Data Published in The New England Journal of Medicine Show Single-Agent Daratumumab Demonstrated a 36 Percent Overall Response Rate and Tolerable Safety Profile in Heavily Pre-Treated Multiple Myeloma Patients

RARITAN, N.J., Aug. 26, 2015 /PRNewswire/ -- Janssen Research & Development, LLC announced today data from the multicenter, two-part, open-label Phase 1/2 GEN501 study published in The New England Journal of Medicine show daratumumab, an investigational, human anti-CD38 monoclonal antibody, demonstrated a tolerable safety profile as a monotherapy in patients with multiple myeloma who had relapsed after or were refractory (resistant) to at least two or more prior lines of therapy, including proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), chemotherapy and autologous stem cell transplantation. Daratumumab also demonstrated a 36 percent overall response rate (ORR) in patients treated with a 16 mg/kg dose, with responses improving (or "deepening") over time. Patients enrolled in the study had a median of four prior lines of therapy and 64 percent were refractory to both PIs and IMiDs.

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 are refractory to both PIs and IMiDs have a poor prognosis, with an estimated median overall survival of nine months.²

"What is impressive about this study is that daratumumab monotherapy induced durable responses that improved, or deepened, over time and 65 percent of responding patients remained in remission at 12 months," said lead author Henk M. Lokhorst, M.D., Ph.D., Department of Haematology, VU University Medical Center, Amsterdam, Netherlands. "These findings speak to the potential of daratumumab as an option for patients with multiple myeloma who no longer respond to existing therapies."

The GEN501 trial had a two-part study design. In Part 1, 32 patients were treated with escalating doses and no maximum tolerated dose was identified. In Part 2, 72 patients were enrolled in a dose expansion cohort and received either 8 mg/kg (30 patients) or 16 mg/kg (42 patients) of daratumumab at various schedules until disease progression or unmanageable toxicity to optimize doses identified in Part 1. Following this study, 16 mg/kg was chosen as the dose to be used in all daratumumab clinical trials.

Patients had a median of four prior lines of therapy and 79 percent were refractory to their last therapy, including both lenalidomide and bortezomib (64 percent). Additionally, 76 percent of patients previously received an autologous stem cell transplant. The primary endpoint for this trial was safety. Secondary endpoints were pharmacokinetics, objective response according to the International Myeloma Working Group (IMWG) uniform response criteria for myeloma, relative reductions in the levels of M protein and free light chains, time to disease progression, duration of response, progression-free survival and overall survival.

In the 16 mg/kg cohort, the ORR was 36 percent (11 partial responses, two very good partial responses and two complete responses) and 10 percent in the 8 mg/kg cohort (three partial responses). The two complete responses were confirmed with the use of a novel assay. Median progression-free survival was 5.6 months (95% CI: 4.2, 8.1) and 65 percent (95% CI: 28, 86) of responders remained in remission at 12 months.

"These data were part of our recent submission package to the FDA for daratumumab. Our hope is that daratumumab will offer a new treatment for patients with multiple myeloma who are greatly in need of new options," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen. "We are confident in our comprehensive development plan for daratumumab, which includes studying the medicine in earlier lines of therapy, both as a single agent and in combination with existing therapies."

In the 16 mg/kg cohort, serious adverse events (AEs) occurred in 33 percent of patients. Infusion-related reactions (IRRs) occurred in 71 percent of patients in both the 8 mg/kg and 16 mg/kg cohorts, and all were grades 1 and 2, except for the occurrence of grade 3 reactions in one patient. The majority of IRRs occurred during the first infusion, with notably fewer during subsequent infusions. No patient discontinued treatment due to an IRR. The most common AEs in either treatment group were fatigue, allergic rhinitis and pyrexia (fever). The most frequent hematologic AE was neutropenia (abnormally low levels of neutrophils, a type of white blood cell), which occurred in 12 percent of patients (n=5) in the 16 mg/kg cohort. Grade 3 or 4 AEs were reported in 26 percent of patients in the 16 mg/kg cohort, with pneumonia (n=5) and thrombocytopenia (abnormally low levels of platelets in the blood; n=4) as the most common in both the 8 mg/kg and 16 mg/kg cohorts.

On July 9, 2015, Janssen completed the rolling submission of its Biologic License Application (BLA) for daratumumab to 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 IMiD, or who are double refractory to a PI and an IMiD. Daratumumab received Breakthrough Therapy Designation from the FDA for this patient population in May 2013. The regulatory submission for daratumumab will be primarily supported by data from the Phase 2 MMY2002 (SIRIUS) monotherapy study presented in May/June 2015 at the 51^st Annual Meeting of the American Society of Clinical Oncology (ASCO), along with additional data from four other studies, including GEN501.

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 daratumumab. If approved, daratumumab would be commercialized in the U.S. by Janssen Biotech, Inc.

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., behind 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 124,225 people will be diagnosed and 87,084 will die from the disease in 2015.^5,6 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.⁷ Patients who relapse after treatment with standard therapies, including PIs or IMiDs, have poor prognoses and few treatment options.²

About Daratumumab
Daratumumab is an investigational human monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. It is believed to induce rapid tumor cell death through multiple immune-mediated mechanisms,⁸ including complement-dependent cytotoxicity,⁸ antibody-dependent cellular phagocytosis⁹ and antibody-dependent cellular cytotoxicity,⁸ as well as via induction of apoptosis.¹⁰ 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 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 www.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.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed August 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 August 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 August 2015.
⁵ 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 August 2015.
⁶ 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 August 2015.
⁷ American Cancer Society. "How is Multiple Myeloma Diagnosed?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-diagnosis. Accessed August 2015.
⁸ Michael 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 Yulian Khagi and Tomer M Mark. Potential role of daratumumab in the treatment of multiple myeloma. Onco Targets Ther. 2014; 7: 1095–1100.
¹⁰ Jing Yang and Qing Yi. Therapeutic monoclonal antibodies for multiple myeloma: an update and future perspectives. Am J Blood Res. 2011; 1(1): 22–33.

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