Revised prod­uct label allows for new admin­istra­tion option

Horsham, PA (Press Release) – The Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson announced today that the U.S. Food and Drug Admin­istra­tion (FDA) has approved a split-dosing regi­men for DARZALEX® (dara­tu­mu­mab), providing health­care professionals and patients with multiple myeloma an option to split the first in­fusion over two consecutive days.¹ The U.S. FDA approval is based on data from the Phase 1b EQUULEUS (MMY1001) clin­i­cal study, which dem­onstrated DARZALEX phar­ma­co­ki­netic (PK) con­cen­tra­tions were com­parable at the end of weekly dosing, re­gard­less of whether the first dose was admin­istered as a split in­fusion or as a single in­fusion.¹

"The first in­fusion of DARZALEX is an im­por­tant first step in a patient's course of ther­apy, and this approval provides added flexibility for how patients may receive initial treat­ment," said Craig Tendler, M.D., Vice Pres­i­dent, Clinical Development and Global Medical Affairs, Janssen Research & Devel­op­ment, LLC. "We are committed to exploring options that may im­prove the over­all treat­ment ex­peri­ence for patients."

The U.S. FDA approval of a split-dosing regi­men for DARZALEX is based on data from the global, multi-arm, Phase 1b EQUULEUS (MMY1001) study in multiple myeloma, which eval­u­ated DARZALEX in com­bi­na­tion with various treat­ment regi­mens.¹ Splitting the first dose of DARZALEX over two consecutive days effectively reduced the duration of the first in­fusion and resulted in a similar rate and pattern of in­fusion reac­tions.¹ Data from the study dem­onstrated that DARZALEX con­cen­tra­tions were com­parable at the end of weekly dosing re­gard­less of whether the first 16 mg/kg dose was admin­istered as a split in­fusion or single first in­fusion.¹

The safety profile of DARZALEX was com­parable when admin­istered initially as a split or single dose, and no new safety events were observed with a split first dose.¹

This approval follows approvals in Canada and the European Union in December 2018 for the DARZALEX initial in­fusion split-dosing regi­men.

About DARZALEX (dara­tu­mu­mab) Injection for Intravenous Infusion

DARZALEX is the first and only CD38-directed anti­body to receive regu­la­tory approval to treat multiple myeloma.² In the U.S., DARZALEX (dara­tu­mu­mab) first received FDA approval in November 2015 as a mono­therapy for patients with multiple myeloma 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.³ DARZALEX received addi­tional approvals in November 2016 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.⁴ In June 2017, DARZALEX received approval in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for the treat­ment of patients with multiple myeloma who have received at least two prior ther­a­pies, in­­clud­ing lena­lido­mide and a PI.⁵ Most recently, in May 2018, DARZALEX received approval in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone for the treat­ment of patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­plant (ASCT), making it the first mono­clonal anti­body approved for newly diag­nosed patients with this disease.⁶

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered into a global license and devel­op­ment agree­ment, which granted Janssen an exclusive license to develop, manu­fac­ture and com­mer­cial­ize DARZALEX.⁷ For the full U.S. Prescribing Information, please visit www.DARZALEX.com.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^8,9 Refractory cancer occurs when a patient's disease is resistant to treat­ment or in the case of multiple myeloma, when patients progress within 60 days of their last ther­apy.^10,11 Relapsed cancer means the disease has returned after a period of initial, partial or com­plete remission.¹² In 2019, it is esti­mated that 32,110 people will be diag­nosed, and 12,960 will die from the disease, in the United States.¹³ While some patients with multiple myeloma have no symp­toms, most patients are diag­nosed due to symp­toms, which can in­clude bone fracture or pain, low red blood counts, fatigue, high cal­cium levels, kidney problems or in­fec­tions.¹⁴

IMPORTANT SAFETY INFORMATION²

CONTRAINDICATIONS

DARZALEX is con­tra­in­di­cated in patients with a history of severe hypersensitivity (eg, anaphylactic reac­tions) to dara­tu­mu­mab or any of the components of the for­mu­la­tion.

WARNINGS AND PRECAUTIONS

Infusion Reactions – DARZALEX can cause severe and/or serious in­fusion reac­tions, in­­clud­ing anaphylactic reac­tions. In clin­i­cal trials, approx­i­mately half of all patients ex­peri­enced an in­fusion reac­tion. Most in­fusion reac­tions occurred during the first in­fusion and were grade 1-2. Infusion reac­tions can also occur with sub­se­quent in­fusions. Nearly all reac­tions occurred during in­fusion or within 4 hours of com­plet­ing an in­fusion. Prior to the in­tro­duc­tion of post-infusion medication in clin­i­cal trials, in­fusion reac­tions occurred up to 48 hours after in­fusion. Severe reac­tions have occurred, in­­clud­ing bron­cho­spasm, hypoxia, dyspnea, hyper­tension, laryngeal edema and pul­mo­nary edema. Signs and symp­toms may in­clude res­pira­tory symp­toms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symp­toms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, and hypo­tension.

