DARZALEX® SC reduces admin­istra­tion time from hours to min­utes and dem­onstrates con­sis­tent ef­fi­cacy with a re­duc­tion in admin­istra­tion-related reac­tions com­pared to in­tra­venous DAR­ZA­LEX® (dara­tu­mu­mab)

Toronto, ON (Press Release) – The Janssen Pharma­ceu­tical Com­panies of John­son & John­son an­nounced to­day that Health Canada has approved DAR­ZA­LEX® SC (dara­tu­mu­mab), a new sub­cu­tane­ous for­mu­la­tion of dara­tu­mu­mab.¹ DAR­ZA­LEX® SC is approved in four regi­mens across five in­di­ca­tions in patients with mul­ti­ple myeloma, most notably newly diag­nosed, trans­plant-ineligible patients as well as re­lapsed or re­frac­tory patients. As a fixed-dose for­mu­la­tion, DAR­ZA­LEX® SC can be admin­istered over approx­i­mately three to five min­utes, sig­nif­i­cantly less time than in­tra­venous (IV) DAR­ZA­LEX®, which is admin­istered over hours.² DAR­ZA­LEX® SC is the only sub­cu­tane­ous CD38-directed anti­body approved in the treat­ment of mul­ti­ple myeloma.

In the Phase 3 COLUMBA study pub­lished in The Lancet, DAR­ZA­LEX® SC dem­onstrated a con­sis­tent over­all re­sponse rate (ORR) and phar­ma­co­ki­­net­ics and a similar safety profile com­pared with IV DAR­ZA­LEX® in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma. In addi­tion, there was a nearly two-thirds re­duc­tion in sys­temic admin­istra­tion-related reac­tions (ARRs) for DAR­ZA­LEX® SC com­pared to IV DAR­ZA­LEX® (13 per cent vs. 34 per cent, re­spec­tively).³

"DARZALEX® has be­come a back­bone ther­apy in the treat­ment of mul­ti­ple myeloma, sup­ported by a robust body of evi­dence in both the front­line and re­lapsed and re­frac­tory settings," says Dr. Darrell White, Hematologist, Queen Elizabeth II Health Sciences Centre, Halifax. "With this new sub­cu­tane­ous for­mu­la­tion, not only is treat­ment much more con­ve­nient for patients, but it will also play a very im­por­tant role in reducing wait times and the burden on our busy health­care sys­tem, especially during this time."

The ap­prov­al is based on data from the Phase 3 COLUMBA and Phase 2 PLEIADES stud­ies.^4,5 In the COLUMBA study, the ORR was non-inferior for patients taking DAR­ZA­LEX® SC as mono­therapy com­pared to those taking IV DAR­ZA­LEX® as mono­therapy (41 per cent vs. 37 per cent, re­spec­tively).⁶ Addi­tionally, in the Phase 2 PLEIADES study eval­u­ating the ef­fi­cacy and safety of DAR­ZA­LEX® SC in com­bi­na­tion ther­a­pies, objective re­sponses were dem­onstrated in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone (D-VMP) in newly diag­nosed trans­plant in­eli­gible patients. In addi­tion, objective re­sponses were dem­onstrated in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (D-Rd) in re­lapsed or re­frac­tory patients who re­ceived one prior line of ther­apy.⁷ In a pooled safety pop­u­la­tion of 490 patients who re­ceived DAR­ZA­LEX® SC as mono­therapy or in com­bi­na­tion, the ARR rate was 11 per cent.⁸

DARZALEX® SC is approved in all cur­rent IV in­di­ca­tions in­clud­ing (1) in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone in newly diag­nosed patients who are in­eli­gible for au­tol­o­gous stem cell trans­plant, (2) in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone in newly diag­nosed patients who are in­eli­gible for au­tol­o­gous stem cell trans­plant and in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma who have re­ceived at least one prior ther­apy, (3) in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone in patients who have re­ceived at least one prior ther­apy, and (4) as mono­therapy, in patients who have re­ceived at least three prior lines of ther­apy in­clud­ing a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory agent or who are double-refractory to a PI and an immuno­modu­la­tory agent.⁹

Active dis­cus­sions are on­go­ing with pub­lic insurers to de­ter­mine how DAR­ZA­LEX® SC can be made accessible for both re­lapsed or re­frac­tory patients as well as newly diag­nosed, trans­plant in­eli­gible patients.

"This ap­prov­al exemplifies Janssen's mis­sion and com­mitment to bringing to­geth­er passion, science and ingenuity to ad­vance novel solu­tions for patients," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Re­search & De­vel­op­ment, LLC.

About the COLUMBA Study

The ran­domised, open-label, multi­center Phase 3 COLUMBA study in­cluded 522 patients (median age of 67 years) with mul­ti­ple myeloma who had re­ceived at least three prior lines of ther­apy in­clud­ing a pro­te­a­some in­hib­i­tor (PI) and an immuno­modu­la­tory drug (IMiD), or whose dis­ease was re­frac­tory to both a PI and an ImiD. In the arm that re­ceived DAR­ZA­LEX® SC (n=263), patients re­ceived a fixed dose of DAR­ZA­LEX® SC 1,800 milligrams (mg), co-formulated with recombinant human hyal­uron­i­dase PH20 (rHuPH20) 2,000 Units per milliliter (U/mL), sub­cu­tane­ously weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and there­after. In the IV DAR­ZA­LEX® arm (n=259), patients re­ceived DAR­ZA­LEX® for IV in­fusion 16 milligrams per kilo­gram (mg/kg) weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and there­after. Each cycle was 28 days. In the arm that re­ceived DAR­ZA­LEX® SC, it was given in a fixed vol­ume of 15 mL over three to five min­utes; the median in­jec­tion time was five min­utes. In the arm that re­ceived the IV admin­istra­tion, the median durations of the first, sec­ond and sub­se­quent IV DAR­ZA­LEX® in­fusions were 7.0, 4.3 and 3.4 hours, re­spec­tively. Patients in both arms con­tinued treat­ment until dis­ease pro­gres­sion or un­ac­cept­able toxicity.^10,11

