DARZALEX® com­bi­na­tion ther­apy sig­nif­i­cantly im­proved pro­gres­sion-free survival (PFS) com­pared to standard of care regi­mens alone

Toronto, ON (Press Release) – Janssen Inc. announced today that Health Canada has approved DARZALEX® (dara­tu­mu­mab), 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.¹ Due to the high unmet medical need for multiple myeloma patients, DARZALEX® was granted a Priority Review by Health Canada for this sub­mission.

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^2,3 The dis­ease can be very complex to treat as most patients relapse or be­come resistant to standard ther­a­pies, making the approval of new treat­ment options so im­por­tant.^4,5 Janssen looks for­ward to work­ing with insurers to de­ter­mine how DARZALEX® can be made avail­able for patients through both private and public insurance plans.

In June 2016, Health Canada issued a Notice of Compliance with Conditions (NOC/c) approving 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 treat­ment).⁶ With this new approval, patients can now use DARZALEX® treat­ment earlier in their dis­ease.

"Canadians living with multiple myeloma have had good reason for hope in recent years with the Health Canada approvals of new treat­ments like DARZALEX®," says Aldo Del Col, Co-Founder and Chairman, Myeloma Canada. "While this is en­cour­ag­ing, it is just a first step. There are hurdles to overcome before funding and access to these new treat­ments are approved by gov­ern­ment drug plans."

Data from two Phase 3 studies sup­ported this new approval. They in­clude the open-label, ran­dom­ized clin­i­cal studies POLLUX (MMY3003) and CASTOR (MMY3004). POLLUX was published in The New England Journal of Medicine, with an accompanying editorial, in Octo­ber 2016⁷; and CASTOR was published in The New England Journal of Medicine in August 2016.⁸

POLLUX showed that DARZALEX®, in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, sig­nif­i­cantly im­proved pro­gres­sion free survival (PFS) com­pared to lena­lido­mide and dexa­meth­a­sone alone.⁹ While the median PFS had not been reached in patients treated with DARZALEX® in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, it was 18.4 months for patients treated with lena­lido­mide and dexa­meth­a­sone alone. The PFS hazard ratio (HR) was 0.37 (99.39 per cent CI: 0.23, 0.59; p<0.0001), rep­re­senting a 63 per cent reduction in the risk of dis­ease pro­gres­sion or death in patients treated in the DARZALEX® arm.¹⁰ The study also showed that DARZALEX® used in com­bi­na­tion sig­nif­i­cantly in­creased the over­all response rate (ORR) (91 per cent vs. 75 per cent, p<0.0001), com­pared to lena­lido­mide and dexa­meth­a­sone alone, also doubling rates of stringent com­plete response (sCR) (18 per cent vs. 7 per cent) and com­plete response (CR) (25 per cent vs. 12 per cent), and in­creas­ing very good partial response (VGPR) (32 per cent vs. 24 per cent).¹¹

The second study, CASTOR, found the median PFS had not been reached in patients treated with DARZALEX® in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone and was 7.2 months in the bor­tez­o­mib and dexa­meth­a­sone arm. The PFS hazard ratio (HR) was 0.39 (98.98% CI: 0.26, 0.58; p-value < 0.0001), rep­re­senting a 61 per cent reduction in the risk of dis­ease pro­gres­sion or death for patients in the DARZALEX® arm.¹² DARZALEX® used in com­bi­na­tion was also shown to sig­nif­i­cantly in­crease ORR (79 per cent vs. 60 per cent, p<0.0001), com­pared to bor­tez­o­mib and dexa­meth­a­sone alone, also doubling rates of sCR (4 per cent vs. 2 per cent), CR (14 per cent vs. 7 per cent), and VGPR (38 per cent vs. 19 per cent).¹³

"Having more options in the treat­ment of multiple myeloma is incredibly im­por­tant," says Dr. Michael Sebag, Hematologist at the McGill University Health Centre.* "Not only can DARZALEX® be used as a single agent, but clin­i­cal data now show sig­nif­i­cant efficacy in im­proved pro­gres­sion-free survival when it is used in com­bi­na­tion with two of the most widely used treat­ment classes. This makes it a versatile option for patients who have received at least one prior ther­apy."

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®.¹⁴

About Multiple Myeloma

Multiple myeloma is the most common plasma cell cancer¹⁵ and is char­ac­ter­ized by an excess pro­lif­er­a­tion of plasma cells.¹⁶ In Canada, there were an esti­mated 2,700 new cases in 2016 and an esti­mated 1,450 deaths asso­ci­ated with the dis­ease.¹⁷ While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms that can in­clude bone fractures or pain, low blood counts, cal­cium elevation, and kidney problems.¹⁸

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.¹⁹ 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).²⁰ DARZALEX® has also dem­onstrated immuno­modu­la­tory effects such as in­creas­ing CD4+ and CD8+ T-cells counts, which may con­trib­ute to clin­i­cal response.²¹

Overall, the safety of the DARZALEX® com­bi­na­tion ther­apy was con­sis­tent with the known safety profiles of DARZALEX® mono­therapy (D) and lena­lido­mide plus dexa­meth­a­sone (Rd), re­spec­tive­ly. In data from the POLLUX trial, the most frequent (≥20 per cent) treat­ment-emergent adverse events (TEAEs) [DRd/Rd] were in­fusion reac­tions (48 per cent/0 per cent), diarrhea (47 per cent/28 per cent), nausea (25 per cent/16 per cent), fatigue (35 per cent/29 per cent), pyrexia (21 per cent/11 per cent), upper res­pira­tory tract in­fec­tion (69 per cent/52 per cent), muscle spasms (27 per cent/20 per cent), cough (32 per cent/15 per cent), dyspnea (23 per cent/14 per cent), con­sti­pa­tion (30 per cent/26 per cent), anemia (34 per cent/36 per cent), neu­tro­penia (60 per cent/44 per cent) and thrombo­cyto­penia (28 per cent/30 per cent).²²

In data from the CASTOR study, the safety of the DARZALEX® com­bi­na­tion ther­apy was con­sis­tent with the known safety profiles of DARZALEX® mono­therapy (D) and bor­tez­o­mib plus dexa­meth­a­sone (Vd), re­spec­tive­ly. The most frequent TEAEs [DVd/Vd] (>20 per cent) were in­fusion reac­tions (45 per cent/0 per cent), diarrhea (34 per cent/22 per cent), periph­eral edema (24 per cent/14 per cent), upper res­pira­tory tract in­fec­tion (49 per cent/31 per cent), periph­eral sensory neu­rop­athy (49 per cent/38 per cent), cough (30 per cent/14 per cent), dyspnea (21 per cent/11 per cent), thrombo­cyto­penia (60 per cent/44 per cent), anemia (28 per cent/32 per cent) and fatigue (22 per cent/25 per cent).²³

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. Michael Sebag was not compensated for any media work. He has been a paid con­sul­tant to Janssen Inc.

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 efficacy and avail­a­bil­ity of DARZALEX® (dara­tu­mu­mab). 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., 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 obtaining funded access to DARZALEX® for patients; 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 or financial distress 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 Jan­u­ary­ 1, 2017, in­clud­ing in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," 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.

References

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Source: Janssen.