A new ther­apy providing an im­por­tant option for multiple myeloma patients who have received three or more prior lines of ther­apy

Toronto, Canada (Press Release) – Janssen Inc. announced today Health Canada has issued a Notice of Compliance with Conditions (NOC/c) approving DARZALEX™ (dara­tu­mu­mab) for the treat­ment of patients 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. Health Canada approved this prod­uct on the con­di­tion that Janssen Inc. carries out con­firmatory trials to verify the clin­i­cal benefit of DARZALEX™.¹

Multiple myeloma is an incurable blood cancer that can be very complex to treat. Most patients relapse or be­come resistant to standard ther­a­pies, which makes the approval of new treat­ment options so im­por­tant.^2,3 DARZALEX™ is a first-in-class, fully human mono­clonal anti­body (mAb), targeting CD38, a surface protein highly ex­pressed across multiple myeloma cells.⁴ DARZALEX™ inhibits the growth of CD38-expressing tumour cells, and may utilize multiple effector functions resulting in immune-mediated tumour cell death.

"The clin­i­cal data showed striking efficacy and safety for patients with multiple myeloma who have tried and failed on other avail­able treat­ment options," says Dr. Darrell White, Hematologist, Queen Elizabeth II Health Sciences Centre, Halifax.* "DARZALEX™ fills a critical unmet need in the treat­ment of this dev­as­tat­ing disease because it works using a mech­a­nism of action that is unique among other approved ther­a­pies."

The NOC/c policy provides access to promising new drugs for patients suffering from serious, life-threatening or severely debilitating diseases, or con­di­tions for which no drug is cur­rently mar­keted in Canada, or for which a sig­nif­i­cant in­­crease in efficacy or sig­nifi­cant de­crease in risk is dem­onstrated in rela­tion­ to existing drugs mar­keted in Canada.⁵ The DARZALEX™ approval with con­ditions was based on the pri­mary efficacy end­point of over­all response rate dem­onstrated in the Phase 2 single-arm SIRIUS study that was published in The Lancet in 2016. The study enrolled patients with multiple myeloma who had received at least three prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent (IMiD), or were double refractory to a PI and an IMiD.⁶ The data showed DARZALEX™demonstrated a 29 per cent over­all response rate and a tolerable safety profile in these heavily pre-treated patients.⁷

The approval was also sup­ported by data from other studies, in­­clud­ing the multi-centre, two-part open-label Phase 1/2 GEN501 mono­therapy study published in The New England Journal of Medicine in September 2015. This study enrolled patients with multiple myeloma who had a relapse after, or had disease that was refractory to, two or more dif­fer­en­t prior ther­a­pies, in­­clud­ing IMiDs, PIs, chemo­ther­apy, and au­tol­o­gous stem-cell trans­plan­ta­tion. The study showed DARZALEX™ dem­onstrated a tolerable safety profile and a 36 per cent over­all response rate in patients treated with a 16 mg/kg dose, with responses deepening over time.⁸

"The reality is multiple myeloma is an incurable cancer and despite treat­ment ad­vances, most patients relapse or be­come resistant to avail­able ther­a­pies," says Aldo Del Col, Co-Founder and Chairman, Myeloma Canada. "That unfortunate reality means patients are eventually left without options. For the in­creas­ing number of Canadians living with myeloma, this news provides hope for urgently-needed new treat­ment options that will im­prove patient out­comes while providing a good quality of life. The patient com­munity is there­fore very excited about the approval of DARZALEX™ as a new, effective treat­ment option to turn to."

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™.

About Multiple Myeloma

Multiple myeloma is the most common plasma cell cancer⁹ and is char­acterized by an excess proliferation of plasma cells.¹⁰ In Canada, there were an esti­mated 2,700 new cases in 2015 and an esti­mated 1,400 deaths asso­ci­ated with the disease.¹¹ While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone fractures or pain, low blood counts, cal­cium elevation, and kidney problems.¹²

About DARZALEX™ (dara­tu­mu­mab)