Pre-medicate patients with antihistamines, anti­pyretics, and corticosteroids. Frequently monitor patients during the entire in­fusion. Interrupt in­fusion for reac­tions of any severity and institute medical man­agement as needed. Permanently dis­con­tinue ther­apy if an anaphylactic reac­tion or life-threatening (Grade 4) reac­tion occurs and institute appro­pri­ate emergency care. For patients with Grade 1, 2, or 3 reac­tions, reduce the in­fusion rate when re-starting the in­fusion.

To reduce the risk of delayed in­fusion reac­tions, admin­ister oral corticosteroids to all patients fol­low­ing DARZALEX in­fusions. Patients with a history of chronic obstructive pul­mo­nary disease may require addi­tional post-infusion medications to man­age res­pira­tory com­pli­ca­tions. Consider pre­scrib­ing short- and long-acting bron­cho­di­lators and inhaled corticosteroids for patients with chronic obstructive pul­mo­nary disease.

Interference with Serological Testing – Dara­tu­mu­mab binds to CD38 on red blood cells (RBCs) and results in a pos­i­tive Indirect Antiglobulin Test (Indirect Coombs test). Dara­tu­mu­mab-mediated pos­i­tive indirect antiglobulin test may persist for up to 6 months after the last dara­tu­mu­mab in­fusion. Dara­tu­mu­mab bound to RBCs masks detection of anti­bodies to minor an­ti­gens in the patient's serum. The deter­mi­na­tion of a patient's ABO and Rh blood type are not impacted. Notify blood transfusion centers of this inter­fer­ence with serological testing and inform blood banks that a patient has received DARZALEX. Type and screen patients prior to starting DARZALEX.

Neutropenia – DARZALEX may in­­crease neu­tro­penia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­fac­turer's pre­scrib­ing in­for­ma­tion for back­ground ther­a­pies. Monitor patients with neu­tro­penia for signs of in­fec­tion. DARZALEX dose delay may be required to allow re­cov­ery of neu­tro­phils. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with growth factors.

Thrombocytopenia – DARZALEX may in­­crease thrombo­cytopenia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­fac­turer's pre­scrib­ing in­for­ma­tion for back­ground ther­a­pies. DARZALEX dose delay may be required to allow re­cov­ery of platelets. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with transfusions.

Interference with Determination of Complete Response – Dara­tu­mu­mab is a human IgG kappa mono­clonal anti­body that can be detected on both the serum protein electrophoresis (SPE) and immuno­fix­a­tion (IFE) assays used for the clin­i­cal monitoring of endogenous M-protein. This inter­fer­ence can impact the deter­mi­na­tion of com­plete response and of disease pro­gres­sion in some patients with IgG kappa myeloma protein.

Adverse Reactions – The most frequently reported adverse reac­tions (incidence ≥20%) in clin­i­cal trials were: in­fusion reac­tions, neu­tro­penia, thrombo­cytopenia, fatigue, nausea, diarrhea, con­sti­pa­tion, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizzi­ness, insomnia, cough, dyspnea, periph­eral edema, periph­eral sensory neu­rop­athy and upper res­pira­tory tract in­fec­tion.

In patients who received DARZALEX in com­bi­na­tion with bor­tez­o­mib, mel­phalan, and pred­ni­sone (DVMP), the most frequently reported adverse reac­tions (incidence ≥20%) were: upper res­pira­tory tract in­fec­tion (48%), in­fusion reac­tions (28%), and periph­eral edema (21%). Serious adverse reac­tions (≥2% com­pared to the VMP arm) were pneu­monia (11%), upper res­pira­tory tract in­fec­tion (5%), and pul­mo­nary edema (2%). Treatment-emergent Grade 3-4 hematology laboratory ab­nor­mal­i­ties ≥20% were lymphopenia (58%), neu­tro­penia (44%), and thrombo­cytopenia (38%).

In patients who received DARZALEX in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: upper res­pira­tory tract in­fec­tion (65%), in­fusion reac­tions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The over­all in­ci­dence of serious adverse reac­tions was 49%. Serious adverse reac­tions (≥2% com­pared to Rd) were pneu­monia (12%), upper res­pira­tory tract in­fec­tion (7%), influenza (3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory ab­nor­mal­i­ties ≥20% were neu­tro­penia (53%) and lymphopenia (52%).

