Janssen Announces Health Canada Approval of DARZALEX (daratumumab) in Combination with Lenalidomide and Dexamethasone for Newly Diagnosed Patients with Multiple Myeloma Who Are Transplant Ineligible

This DARZALEX®combination regimen reduced the risk of disease progression or death by 44% in newly diagnosed patients who are transplant ineligible

TORONTO, Oct. 30, 2019 /CNW/ - The Janssen Pharmaceutical Companies of Johnson & Johnson announced that Health Canada recently approved under Priority Review DARZALEX® (daratumumab), in combination with lenalidomide and dexamethasone (Rd), for newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The approval is based on results from the Phase 3 MAIA clinical study published in the New England Journal of Medicine, which showed the DARZALEX®-Rd combination reduced the risk of disease progression or death by 44 per cent compared to treatment with Rd alone.1

Multiple myeloma is an incurable blood cancer associated with the abnormal behaviour and uncontrolled growth of plasma cells in the bone marrow.2  Every day, approximately nine Canadians are diagnosed with multiple myeloma,3 but the cause or causes remain unknown4 and it can be difficult to diagnose.5 Advancements in research have led to the discovery of new therapies and combination therapies, providing hope for patients.6 Work is ongoing with both public and private insurers to determine how DARZALEX® can be made accessible for newly diagnosed, transplant ineligible patients.

"In multiple myeloma it is essential to administer the most effective therapy early, ideally as first line, to prevent disease relapse and the emergence of resistant clones. The use of daratumumab in combination with lenalidomide and dexamethasone resulted in unprecedented depth and durability of response with eradication of all detectable disease in a quarter of patients in the study," says Dr. Nizar Bahlis, Associate Professor, Cumming School of Medicine (CSM), University of Calgary and member of the CSM's Arnie Charbonneau Cancer Institute. "Based on the data, it is expected that this regimen should become the new standard to treat newly diagnosed transplant ineligible patients with multiple myeloma."

This marks the fourth approval for DARZALEX®. In June 2016, Health Canada approved DARZALEX® for those with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or who are refractory to both a PI and an IMiD (meaning they didn't respond to or relapsed while on those treatments).7 In April 2017, the medication was approved for use earlier in the disease - for patients who have received at least one prior therapy. For these patients, DARZALEX® is used in combination with either lenalidomide and dexamethasone, or with bortezomib and dexamethasone.8 In November 2018, the medication was approved in combination with bortezomib, melphalan and prednisone (VMP), for the treatment of newly diagnosed patients with multiple myeloma who are transplant ineligible.

The Health Canada approval of DARZALEX®-Rd is supported by data from the randomized, Phase 3 MAIA study. Results showed DARZALEX® in combination with Rd reduced the risk of disease progression or death by 44 per cent in patients with newly diagnosed multiple myeloma who are transplant ineligible compared to treatment with Rd alone (Hazard Ratio [HR] = 0.56; 95 per cent confidence interval [CI]: 0.43-0.73; p<0.0001).9 At a median follow-up of 28 months, 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.10, 11  The addition of DARZALEX® to Rd resulted in deeper responses compared to Rd alone, including increased rates of complete response (CR) or better (48 per cent vs. 25 per cent), very good partial response or better (79 per cent vs. 53 per cent) and overall response (93 per cent vs. 81 per cent).12 Twenty-four per cent of patients in the DARZALEX®-Rd group achieved CR or better and minimal residual disease (MRD) negativity status (10-5) compared to 7 per cent in the Rd group, representing a >3-fold higher rate.13

In the study, the most frequently reported Treatment Emergent Adverse Events (TEAEs) (≥20 per cent) in the DARZALEX®-Rd arm were: infusion-related reactions, diarrhea, neutropenia, constipation, fatigue, peripheral edema, anemia, back pain, asthenia, nausea, insomnia, muscle spasms, bronchitis, dyspnea, weight decreased, cough, peripheral sensory neuropathy, pyrexia, upper respiratory tract infection, pneumonia, decreased appetite, and hypokalemia.14 Serious TEAEs with a 2 per cent higher incidence in the DARZALEX®-Rd arm compared to the Rd arm were pneumonia (15 per cent vs 8 per cent) and bronchitis (4 per cent vs 2 per cent).15 Treatment-emergent Grade 3/4 hematology laboratory abnormalities (≥20 per cent) were neutropenia (56 per cent), lymphopenia (52 per cent) and leukopenia (35 per cent).16 The safety profile of DARZALEX® was generally consistent with that of previous studies.17

