• FDA action underscores poten­tial clin­i­cal benefit of dara­tu­mu­mab as a back­bone ther­apy in com­bi­na­tion with either a pro­te­a­some inhibitor (PI) or an immuno­modu­latory agent for patients who have received at least one prior ther­apy
• Marks the second Break­through Therapy Desig­na­tion for dara­tu­mu­mab

Raritan, NJ (Press Release) – The U.S. Food and Drug Admin­istra­tion (FDA) has granted a Break­through Therapy Desig­na­tion to the immuno­therapy dara­tu­mu­mab (DARZALEX®) in com­bi­na­tion with lena­lido­mide (an immuno­modu­la­tory agent) and dexa­metha­sone, or bor­tez­o­mib (a pro­te­a­some inhibitor [PI]) and dexa­metha­sone, for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy, Janssen Research & Development, LLC announced today. This marks the second time dara­tu­mu­mab has received a Break­through Therapy Desig­na­tion, which is in­tended to expedite the devel­op­ment and review timelines of poten­tial new med­i­cines to treat serious or life-threatening diseases, where pre­lim­i­nary clin­i­cal evi­dence shows that the med­i­cine may provide sub­stan­tial im­prove­ment over existing ther­a­pies.¹ Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^2,3

"Despite tremendous progress in the past 15 years, multiple myeloma remains a highly complex and dif­fi­cult disease to treat, with most patients relapsing or becoming resistant to ther­apy," said MMY3003 (POLLUX) lead study author Meletios A. Dimopoulos, M.D., Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece. "Daratumumab has already shown pronounced activity as a mono­therapy in heavily pre-treated patients. This desig­na­tion underscores the poten­tial of dara­tu­mu­mab in com­bi­na­tion with either a pro­te­a­some inhibitor or an immuno­modu­la­tory agent to provide much-needed benefit to patients with at least one prior ther­apy."

Breakthrough Therapy Desig­na­tion was granted to dara­tu­mu­mab based on data from two Phase 3 studies:

• The MMY3004 (CASTOR) clinical trial evaluating daratumumab in combination with bortezomib and dexa­metha­sone, compared to bortezomib and dexa­metha­sone alone, in patients with multiple myeloma who received at least one prior therapy. Overall, the daratumumab combination therapy demonstrated a reduction in the risk of disease progression or death.
  • These results were presented at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in June 2016. More information can be found at www.ClinicalTrials.gov (NCT02136134).
• The MMY3003 (POLLUX) clin­i­cal trial eval­u­ating dara­tu­mu­mab in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, com­pared to lena­lido­mide and dexa­metha­sone alone, in patients with multiple myeloma who received at least one prior ther­apy. Overall, the addi­tion of dara­tu­mu­mab reduced the risk of disease pro­gres­sion or death in these patients.
  • These results were presented at the 21st Annual Congress of the European Hematology Association (EHA) in June 2016. More in­­for­ma­tion can be found at www.ClinicalTrials.gov (NCT02076009).

"We are pleased that the FDA has granted a second Break­through Therapy Desig­na­tion to dara­tu­mu­mab. This is an im­por­tant recognition of the transformative poten­tial of dara­tu­mu­mab and its possible benefit as a back­bone ther­apy in com­bi­na­tion with two of the most widely used regi­mens for multiple myeloma," said Craig L. Tendler, M.D., Vice Pres­i­dent, Late-Stage Development and Global Medical Affairs for Oncology, Hematology and Supportive Care, Janssen Research & Development, LLC. "We look for­ward to work­ing closely with the FDA through­out the review process and remain committed to exploring the full clin­i­cal benefit of this promising com­­pound for multiple myeloma patients who are eagerly awaiting new treat­ment options."

In November 2015, dara­tu­mu­mab (DARZALEX®) was approved by the FDA for the treat­ment of patients with multiple myeloma who have received at least three prior lines of ther­apy, in­­clud­ing a PI and an immuno­modu­la­tory agent, or who are double-refractory to a PI and an immuno­modu­la­tory agent. This indi­ca­tion is approved under accelerated approval based on response rate. Continued approval for this indi­ca­tion may be contingent upon veri­fi­ca­tion and description of clin­i­cal benefit in a con­firmatory trial.⁴ In May 2013, dara­tu­mu­mab received Break­through Therapy Desig­na­tion from the FDA for this indi­ca­tion.

In May 2016, the European Com­mis­sion (EC) granted con­di­tional approval to DARZALEX for mono­therapy of adult patients with re­lapsed and refractory multiple myeloma, whose prior ther­apy in­cluded a PI and an immuno­modu­la­tory agent and who have dem­onstrated disease pro­gres­sion on the last ther­apy.

