First-in-class immuno­therapy approved for multiple myeloma patients who have received three or more prior lines of ther­apy, in­­clud­ing a pro­te­a­some inhibitor (PI) and an immuno­modu­la­tory agent or who are double refractory to a PI and immuno­modu­la­tory agent

Horsham, PA (Press Release) – Janssen Biotech, Inc., a Janssen Pharma­ceu­tical Company of Johnson & Johnson, announced today the U.S. Food and Drug Admin­istra­tion (FDA) has approved DARZALEX^® (dara­tu­mu­mab) injection for in­tra­venous in­fusion for the treat­ment of 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.¹ 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 con­firmatory trials. Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^2,3 Refractory cancer occurs when a patient's disease is resistant to treat­ment or in the case of multiple myeloma, the disease progresses within 60 days of their last ther­apy.^4,5 Relapsed cancer means the disease has returned after a period of initial, partial or com­plete remission.⁶

DARZALEX is the first human anti-CD38 mono­clonal anti­body (mAb) approved any­where in the world. CD38 is a surface protein that is ex­pressed by most, if not all, multiple myeloma cells.⁷ DARZALEX is believed to induce tumor cell death through multiple immune-mediated mech­a­nisms of action,^8,9 in addi­tion to apopto­sis, in which a series of molecular steps in a cell lead to its death.¹⁰ Its approval comes just two months after the Biologics License Application (BLA) was accepted for Priority Review by the FDA in September 2015.¹¹ DARZALEX received Break­through Therapy Desig­na­tion from the FDA for this indi­ca­tion in May 2013.¹²

“Multiple myeloma is a highly complex disease and remains incurable, with almost all patients relapsing or becoming resistant to ther­apy,” said DARZALEX clin­i­cal trial investigator Paul G. Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute. “With DARZALEX, we have a promising new immuno­therapy, which has shown pronounced efficacy as a single agent with an acceptable adverse event profile. This is especially im­por­tant for treating these heavily pre-treated patients in whom all of the major classes of cur­rently avail­able med­i­cines have failed.”

The pivotal open-label Phase 2 MMY2002 (SIRIUS) study showed treat­ment with single-agent DARZALEX resulted in an over­all response rate (ORR) of 29.2 per­cent (95% CI; 20.8, 38.9) in patients who received a median of five prior lines of ther­apy, in­­clud­ing a PI and an immuno­modu­la­tory agent.¹

Stringent com­plete response (sCR) was reported in 2.8 per­cent of patients, very good partial response (VGPR) was reported in 9.4 per­cent of patients, and partial response (PR) was reported in 17 per­cent of patients.¹ These efficacy results were based on ORR as de­ter­mined by the Independent Review Committee assess­ment using IMWG (International Myeloma Work­ing Group) criteria and the range for median duration of response.

For responders, the median duration of response was 7.4 months (range 1.2-13.1+ months).¹ At base­line, 97 per­cent of patients were refractory to their last line of ther­apy, 95 per­cent were refractory to both a PI and an immuno­modu­la­tory agent, and 77 per­cent were refractory to alkylating agents.¹ Additional efficacy data from the Phase 1/2 GEN501 mono­therapy study – published in The New England Journal of Medicine in August 2015 – also sup­port this approval.¹

“The responses we saw in clin­i­cal trials that led to today’s approval were striking, especially con­sidering that these patients received a median of five prior lines of ther­apy,” said MMY2002 investigator Sagar Lonial, M.D., Chief Medical Officer, Winship Cancer Institute of Emory University and Pro­fessor and Executive Vice Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine. “It appears the mech­a­nism of action for dara­tu­mu­mab (DARZALEX) may play an im­por­tant role in its single-agent activity among this group of ad­vanced-stage multiple myeloma patients.”

“Living with multiple myeloma is chal­leng­ing, both physically and emotionally, especially as the disease progresses and treat­ment options be­come more limited,” said Debby Graff, a patient enrolled in a clin­i­cal trial at Dana-Farber Cancer Institute. “I am en­cour­aged by emerging treat­ments for multiple myeloma, and I have a new outlook on my path for­ward.”

“While there have been con­siderable im­prove­ments over the past decade in the treat­ment of people living with multiple myeloma, these patients face a long, hard road – especially those whose disease has re­lapsed or is no longer responding to current ther­a­pies,” said Walter M. Capone, Pres­i­dent and Chief Executive Officer of the Multiple Myeloma Research Foundation (MMRF). “With the approval of dara­tu­mu­mab, a new anti­body option targeting CD38, along with ongoing work to ad­vance the devel­op­ment of novel classes of ther­a­pies by both Janssen and MMRF, we are ushering in a new era of myeloma ther­apy focused on individualized treat­ment ap­proaches for patients with sig­nif­i­cant unmet needs.”

