARZALEX FASPRO™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme's ENHANZE® drug delivery technology.

CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.4 Daratumumab binds to CD38 and inhibits tumor cell growth causing myeloma cell death.5 DARZALEX FASPRO™ may also have an effect on normal cells.10 Data across seven Phase 3 clinical trials, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.11,12,13,14,15,16,17,18 Additional studies are underway to assess the efficacy and safety of DARZALEX FASPRO™ in the treatment of other malignant and pre-malignant hematologic diseases in which CD38 is expressed, including smoldering myeloma and in AL amyloidosis.19,20

Please see full Prescribing Information at www.DARZALEX.com.

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.

1 National Organization for Rare Disorders. Amyloidosis. Accessed September 2020. https://rarediseases.org/rare-diseases/amyloidosis/.
2 Lousada I, Comenzo RL, Landau H, et al. Light chain amyloidosis: patient experience survey from the Amyloidosis Research Consortium. Advances in Therapy. 2015;32(10):920-928.
3 Project Orbis. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis. Accessed September 2020.
4 Mayo Clinic. Amyloidosis overview: symptoms and causes. Accessed September 2020. https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178.
5 Amyloidosis Support. Amyloidosis Awareness. Available at: https://www.amyloidosissupport.org/AmyloidAware_Booklet.pdf. Published October 2013. Accessed September 2020.
6 Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2(10):1046–1053. doi:10.1182/bloodadvances.2018016402. Accessed September 2020.
7 Kastritis, E. et al. Subcutaneous Daratumumab + Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) in Patients with Newly Diagnosed Light Chain (AL) Amyloidosis: Primary Results from the Phase 3 ANDROMEDA Study. Available at: https://library.ehaweb.org/eha/2020/eha25th/303396/efstathios.kastritis.subcutaneous.daratumumab.2B.cyclophosphamide.bortezomib.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Amedia%3D3%2Ace_id%3D1766%2Asearch%3Ddaratumumab%2Bamyloidosis. Accessed September 2020.
8 Janssen Biotech, Inc. "Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab." Issued August 30, 2012.
9 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.
10 2020 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.
11 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.
12 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.
13 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.
14 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.
15 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.
16 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 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812.
17 European Myeloma Network. Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736
18 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 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT03158688.
19 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 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT02316106.
20 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 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT02413489?term=lym2001&rank=1 Identifier: NCT02413489

SOURCE: Janssen

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