January 15, 2021 (HORSHAM, Pa.) – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the U.S. Food and Drug Administration (FDA) approval of Darzalex Faspro® (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis. Darzalex Faspro® is the first and only FDA-approved treatment for patients with this blood cell disorder that is associated with the production of an abnormal protein, which leads to the deterioration of vital organs, most notably the heart, kidneys and liver., This indication is approved under accelerated approval and is based on the hematologic complete response rate (hemCR) measure. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Darzalex Faspro® is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.
“Today’s milestone is an important step for patients diagnosed with this rare disease,” said Isabelle Lousada, Founder and CEO, Amyloidosis Research Consortium. “Sadly, most patients with AL amyloidosis are diagnosed more than one year after their initial symptoms present, at a time when they may already be experiencing organ deterioration or failure. I believe this approval will increase awareness of and education around this life-threatening disease and offer new hope for people with AL amyloidosis and their caregivers.”
The FDA approval is based on positive results from the Phase 3 ANDROMEDA study, which were recently presented at the American Society of Hematology (ASH) 2020 Annual Meeting. The study evaluated Darzalex Faspro® in combination with VCd, compared with VCd alone, a common treatment regimen used in adult patients with newly diagnosed AL amyloidosis. Patients receiving treatment with Darzalex Faspro® experienced a hemCR more than triple that of patients receiving VCd alone (42 percent for D-VCd and 13 percent for VCd; P<0.0001).1
“There is an urgent need for awareness and treatment options to help in the fight against this serious blood cell disorder,” said Raymond L. Comenzo, M.D., Director, John C. Davis Myeloma and Amyloid Program, Tufts Medical Center, and ANDROMEDA study investigator. “Achieving hematologic complete response is an important treatment goal, and today’s approval based on this clinical endpoint will provide doctors and the larger medical community with a new option to treat newly diagnosed patients.”
Approximately 4,500 people in the U.S. develop this rare disease each year. AL amyloidosis is a life-threatening blood cell disorder that occurs when blood plasma cells in the bone marrow produce amyloid deposits, which build up in vital organs and eventually cause organ deterioration.3 The disease can affect different organs in different people, but the most frequently affected organs are the heart, kidneys, liver, spleen, gastrointestinal tract and nervous system.2,3 About one-third of patients visit five or more doctors before receiving a diagnosis, and 72 percent are diagnosed more than one year after they first experience symptoms.3,4 Patients often have a poor prognosis due to the delay in diagnosis of AL amyloidosis, which frequently presents with non-specific symptoms that can mimic other, more common conditions. As many as 30 percent of patients with AL amyloidosis die within the first year after diagnosis.
“Darzalex Faspro, as the first and only FDA-approved treatment for newly diagnosed AL amyloidosis, marks a significant advance for a disease with high unmet medical need,” said Jessica Vermeulen, M.D., Ph.D., Global Medical Head/Clinical Leader, Hematology & Oncology, Janssen Research & Development, LLC. “Today’s approval underscores our commitment to deliver innovative therapies for patients with plasma cell diseases.”
The most common adverse reactions (≥20 percent) were upper respiratory tract infection, diarrhea, peripheral edema, constipation, fatigue, peripheral sensory neuropathy, nausea, insomnia, dyspnea and cough. Serious adverse reactions occurred in 43 percent of patients who received Darzalex Faspro® in combination with VCd. Serious adverse reactions that occurred in at least 5 percent of patients in the D‑VCd arm were pneumonia (9 percent), cardiac failure (8 percent) and sepsis (5 percent). Fatal adverse reactions occurred in 11 percent of patients. Fatal adverse reactions that occurred in more than one patient included cardiac arrest (4 percent), sudden death (3 percent), cardiac failure (3 percent) and sepsis (1 percent).1
Among patients who received Darzalex Faspro® in combination with VCd, 72 percent of patients had baseline cardiac involvement with Mayo Cardiac Stage I (3 percent), Stage II (46 percent) and Stage III (51 percent). Serious cardiac disorders occurred in 16 percent of patients (8 percent of patients with Mayo Cardiac Stage I and II and 28 percent of patients with Stage III). Serious cardiac disorders in more than 2 percent of patients included cardiac failure (8 percent), cardiac arrest (4 percent) and arrhythmia (4 percent). Fatal cardiac disorders occurred in 10 percent of patients (5 percent of patients with Mayo Cardiac Stage I and II and 19 percent of patients with Stage III) who received Darzalex Faspro® in combination with VCd. Fatal cardiac disorders that occurred in more than one patient in the D-VCd arm included cardiac arrest (4 percent), sudden death (3 percent) and cardiac failure (3 percent).1
The FDA reviewed and approved this indication 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 and timely 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 was also 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.
About the ANDROMEDA Study
ANDROMEDA1 (NCT03201965) is an ongoing Phase 3, randomized, open-label study investigating the safety and efficacy of Darzalex Faspro® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, for the treatment of adult 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). Patients received Darzalex Faspro® 1,800 mg/ 30,000 units administered subcutaneously once weekly from weeks 1 to 8, once every 2 weeks from weeks 9 to 24 and once every 4 weeks starting with week 25 until disease progression or unacceptable toxicity or a maximum of 2 years. Among patients who received D-VCd, 74 percent were exposed for 6 months or longer and 32 percent were exposed for greater than one year.
About Darzalex Faspro®
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. Darzalex Faspro® is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma and now AL amyloidosis. Darzalex Faspro® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
Darzalex Faspro® is indicated for the treatment of adult patients with multiple myeloma:
- in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
Access to Darzalex Faspro® (daratumumab hyaluronidase-fihj)
Janssen offers comprehensive access and support information, resources and services to assist U.S. patients in gaining access to Darzalex Faspro® through the Janssen CarePath Savings Program. Through the program, patients with commercial insurance plans will pay $5 per injection with a $20,000 maximum program benefit per calendar year. This program is not valid for patients using Medicare, Medicaid, or other government-funded programs to pay for their medications. Information on the enrollment process is available online at www.CarePathSavingsProgram.com/DARZALEX.
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 and www.twitter.com/JanssenUS. Janssen Biotech, Inc. and Janssen Research & Development, LLC are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding DARZALEX FASPRO®. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Biotech, Inc., or any of the other Janssen Pharmaceutical Companies, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 29, 2019, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
-  DARZALEX FASPRO® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
 Mayo Clinic. Amyloidosis overview: symptoms and causes. https://www.mayoclinic.org/diseases-conditions/amyloidosis/symptoms-causes/syc-20353178. Accessed January 2021.
 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.
 McCausland KL, et al. Patient. 2018;11(2):207-216.
 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.cycl%20ophosphamide.bortezomib.html?f=listing%3D0%2Abrowseby%3D8%2Asortby%3D1%2Amedia%3D3%2Ace_i. Accessed January 2021.
 Amyloidosis Foundation. AL amyloidosis facts. http://www.amyloidosis.org/facts/al/. Accessed January 2021.
 Mayo Clinic. Amyloidosis diagnosis and treatment. https://mayocl.in/3jK50G4. Accessed January 2021.
 Merlini G, et al. Light chain amyloidosis: the heart of the problem. Haematologica. 2013;98(10):1492-1495.
Source: Johnson & Johnson
Posted: January 2021
Darzalex Faspro (daratumumab and hyaluronidase-fihj) FDA Approval History