“Our focus is devel­op­ing transformational med­i­cines for people living with hard-to-treat cancers, such as multiple myeloma,” said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. “The rapid devel­op­ment and approval of DARZALEX – the first human anti-CD38 mono­clonal anti­body – is a great example of this commitment and our ongoing work in devel­op­ing immuno­therapies. We will con­tinue to study this com­­pound as both a mono- and a com­bi­na­tion ther­apy to under­stand its full clin­i­cal benefit for patients across the treat­ment con­tin­uum in multiple myeloma and other tumor types.”

The warnings and precautions for DARZALEX in­clude in­fusion reac­tions, inter­fer­ence with serological testing and inter­fer­ence with deter­mi­na­tion of com­plete response (see Important Safety Information).¹ The most frequently reported adverse reac­tions (incidence ≥20%) were: fatigue, nausea, back pain, pyrexia, cough and upper res­pira­tory tract in­fec­tion.¹

In data from three pooled clin­i­cal studies in­­clud­ing a total of 156 patients, four per­cent of patients dis­con­tinued treat­ment due to adverse reac­tions.1 Infusion reac­tions were reported in approx­i­mately half of all patients treated with DARZALEX.¹ Common (≥5 per­cent) symp­toms of in­fusion reac­tions in­cluded nasal congestion, chills, cough, allergic rhinitis, throat irritation, dyspnea (shortness of breath) and nausea.¹ Severe in­fusion reac­tions, in­­clud­ing bron­cho­spasm, dyspnea, hypoxia and hyper­tension (<2 per­cent each).¹

The rec­om­mended dose of DARZALEX is 16 mg/kg body weight admin­istered as an in­tra­venous in­fusion.¹ The dosing schedule begins with weekly admin­istra­tion (weeks 1-8) and reduces in frequency over time to every two weeks (weeks 9-24) and ultimately every four weeks (week 25 onwards until disease pro­gres­sion).¹

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.¹³ Janssen is cur­rently the global sponsor of all but one clin­i­cal study. DARZALEX will be com­mer­cial­ized in the U.S. by Janssen Biotech, Inc.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^2,3 Multiple myeloma is the third most common blood cancer in the U.S., fol­low­ing only leukemia and lym­phoma.¹⁴ Approximately 26,850 new patients will be diag­nosed with multiple myeloma, and approx­i­mately 11,240 people will die from the disease in the U.S. in 2015.¹⁵ Globally, it is esti­mated that 124,225 people will be diag­nosed, and 87,084 will die from the disease in 2015.^16,17 While some patients with multiple myeloma have no symp­toms at all, most patients are diag­nosed due to symp­toms which can in­clude bone problems, low blood counts, cal­cium elevation, kidney problems or in­fec­tions.¹⁸ Patients who relapse after treat­ment with standard ther­a­pies (including PIs or immuno­modu­la­tory agents) typically have poor prognoses and few remaining options.³

Access to DARZALEX® (dara­tu­mu­mab) Injection, for Intravenous Infusion

DARZALEX (dara­tu­mu­mab) injection for in­tra­venous in­fusion will be avail­able for distribution in the U.S. within two weeks fol­low­ing FDA approval. Janssen Biotech offers com­pre­hen­sive access and sup­port in­­for­ma­tion, resources and services to assist U.S. patients in gaining access to DARZALEX through the Janssen CarePath Program. For more in­­for­ma­tion, health care providers or patients can contact: 1-844-55DARZA (1-844-553-2792). Information will also be avail­able at www.DARZALEX.com. Dedicated case coordinators are avail­able to work with both health­care providers and patients.

Patients with private or commercial insurance may be eli­gible for the Janssen CarePath Savings Program for DARZALEX. Information on the enrollment process will be avail­able online at www.CarePathSavingsProgram.com/DARZALEX.

About DARZALEX^® (dara­tu­mu­mab) Injection, for Intravenous Infusion

DARZALEX^® (dara­tu­mu­mab) injection for in­tra­venous in­fusion is indicated for the treat­ment of 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.¹ 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 con­firmatory trials. DARZALEX is the first human anti-CD38 mono­clonal anti­body (mAb) to receive U.S. Food and Drug Admin­istra­tion (FDA) approval to treat multiple myeloma. DARZALEX is believed to induce tumor cell death through apop­tosis, in which a series of molecular steps in a cell lead to its death^1,10 and multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­tox­icity (CDC), anti­body-dependent cellular cyto­tox­icity (ADCC) and anti­body-dependent cellular phago­cytosis (ADCP).^1,8 More in­­for­ma­tion will be avail­able at www.DARZALEX.com.