In patients who received DARZALEX in com­bi­na­tion with bor­tez­o­mib and dexa­meth­a­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: periph­eral sensory neu­rop­athy (47%), in­fusion reac­tions (45%), upper res­pira­tory tract in­fec­tion (44%), diarrhea (32%), cough (27%), periph­eral edema (22%), and dyspnea (21%). The over­all in­ci­dence of serious adverse reac­tions was 42%. Serious adverse reac­tions (≥2% com­pared to Vd) were upper res­pira­tory tract in­fec­tion (5%), diarrhea (2%) and atrial fibrillation (2%). Treatment-emergent Grade 3-4 hematology laboratory ab­nor­mal­i­ties ≥20% were lymphopenia (48%) and thrombo­cytopenia (47%).

In patients who received DARZALEX in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone, the most frequent adverse reac­tions (>20%) were fatigue (50%), in­fusion reac­tions (50%), upper res­pira­tory tract in­fec­tion (50%), cough (43%), diarrhea (38%), con­sti­pa­tion (33%), dyspnea (33%), nausea (30%), muscle spasms (26%), back pain (25%), pyrexia (25%), insomnia (23%), arthralgia (22%), dizzi­ness (21%), and vomiting (21%). The over­all in­ci­dence of serious adverse reac­tions was 49%. Serious adverse reac­tions reported in ≥5% patients in­cluded pneu­monia (7%). Treatment-emergent hematology Grade 3-4 laboratory ab­nor­mal­i­ties ≥20% were anemia (30%), neu­tro­penia (82%), and lymphopenia (71%).

In patients who received DARZALEX as mono­therapy, the most frequently reported adverse reac­tions (incidence ≥20%) were: in­fusion reac­tions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper res­pira­tory tract in­fec­tion (20%). The over­all in­ci­dence of serious adverse reac­tions was 33%. The most frequent serious adverse reac­tions were pneu­monia (6%), general physical health deterioration (3%), and pyrexia (3%). Treatment-emergent Grade 3-4 hematology laboratory ab­nor­mal­i­ties ≥20% were lymphopenia (40%) and neu­tro­penia (20%).

DRUG INTERACTIONS

Effect of Other Drugs on Dara­tu­mu­mab: The coadministration of lena­lido­mide, poma­lido­mide or bor­tez­o­mib with DARZALEX did not affect the phar­ma­co­ki­netics of dara­tu­mu­mab.

Effect of Dara­tu­mu­mab on Other Drugs: The coadministration of DARZALEX with bor­tez­o­mib or poma­lido­mide did not affect the phar­ma­co­ki­netics of bor­tez­o­mib or poma­lido­mide.

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. Follow us at @JanssenGlobal and @JanssenUS. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson.

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 benefits of DARZALEX® (dara­tu­mu­mab) for the treat­ment of patients with multiple myeloma. 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 Research & Development, LLC, Janssen Biotech, Inc., and 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 31, 2017, 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, 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. Neither the Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson nor Johnson & Johnson under­takes to update any for­ward-looking state­ment as a result of new in­for­ma­tion or future events or devel­op­ments.

References

1. Janssen Research & Development, LLC. A Study of JNJ-54767414 (HuMax CD38) (Anti-CD38 Monoclonal Antibody) in Combination With Backbone Treatments for the Treatment of Patients With Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT01998971 Identifier: NCT01998971
2. DARZALEX Prescribing Information, June 2018.
3. Janssen Biotech, Inc. "DARZALEX® (dara­tu­mu­mab) Approved by U.S. FDA: First Human Anti-CD38 Monoclonal Antibody Available for the Treatment of Multiple Myeloma." Issued November 16, 2015.
4. Janssen Biotech, Inc. "DARZALEX® (dara­tu­mu­mab) Approved by U.S. FDA in Combination with Two Standard of Care Regimens for the Treatment of Patients with Multiple Myeloma Who Have Received At Least One Prior Therapy." Issued November 21, 2016.
5. Janssen Biotech, Inc. "DARZALEX® (dara­tu­mu­mab) Approved by the U.S. FDA in Combination with Pomalidomide and Dexamethasone for Patients with Multiple Myeloma Who Have Received At Least Two Prior Therapies." Issued June 16, 2017.
6. Janssen Pharma­ceu­tical Com­panies of Johnson & Johnson. "Janssen Announces DARZALEX® (dara­tu­mu­mab) U.S. FDA Approval for Newly Diagnosed Patients with Multiple Myeloma who are Transplant Ineligible." Issued May 7, 2018.
7. Janssen Biotech, Inc. "Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Dara­tu­mu­mab." Issued August 30, 2012.
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9. American Cancer Society. "What Is Multiple Myeloma?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 2018. Accessed February 2019.
10. National Cancer Institute. "NCI Dictionary of Cancer Terms: Refractory." Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245. Accessed February 2019.
11. Richardson, et al. "The Treatment of Relapsed and Refractory Multiple Myeloma." ASH Education Book. January 1, 2007 vol. 2007 no. 1 317-323.
12. National Cancer Institute. "NCI Dictionary of Cancer Terms: Relapsed." Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=45866. Accessed February 2019.
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Source: Janssen.