About DARZALEX® (dara­tu­mu­mab)

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous use is the first CD38-directed mono­clonal anti­body (mAb) approved any­where in the world.⁴ CD38 is a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of disease stage.⁵ Dara­tu­mu­mab is believed to induce tumor cell death through multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­tox­icity (CDC), anti­body-dependent cellular cyto­tox­icity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP), as well as through apop­tosis, in which a series of molecular steps in a cell lead to its death.⁴ Dara­tu­mu­mab is also believed to induce tumor cell death through immuno­modu­la­tory effects, according to a study recently presented at the 57th Annual Meeting and Exposition of the American Society of Hematology (ASH).⁶ DARZALEX is being eval­u­ated in a com­pre­hen­sive clin­i­cal devel­op­ment pro­gram that in­cludes five Phase 3 studies across a range of treat­ment settings in multiple myeloma, such as in frontline and re­lapsed settings. Additional studies are ongoing or planned to assess its poten­tial in other malignant and pre-malignant diseases in which CD38 is ex­pressed, such as smol­der­ing myeloma, non-Hodgkin's lym­phoma and a solid tumor indi­ca­tion. DARZALEX was the first mAb to receive regu­la­tory approval to treat re­lapsed or refractory multiple myeloma.⁴

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. DARZALEX is com­mer­cial­ized in the U.S. by Janssen Biotech, Inc. For more in­­for­ma­tion, 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.^7,8 Refractory cancer occurs when a patient's disease is resistant to treat­ment or in the case of multiple myeloma, patients progress within 60 days of their last ther­apy.^9,10 Relapsed cancer means the disease has returned after a period of initial, partial or com­plete remission.^7,11 Accounting for approx­i­mately one per­cent of all cancers and 15 per­cent to 20 per­cent of haematologic malig­nan­cies world­wide, multiple myeloma is designated as an orphan disease in both the U.S. and Europe.¹¹ Globally, it is esti­mated that 124,225 people were diag­nosed, and 87,084 died from the disease in 2015.^12,13 While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone fracture or pain, low red blood counts, fatigue, cal­cium elevation, kidney problems or in­fec­tions.¹⁴ Patients who relapse after treat­ment with standard ther­a­pies (including PIs or immuno­modu­la­tory agents) typically have poor prognoses and few remaining options.³

DARZALEX® (dara­tu­mu­mab) Important Safety Information – Professional

CONTRAINDICATIONS - None

WARNINGS AND PRECAUTIONS

Infusion Reactions – DARZALEX® can cause severe in­fusion reac­tions. Approx­i­mately half of all patients ex­peri­enced a reac­tion, most during the first in­fusion. 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, and hyper­tension. Signs and symp­toms may in­clude res­pira­tory symp­toms, such as cough, wheezing, larynx and throat tight­ness and irritation, laryngeal edema, pul­mo­nary edema, nasal congestion, and allergic rhinitis. Less common symp­toms were hypo­­tension, headache, rash, urticaria, pruritus, nausea, vomiting, and chills.

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 for life-threatening (Grade 4) reac­tions. 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 the first and second day after all in­fusions. Patients with a history of obstructive pul­mo­nary disorders may require addi­tion­al post-infusion medications to man­age res­pira­tory com­pli­ca­tions. Consider pre­scrib­ing short- and long-acting bron­cho­di­lators and inhaled corticosteroids for patients with obstructive pul­mo­nary disorders.

Interference with Serological Testing - Dara­tu­mu­mab binds to CD38 on red blood cells (RBCs) and results in a pos­i­tive Indirect Antiglobulin Test (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®.

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%) were: in­fusion reac­tions (48%), fatigue (39%), nausea (27%), back pain (23%), pyrexia (21%), cough (21%), and upper res­pira­tory tract in­fec­tion (20%).

Serious adverse reac­tions were reported in 51 (33%) patients. The most frequent serious adverse reac­tions were pneu­monia (6%), general physical health deterioration (3%), and pyrexia (3%).

DRUG INTERACTIONS - No drug inter­action studies have been per­formed

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. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal.

Cautions Concerning Forward-Looking Statements

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing prod­uct develop­ment and the poten­tial benefits of 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 Research & Development, LLC 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; com­pe­ti­tion, in­­clud­ing techno­logical ad­vances, new prod­ucts and patents attained by com­pet­i­tors; chal­lenges to patents; manu­facturing dif­fi­culties and delays; 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 description 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.

References:

1. The U.S. Food and Drug Administration. "Expedited Programs for Serious Conditions." Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM358301.pdf. Accessed July 2016.
2. American Cancer Society. "Multiple Myeloma Overview." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed July 2016.
3. Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
4. DARZALEX Prescribing Information, November 2015.
5. Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immuno­pheno­typic analysis of 306 cases of multiple myeloma. Am J Clin Pathol. 2004;121:482–488. doi: 10.1309/74R4TB90BUWH27JX.
6. Krejcik, J. et al. Immunomodulatory Effects and Adaptive Immune Response to Daratumumab in Multiple Myeloma. Available at: https://ash.confex.com/ash/2015/webprogram/Paper79122.html. Accessed July 2016.
7. American Cancer Society. "Multiple Myeloma Overview." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed July 2016.
8. Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
9. National Cancer Institute. "NCI Dictionary of Cancer Terms: Refractory." Available at: http://www.cancer.gov/publications/dictionaries/cancer-terms?expand=R. Accessed July 2016.
10. Richardson, et al. "The Treatment of Relapsed and Refractory Multiple Myeloma." ASH Education Book January 1, 2007 vol. 2007 no. 1 317-323.
11. Becker N. Epidemiology of multiple myeloma. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 2011;183:25-35.
12. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of New Cancers in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=0&window=1&submit=%C2%A0Execute. Accessed July 2016.
13. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide: Number of Cancer Deaths in 2015. Available at: http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=17270&Text-c=Multiple+myeloma&pYear=3&type=1&window=1&submit=%C2%A0Execute. Accessed July 2016.
14. American Cancer Society. "How is Multiple Myeloma Diagnosed?" Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed July 2016.

Source: Janssen.