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: fatigue, nausea, back pain, pyrexia, cough, and upper res­pira­tory tract in­fec­tion.

Serious adverse reac­tions were reported in 51 (33%) of 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 Janssen Biotech, Inc.

Janssen Biotech, Inc. redefines the standard of care in immunology, on­col­ogy, urology and nephrology. Built upon a rich legacy of inno­va­tive firsts, Janssen Biotech has delivered on the promise of new treat­ments and ways to im­prove the health of individuals with serious disease. Beyond its inno­va­tive med­i­cines, Janssen Biotech is at the forefront of devel­op­ing education and public policy ini­tia­tives to ensure patients and their families, care­givers, advocates and health care professionals have access to the latest treat­ment in­­for­ma­tion, sup­port services and quality care. For more in­­for­ma­tion on Janssen Biotech, Inc. or its prod­ucts, visit www.janssenbiotech.com. Follow us on Twitter at www.twitter.com/JanssenUS.

Janssen in Oncology

In on­col­ogy, our goal is to fundamentally alter the way cancer is under­stood, diag­nosed and man­aged, reinforcing our commitment to the patients who in­spire us. In looking to find inno­va­tive ways to address the cancer chal­lenge, our pri­mary efforts focus on several treat­ment and prevention solu­tions. These in­clude a focus on hema­to­logic malig­nan­cies, prostate cancer and lung cancer; cancer interception with the goal of devel­op­ing prod­ucts that interrupt the carcinogenic process; bio­­markers that may help guide targeted, individualized use of our ther­a­pies; as well as safe and effective identi­fi­ca­tion and treat­ment of early changes in the tumor microenvironment. Please visit on­col­ogy.janssenrnd.com.

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing prod­uct devel­op­ment. 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 Biotech, Inc. and/or Johnson & Johnson. Risks and un­cer­tain­ties in­clude, but are not limited to: chal­lenges and un­cer­tain­ties in­her­ent in new prod­uct devel­op­ment, in­­clud­ing the uncertainty of clin­i­cal success and of obtaining regu­la­tory approvals; com­pe­ti­tion, in­­clud­ing technological ad­vances, new prod­ucts and patents attained by com­pet­i­tors; chal­lenges to patents; 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 December 28, 2014, 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. DARZALEX Prescribing Information, November 2015.
2. American Cancer Society. "Multiple Myeloma Overview." http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed November 2015.
3. Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
4. National Cancer Institute. “NCI Dictionary of Cancer Terms: Refractory.” Available at http://www.cancer.gov/publications/dictionaries/cancer-terms?expand=R. Accessed November 2015.
5. Richardson, et al. “The Treatment of Relapsed and Refractory Multiple Myeloma.” ASH Education Book January 1, 2007 vol. 2007 no. 1 317-323.
6. National Cancer Institute. “NCI Dictionary of Cancer Terms: Relapsed.” Available at http://www.cancer.gov/publications/dictionaries/cancer-terms?expand=R. Accessed November 2015.
7. Fedele G et al. CD38 Ligation in Peripheral Blood Mononuclear Cells of Myeloma Patients Induces Release of Protumorigenic IL-6 and Impaired Secretion of IFNγ Cytokines and Proliferation. Mediators Inflamm. 2013;2013:564687.
8. Michel de Weers et al. Daratumumab, a Novel Therapeutic Human CD38 Monoclonal Antibody, Induces Killing of Multiple Myeloma and Other Hematological Tumors. The Journal of Immunology. February 1, 2011. Vol. 186, No. 3 1840-1848.
9. Overdijk et al. Phagocytosis Is A Mechanism of Action for Daratumumab. Available at https://ash.confex.com/ash/2012/webprogram/Paper51257.html. Accessed September 2015.
10. Jansen JH, et al. Blood. 2012; 120.2974.
11. Janssen Research & Development, LLC. “U.S. FDA Grants Priority Review to Janssen for Daratumumab as a Treatment for Multiple Myeloma.” Issued September 4, 2015.
12. Janssen Research & Development, LLC. “Daratumumab Receives Breakthrough Therapy Designation in Double Refractory Multiple Myeloma from U.S. Food and Drug Administration.” Issued May 1, 2013.
13. Janssen Biotech, Inc. “Janssen Biotech Announces Global License and Development Agreement for Investigational Anti-Cancer Agent Daratumumab.” Issued August 30, 2012.
14. National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed November 2015.
15. American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed November 2015.
16. 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 November 2015.
17. 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 November 2015.
18. American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed November 2015.

Source: Janssen Biotech