DARZALEX™ is the first CD38-directed mono­clonal anti­body (mAb) to be approved to treat multiple myeloma. It binds to CD38, a surface protein highly ex­pressed across multiple myeloma cells.¹³ DARZALEX™ induces tumour 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).¹⁴ DARZALEX™ has also dem­onstrated immuno­modu­la­tory effects such as in­creas­ing CD4+ and CD8+ T-cells counts, which may con­trib­ute to clin­i­cal response.¹⁵

Infusion-related reac­tions (IRR) were the most frequently observed treat­ment-emergent adverse events (TEAEs) and occurred in 48 per cent of patients treated at 16 mg/kg. Almost all IRRs (95 per cent) occurred at the first in­fusion and were mainly Grade 1 or 2.16 Severe in­fusion-related reac­tions were observed in 3 per cent of patients, and in­cluded broncho­spasm, dyspnea, hypoxia and hyper­tension.¹⁷

Other frequently reported TEAEs (incidence ≥20 per cent) were: fatigue, nausea, back pain, pyrexia, cough, anemia, neu­tro­penia, thrombo­cyto­penia, and upper res­pira­tory tract in­fec­tion.¹⁸ Four per cent of patients dis­con­tinued treat­ment due to TEAEs.¹⁹ The most common (≥ 2 per cent) serious TEAEs were pneu­monia (6 per cent), general physical health deterioration, hyper­calcemia and pyrexia (each at 3 per cent), cross-match incompatible and herpes zoster (each at 2 per cent).²⁰

More in­­for­ma­tion about DARZALEX™ is avail­able at www.janssen.com/canada.

About the Janssen Pharma­ceu­tical Com­panies

At the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson, we are work­ing to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease in­spires us. We bring together the best minds and pursue the most promising science. We are Janssen. We col­lab­o­rate with the world for the health of everyone in it. Learn more at www.janssen.com/canada. Follow us on Twitter at @JanssenCanada.

*Dr. White was not compensated for any media work. He has been a paid consultant to Janssen Inc.

References

1. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
2. Kumar, SK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516–20.
3. Turesson, I et al. Patterns of improved survival in patients with multiple myeloma in the twenty-first century: a population-based study. J Clin Oncol 2010;28: 830–34.
4. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
5. Health Canada. "Guidance Document: Notice of Compliance with Conditions (NOC/c)," Available at: http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/compli-conform/noccg_accd-eng.php.Accessed September 2015.
6. Lonial, S et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. The Lancet. Volume 387, Issue 10027, 9–15 April 2016, p1551–1560. Available online at: http://thelancet.com/journals/lancet/article/PIIS0140-6736(15)01120-4/fulltext. Accessed May 2016.
7. Lonial, S et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. The Lancet. Volume 387, Issue 10027, 9–15 April 2016, p1551–1560. Available online at: http://thelancet.com/journals/lancet/article/PIIS0140-6736(15)01120-4/fulltext. Accessed May 2016.
8. Lokhorst, HM et al. New England Journal of Medicine, "Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma." September 24, 2015DOI: 10.1056/NEJMoa1506348. Available at: http://www.nejm.org/doi/full/10.1056/NEJMoa1506348. Accessed September 2015.
9. 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 2015.
10. American Cancer Society. "Multiple Myeloma Overview" http://www.cancer.net/cancer-types/multiple-myeloma/overview. Accessed June 2015.
11. Canadian Cancer Society. "Canadian Cancer Statistics 2015." Available at https://www.cancer.ca/~/media/cancer.ca/CW/cancer%20information/cancer%20101/Canadian%20cancer%20statistics/Canadian-Cancer-Statistics-2015-EN.pdf. Accessed September 2015.
12. 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 September 2015.
13. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
14. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
15. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
16. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
17. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
18. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
19. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]
20. [DARZALEX™ Product Monograph, Janssen Inc., June 29, 2016]

Cautions Regarding Forward-Looking Statements

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing ex­pec­ta­tions for 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. 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 con­tinued clin­i­cal success and 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 to appli­­cable laws and reg­u­la­tions, in­­clud­ing 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 January 3, 2016, in­­clud­ing in Exhibit 99 thereto, 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 or Johnson & Johnson under­takes to update any for­ward-looking state­ment as a result of new in­­for­ma­tion or future events or devel­op­ments.

Source: Janssen Inc.