Data Show Daratumumab Achieved a Pronounced Overall Response Rate as a Single-Agent with Tolerable Safety Profile in Heavily Pre-Treated Multiple Myeloma Patients

CHICAGO and RARITAN, N.J., May 30, 2015 /PRNewswire/ -- Data from the international, multi-center, open-label, two-part, single-arm Phase 2 MMY2002 (SIRIUS) trial show treatment with single-agent daratumumab – an investigational, human anti-CD38 monoclonal antibody – achieved an overall response rate (ORR) of 29.2 percent (95% CI, 20.8-38.9), as assessed by an independent review committee, in heavily pre-treated patients with multiple myeloma. The ORR was consistent among the pre-specified subgroups based on age, prior lines of therapy, type of myeloma and baseline renal function. Median duration of response was 7.4 months (95% CI, 5.5-not estimable). Ninety-five percent of patients in the study were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Patients received a median of five prior lines of therapy, including a PI and an IMiD. No patients discontinued treatment due to infusion-related reactions (IRRs) and 4.7 percent of patients discontinued treatment due to adverse events (AEs), none of which were considered drug-related.

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by excess growth and survival of malignant plasma cells.[1] Patients who relapse after treatment with standard therapies, including PIs or IMiDs, have poor prognoses and few treatment options.[2]  

Janssen Research & Development, LLC (Janssen) announced the data, which will be included today during the official press program at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL. These data will be presented in full during the myeloma oral abstract session on Tuesday, June 2^nd at 11:21 a.m. Central Time (CT) by lead 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 is particularly noteworthy to see this level of response with a single-agent in this heavily pre-treated population. Ninety-seven percent of patients in this study were refractory to their last line of therapy and 95 percent were double refractory to both a PI and an IMiD," said Dr. Lonial. "These findings speak to the potential of daratumumab as an effective and tolerable option for people with multiple myeloma who have exhausted other available treatment options."

In part one of this ongoing international, multi-center, open-label, two-part, single-arm study, 34 patients were randomized to receive either 8 mg/kg of daratumumab once every four weeks (Q4W) or 16mg/kg once a week (QW) for eight weeks, then once every two weeks (Q2W) for 16 weeks and once every four weeks (Q4W) following, until disease progression or unacceptable toxicity. In part two, 90 additional patients were enrolled to receive 16 mg/kg of daratumumab on the same dosing schedule as in part one. Results are reported for all patients in parts one and two treated with 16 mg/kg of daratumumab (n=106). Very good partial response (VGPR) or better was achieved in 12 percent (95% CI, 7-20) of patients, with three stringent complete responses (sCR) (95% CI, 0.6-8.0) and 10 very good partial responses (VGPR) (95% CI, 4.6-16.7) reported. Median overall survival (OS) has not been reached, and the estimated one-year overall survival rate is 65 percent. The median progression-free survival was 3.7 months. After a median follow up of 9.4 months, 45.2 percent of responders remain on therapy.

"We have a broad portfolio of blood cancer treatments, and we're particularly proud of our work globally in multiple myeloma," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. "We have been working diligently to develop medicines with new mechanisms of action, such as daratumumab, and we will continue to study the compound as both a single-agent and in combination with backbone therapies to identify all settings where it may be effective."

Serious AEs occurred in 30 percent of patients. The most common AEs were fatigue (39.6 percent), anemia (33 percent), nausea (29.2 percent), thrombocytopenia (25.5 percent), neutropenia (22.6 percent), back pain (22.6 percent) and cough (20.8 percent). Five patients (4.7 percent) discontinued treatment due to AEs, none of which were considered drug-related. Infusion-related reactions (IRR) were reported in 42.5 percent of patients and were predominantly grade 1 or 2 (4.7 percent grade 3; no grade 4 reported). These occurred mainly during the first infusion. The most common IRRs included nasal congestion (12 percent), throat irritation (7 percent), cough, dyspnea, chills and vomiting (6 percent each) – all of which were treated with standard of care and slower infusion rates.

On May 1, 2013, Janssen received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for daratumumab for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a PI and an IMiD – the current standards of care – or who are double refractory to a PI and an IMiD. On May 20, 2015, Janssen announced plans to submit a Biologics License Application (BLA) to the FDA and European Medicines Agency (EMA) for daratumumab this year, based on these MMY2002 data.

As part of the Janssen commitment to help patients in need, the Company also plans to initiate an expanded access program (EAP) for daratumumab for eligible patients in the United States (U.S.) living with multiple myeloma who are double refractory to a PI and an IMiD and/or have received three or more prior lines of therapy, including a PI and an IMiD. EAPs provide a way to make investigational medicines still in the pre-approval period available to patients whose serious or life-threatening illnesses are not helped by currently available treatment options. Further details about the program will be available on www.clinicaltrials.gov in the near future.

In August 2012, Janssen Biotech, Inc. and Genmab entered an agreement which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. Janssen is currently the sponsor of all but one study globally.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.[1] Multiple myeloma is the third most common blood cancer in the U.S., following only leukemia and lymphoma.[3] 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.[4] Globally, it is estimated that 114,251 people will be diagnosed and 80,019 will die from the disease.[5] 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.[6]

About Daratumumab
Daratumumab is an investigational human IgG₁k monoclonal antibody (mAb) that binds with high affinity to the transmembrane ectoenzyme, CD38, on the surface of multiple myeloma cells. It induces rapid tumor cell death through diverse mechanisms of action. Five Phase 3 clinical studies with daratumumab in relapsed and frontline settings are currently ongoing. Additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma.

About Janssen Research & Development, LLC 
At Janssen, we are dedicated to addressing and solving some of the most important unmet medical needs of our time in oncology, immunology, neuroscience, infectious diseases and vaccines, and cardiovascular and metabolic diseases. Driven by our commitment to patients, we develop innovative products, services and healthcare solutions to help people throughout the world. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson. Please visit http://www.janssenrnd.com for more information.

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 http://oncology.janssenrnd.com. 

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. 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 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.

[1] American Cancer Society. "Multiple Myeloma Overview" http://www.cancer.net/cancer-types/multiple-myeloma/overview. Accessed May 2015.

[2] Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.

[3] National Cancer Institute. "A Snapshot of Myeloma." Available at www.cancer.gov/research/progress/snapshots/myeloma. Accessed May 2015.

[4] American Cancer Society. "What are the key statistics about multiple myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-key-statistics. Accessed May 2015.

[5] GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide. Available at http://globocan.iarc.fr/Pages/fact_sheets_population.aspx. Accessed May 2015.

[6] American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed May 2015.

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