Skip to main content

FDA Approves Darzalex (daratumumab) in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible

HORSHAM, Pa., June 27, 2019 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the U.S. Food and Drug Administration (FDA) approval of Darzalex (daratumumab) in combination with lenalidomide and dexamethasone (Rd) for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The approval is based on results from the Phase 3 MAIA (MMY3008) clinical study, which showed that Darzalex-Rd significantly reduced the risk of disease progression or death by 44 percent compared to treatment with Rd alone.[i] The application received approval through the U.S. FDA’s Real-Time Oncology Review (RTOR) pilot program.

“Multiple myeloma can become more difficult to treat after relapse, so it is important that patients receive an efficacious upfront therapy with a goal of extending their first remission period,” said Saad Usmani, M.D., FACP, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, and a lead investigator of the MAIA study. “This regimen offers an important frontline treatment option for this patient population, and it has been submitted to the NCCN Multiple Myeloma Panel for review and consideration for potential inclusion in the NCCN Clinical Practice Guidelines.”

Data from the Phase 3 MAIA study were recently published in The New England Journal of Medicine and previously presented at the 2018 American Society of Hematology (ASH) Annual Meeting. At a median follow-up of 28 months, results showed Darzalex in combination with Rd significantly reduced the risk of disease progression or death by 44 percent in patients with newly diagnosed multiple myeloma who are transplant ineligible, compared to treatment with Rd alone (Hazard Ratio [HR] = 0.56; 95 percent confidence interval [CI]: 0.43-0.73; p<0.0001).[i] The median progression-free survival (PFS) for Darzalex-Rd has not yet been reached, compared to 31.9 months for patients who received Rd alone.1 The addition of Darzalex resulted in deeper responses compared to Rd alone, including increased rates of complete response (CR) or better (48 percent vs. 25 percent), very good partial response (VGPR) or better (79 percent vs. 53 percent) and overall response (93 percent vs. 81 percent).[i] Darzalex-Rd induced a >3-fold higher rate of minimal residual disease (MRD) negativity compared to Rd alone (24 percent vs. 7 percent).[i]

“For patients with multiple myeloma, optimizing response to frontline treatment is critical,” said Paul Giusti, President and CEO of the Multiple Myeloma Research Foundation. “This latest indication for Darzalex is a promising development for the myeloma community, and we are grateful to Janssen, our long-standing partner in myeloma research, as well as the patients with myeloma and healthcare providers involved in this study.”

"Today’s approval of Darzalex underscores the significant clinical benefit of this CD38 monoclonal antibody and our efforts to advance treatment paradigms to change the course of the disease," said Craig Tendler, M.D., Vice President, Clinical Development and Global Medical Affairs, Oncology, Janssen Research & Development, LLC. "Importantly, this milestone also highlights the efficiency of the FDA's Real-Time Oncology Review process, ensuring that proven treatment regimens, such as Darzalex plus lenalidomide and dexamethasone, are made available to patients as soon as possible."

The most frequent (≥20 percent) adverse reactions were infusion reactions, diarrhea, constipation, nausea, peripheral edema, fatigue, back pain, asthenia, pyrexia, upper respiratory tract infection, bronchitis, pneumonia, decreased appetite, muscle spasms, peripheral sensory neuropathy, dyspnea and cough.[i] Serious adverse reactions with a 2 percent greater incidence in the Darzalex-Rd arm compared to the Rd arm were pneumonia (15 percent vs. 8 percent), bronchitis (4 percent vs. 2 percent) and dehydration (2 percent vs. <1 percent), respectively.[i] Treatment-emergent Grade 3/4 hematology laboratory abnormalities (≥20 percent) were neutropenia (56 percent), lymphopenia (52 percent) and leukopenia (35 percent).1 The safety profile of Darzalex was consistent with that of previous studies.[i]

About the MAIA Trial

The randomized, open-label, multicenter Phase 3 study included 737 newly diagnosed patients with multiple myeloma ineligible for high-dose chemotherapy and ASCT aged 45-90 years old (median age of 73). Patients were randomized to receive either Darzalex-Rd or Rd alone in 28-day cycles. In the Darzalex-Rd treatment arm, patients received Darzalex 16 milligrams per kilogram (mg/kg) IV weekly for cycles 1 – 2, every two weeks for cycles 3 – 6 and every 4 weeks for cycle 7 and thereafter. Patients in the Darzalex-Rd and Rd treatment arms received 25 mg of lenalidomide on days 1 – 21 of each 28-day cycle, and dexamethasone at 40 mg once a week for each cycle. Patients in both treatment arms continued until disease progression or unacceptable toxicity.

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.[i] CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.[ii] Darzalex binds to CD38 and inhibits tumor cell growth causing myeloma cell death.[i] Darzalex may also have an effect on normal cells.[i] 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.[iii],[iv],[v],[vi],[vii],[viii],[ix],[x] 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.[xi],[xii]

In the U.S., 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 (PI) and an immunomodulatory agent, or who are double refractory to a PI and an immunomodulatory agent.[xiii] 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.[xiv] 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.[xv] 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 ASCT, making it the first monoclonal antibody approved for newly diagnosed patients with this disease.[xvi]

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.[xvii]

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.[xviii],[xix] When damaged, these plasma cells rapidly spread and replace normal cells with tumors in the bone marrow.[xix],[xx] 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.[xx] 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.[xxi]

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 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 the benefits of Darzalex® (daratumumab) for the treatment of patients with multiple myeloma. 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 Research & Development, LLC, 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 30, 2018, 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. Neither the Janssen Pharmaceutical Companies of Johnson & Johnson nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

  1. [i] Darzalex Prescribing Information, June 2019.
    [ii] 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.
    [iii] 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.
    [iv] 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.
    [v] 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&rank=2 NLM Identifier: NCT02541383.
    [vi] 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.
    [vii] 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.
    [viii] 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.
    [ix] 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
    [x] 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.
    [xi] 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/NCT02316106?term=smm2001&rank=1 Identifier: NCT02316106.
    [xii] 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
    [xiii] 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.
    [xiv] 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.
    [xv] 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.
    [xvi] 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.
    [xvii] Janssen Biotech, Inc. “Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab.” Issued August 30, 2012.
    [xviii] Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
    [xix] American Cancer Society. "What Is Multiple Myeloma?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed June 2019.
    [xx] American Cancer Society. “Key Statistics for Multiple Myeloma.” Available at: https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html. Accessed June 2019.
    [xxi] American Cancer Society. "Diagnosing Multiple Myeloma From Test Results." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed June 2019.

Source: Janssen Pharmaceutical Companies

Posted: June 2019

Related articles

Darzalex (daratumumab) FDA Approval History

More news resources

Subscribe to our newsletter

Whatever your topic of interest, subscribe to our newsletters to get the best of Drugs.com in your inbox.