DARZALEX® com­bi­na­tion ther­apy sig­nif­i­cantly reduced the risk of dis­ease pro­gres­sion or death com­pared to a preferred regi­men alone.^1,2

Toronto, ON (Press Release) – The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson announced today that Health Canada has approved DARZA­LEX® (dara­tu­mu­mab), in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone (VMP), for the treat­ment of patients newly diag­nosed with multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plan­ta­tion.³ DARZA­LEX® is the first mono­clonal anti­body to be approved for newly diag­nosed patients in Canada.

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^4,5 The dis­ease can be very complex to treat as most patients relapse or be­come resistant to standard ther­a­pies, but with in­creas­ing research and treat­ment ad­vances, the outlook for patients is im­prov­ing.^6,7,8 Eight Canadians are diag­nosed each day, with an average age of diag­nosis in the mid-sixties.⁹ Work is ongoing with both public and private insurers to de­ter­mine how DARZA­LEX® can be accessible for newly diag­nosed, trans­plant in­eli­gible patients.

"This dara­tu­mu­mab com­bi­na­tion regi­men for newly diag­nosed patients who don't qualify for a trans­plant can result in lower risk of dis­ease pro­gres­sion and higher rates of response," says Dr. Darrell White, Hematologist, Queen Elizabeth II Health Sciences Centre. "The data sup­ports this regi­men as an effective new option for this patient pop­u­la­tion."

This marks the third indi­ca­tion 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).¹⁰ 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.¹¹ DARZALEX® is now publicly funded in the province of Québec for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy.

The Health Canada approval of DARZALEX® in com­bi­na­tion with VMP is sup­ported by data from the ran­dom­ized, open-label, multi­center Phase 3 ALCYONE (MMY3007) study, published in the New England Journal of Medicine. The com­bi­na­tion of DARZALEX® with VMP reduced the risk of dis­ease pro­gres­sion or death by 50 per cent, com­pared to treat­ment with VMP alone (Hazard Ratio [HR] = 0.50; 95 per cent con­fi­dence in­ter­val (CI) [0.38-0.65], p<0.0001).¹² The median pro­gres­sion-free survival (PFS) for DARZALEX® in com­bi­na­tion with VMP had not yet been reached, com­pared to a median PFS of 18.1 months for patients who received VMP alone.¹³

Treatment with DARZALEX® in com­bi­na­tion with VMP sig­nif­i­cantly im­proved over­all response rates (90.9vs. 73.9%) com­pared to VMP alone.¹⁴ Additionally, measures of stringent com­plete response (18 vs. 7%), com­plete response (24.6 vs.17.4%) and very good partial response (28.6 vs. 25.3%) all showed marked im­prove­ment.¹⁵ Patients receiving DARZALEX® in com­bi­na­tion with VMP achieved a more than three-fold in­crease in the minimal residual dis­ease (MRD) negativity rate (21.1 vs. 6.2%) com­pared to those who received VMP alone.¹⁶

In the study, the most frequently reported Treatment Emergent Adverse Events (TEAEs) (≥20%) in the DARZALEX®-VMP (D-VMP) arm were: in­fusion-related reac­tions, neu­tro­penia, thrombo­cyto­penia, anemia, upper res­pira­tory tract in­fec­tion, pyrexia, diarrhea, nausea, and periph­eral sensory neu­rop­athy.¹⁷ The over­all in­ci­dence of serious TEAEs was 41.6% in the D-VMP arm and 32.5% in the VMP arm.18 Serious TEAEs (≥2%) with at least a 2% higher in­ci­dence in the D-VMP arm com­pared to the VMP arm in­cluded in­fec­tions (23.1% vs 11.9%), in­clud­ing pneu­monia (D-VMP 10.1% vs VMP 3.1%).¹⁹ Infusion-related reac­tions were reported in 27.7% of patients in the D-VMP group.²⁰ Treatment-emergent hematology laboratory ab­nor­mal­i­ties for D-VMP vs. VMP were lymphopenia (85% vs. 83%), neu­tro­penia (86% vs. 87%), thrombo­cyto­penia (88% vs. 88%) and anemia (47% vs. 50%).²¹ The warnings and precautions for DARZALEX® in­clude in­fusion reac­tions, in­fec­tions, inter­fer­ence with indirect antiglobulin test, inter­fer­ence with deter­mi­na­tion of com­plete response, neu­tro­penia, thrombo­cyto­penia and in­fec­tions.22

About Multiple Myeloma

Multiple myeloma is the most common plasma cell cancer23 and is char­ac­ter­ized by an excess pro­lif­er­a­tion of plasma cells.²⁴ In Canada, there were an esti­mated 2,900 new cases in 2017 and an esti­mated 1,450 deaths asso­ci­ated with the dis­ease.²⁵ While some patients with multiple myeloma have no symp­toms in the early stages, most patients are diag­nosed due to symp­toms that can in­clude bone dis­ease or pain, anemia, cal­cium elevation, and kidney problems.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 to eval­u­ate DARZALEX® in com­bi­na­tion with standard of care regi­mens for newly diag­nosed patients who are eli­gible and in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT).

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 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 at @JanssenCanada. Janssen Inc. is part of the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson.

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

References

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Source: Janssen.