About the PLEIADES Study

The non-randomised, open-label, parallel assignment Phase 2 PLEIADES study in­cluded adults with mul­ti­ple myeloma, in­clud­ing 67 patients with newly diag­nosed mul­ti­ple myeloma who were treated with 1,800 mg of DAR­ZA­LEX® SC in com­bi­na­tion with bor­tez­o­mib, mel­phalan, and pred­ni­sone (D-VMP) and 65 patients with re­lapsed or re­frac­tory dis­ease who were treated with 1,800 mg of DAR­ZA­LEX® SC plus lena­lido­mide and dexa­meth­a­sone (D-Rd). The pri­mary end­point for the D-VMP and D- Rd cohorts was over­all re­sponse rate.¹²

About DAR­ZA­LEX® and DAR­ZA­LEX® SC

DARZALEX® is the first CD38-directed mono­clonal anti­body (mAb) approved to treat mul­ti­ple myeloma and in 2020, DAR­ZA­LEX® SC (dara­tu­mu­mab) follows as the only sub­cu­tane­ous CD38-directed anti­body approved to treat patients with mul­ti­ple myeloma.¹³ It binds to CD38, a surface pro­tein highly ex­pressed across mul­ti­ple myeloma cells.¹⁴ 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).¹⁵ DAR­ZA­LEX® has also dem­onstrated immuno­modu­la­tory effects such as in­creas­ing CD4+ and CD8+ T-cells counts, which may con­trib­ute to clin­i­cal re­sponse.¹⁶

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® and DAR­ZA­LEX® SC in Canada. For full Prescribing In­for­ma­tion and more in­for­ma­tion about DAR­ZA­LEX® and DAR­ZA­LEX® SC, please visit www.janssen.com/canada.

About Multiple Myeloma

Multiple myeloma is an incurable blood can­cer that affects a type of white blood cell called plasma cells, which are found in the bone mar­row.¹⁷ When damaged, these plasma cells rapidly spread and re­place nor­mal cells with tumors in the bone mar­row. In 2020, it is esti­mated that 3,400 Canadians will be diag­nosed with mul­ti­ple myeloma and there will be 1,600 deaths asso­ci­ated with the dis­ease.¹⁸ 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.¹⁹

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 a member of the Janssen Pharma­ceu­tical Com­panies of John­son & John­son.

*All trade­mark rights used under license.
**Dr. White 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® SC. 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 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 29, 2019, 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. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
2. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
3. Mateos MV, et al. Subcutaneous versus in­tra­venous dara­tu­mu­mab in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, ran­domised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.
4. Mateos M-V et al. Efficacy and Safety of the Randomized, Open-Label, Non-inferiority, Phase 3 Study of Subcutaneous (SC) Versus Intravenous (IV) Dara­tu­mu­mab (DARA) Admin­istra­tion in Patients (pts) With Re­lapsed or Re­frac­tory Multiple Myeloma (RRMM): COLUMBA. 2019 American Society of Clinical Oncology Annual Meeting. June 2019.
5. Janssen Re­search & De­vel­op­ment, LLC. A Study to Evaluate Subcutaneous Dara­tu­mu­mab in Com­bi­na­tion With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.
6. Mateos MV, et al. Subcutaneous versus in­tra­venous dara­tu­mu­mab in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, ran­domised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.
7. Chari A, M. J., McCarthy H, et al Subcutaneous dara­tu­mu­mab plus stan­dard treat­ment regi­mens in patients with mul­ti­ple myeloma across lines of ther­apy: PLEIADES study up­date. Poster pre­sented at: 61st American Society of He­ma­tol­ogy (ASH) Annual Meeting. Orlando, FL.
8. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
9. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
10. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
11. Mateos MV, et al. Subcutaneous versus in­tra­venous dara­tu­mu­mab in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, ran­domised, phase 3 trial [published online ahead of print March 23, 2020]. Lancet Haematol doi.org/10.1016/S2352-3026(20)30070-3.
12. Janssen Re­search & De­vel­op­ment, LLC. A Study to Evaluate Subcutaneous Dara­tu­mu­mab in Com­bi­na­tion With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.
13. Janssen Re­search & De­vel­op­ment, LLC. A Study to Evaluate Subcutaneous Dara­tu­mu­mab in Com­bi­na­tion With Standard Multiple Myeloma Treatment Regimens. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 [cited July 5, 2019]. Available at: https://clinicaltrials.gov/ct2/show/NCT03412565. Identifier: NCT03412565.
14. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
15. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
16. [DARZALEX® SC Product Monograph, Janssen Inc., July 29, 2020]
17. Kumar, SK et al. Risk of pro­gres­sion and sur­vival in mul­ti­ple myeloma relapsing after ther­apy with IMiDs and bor­tez­o­mib: a multi­center inter­na­tional myeloma work­ing group study. Leukemia. 2012 Jan; 26(1):149-57.
18. Canadian Cancer Society. "Signs and Symptoms of Multiple Myeloma." Available at: https://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/statistics/?region=on. Accessed June 2020.
19. 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 June 2020.

Source: Janssen.