About Multiple Myeloma
Multiple myeloma is the most common plasma cell cancer18 and is characterized by an excess proliferation of plasma cells.19 In Canada, there were an estimated 3,317 new cases in 2019 and an estimated 1,563 deaths associated with the disease.20 While some patients with multiple myeloma have no symptoms in the early stages, patients are diagnosed due to symptoms that can include bone disease or pain, anemia, calcium elevation, and kidney problems.21

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).22,23 Patients were randomized to receive either DARZALEX®-Rd or Rd alone in 28-day cycles.24 In the DARZALEX®-Rd treatment arm, patients received DARZALEX® 16 milligrams per kilogram (mg/kg) through intravenous (IV) infusion weekly for cycles 1 - 2, every two weeks for cycles 3 - 6 and every 4 weeks for cycle 7 and thereafter.25 Patients in both 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.26

About DARZALEX® (daratumumab)
DARZALEX® is the first CD38-directed monoclonal antibody (mAb) approved to treat multiple myeloma. It binds to CD38, a surface protein highly expressed across multiple myeloma cells.27 DARZALEX® induces tumor cell death through cell lysis via multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).28  DARZALEX® has also demonstrated immunomodulatory effects such as increasing CD4+ and CD8+ T-cells counts, which may contribute to clinical response. 29 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.30,31

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize DARZALEX®. Janssen Inc. commercializes DARZALEX® in Canada. For full Prescribing Information and more information about DARZALEX®, please visit www.janssen.com/canada.

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/canada. Follow us at @JanssenCanada. Janssen Inc. is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.

*Dr. Bahlis was not compensated for any media work. He has been compensated as a consultant.

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®. 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 Inc., 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. 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.

References:
______________________________________

1 The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
2 Myeloma Canada. "What Is Multiple Myeloma?" Available at: https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma. Accessed October 2019.
3 Canadian Cancer Society. "Canadian Cancer Statistics 2019." Available at: https://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2019-EN.pdf?la=en. Accessed September 2019.
4 Myeloma Canada. "What Is Multiple Myeloma?" Available at: https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma. Accessed October 2019.
5 Multiple Myeloma Research Foundation. "Diagnosis." Available at: https://themmrf.org/multiple-myeloma/diagnosis/. Accessed October 2019.
6 Myeloma Canada. "What Is Multiple Myeloma?" Available at: https://www.myelomacanada.ca/en/about-multiple-myeloma/what-is-myeloma. Accessed October 2019.
7 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
8 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
9 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
10 [DARZALEX™ Product Monograph, Janssen Inc., October 25, 2019]
11 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
12 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
13 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
14 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
15 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
16 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
17 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
18 Canadian Cancer Society. "Types of Multiple Myeloma," Available at: http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/types-of-multiple-myeloma/?region=on. Accessed September 2019.
19 Canadian Cancer Society. "What Is Multiple Myeloma?" Available at: https://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/multiple-myeloma/?region=on. Accessed September 2019.
20 Canadian Cancer Society. "Canadian Cancer Statistics 2019." Available at: https://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2019-EN.pdf?la=en. Accessed September 2019.
21 Canadian Cancer Society. "Signs and Symptoms of Multiple Myeloma." Available at: http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/signs-and-symptoms/?region=on. Accessed November 2018.
22 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
23 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
24 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
25 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
26 [The New England Journal of Medicine. "Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma." Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa1817249. Accessed September 2019.
27 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
28 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
29 [DARZALEX® Product Monograph, Janssen Inc., October 25, 2019]
30 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.
31 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&=1 Identifier: NCT02413489.

SOURCE Janssen Inc.

For further information: Media Contact: Janssen Inc., Jennifer McCormack, Office: (416) 382-5121; Investor Contact: Lesley Fishman, Office: (732) 524-3922

http://www.janssen.ca/

To read more Press Release articles, click here.