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

Toronto, ON (Press Release) – 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

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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.
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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.
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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.
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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.