Janssen Announces Clinical Trial Collaboration and Supply Agreement with Amgen to Evaluate daratumumab (DARZALEX®) in Combination with carfilzomib (KYPROLIS®)

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Nov 10, 2016, 08:34 ET

HORSHAM, Pa., Nov. 10, 2016 /PRNewswire/ -- Janssen Biotech, Inc. today announced that the company has entered into a master clinical trial collaboration and supply agreement with Onyx Pharmaceuticals, Inc., a wholly-owned subsidiary of Amgen, Inc., to evaluate the efficacy and safety of the first-in-class CD38-directed immunotherapy daratumumab (DARZALEX^®) in combination with a proteasome inhibitor (PI) carfilzomib (KYPROLIS^®) and dexamethasone. The agreement covers all potential opportunities for combining daratumumab and carfilzomib for the treatment of patients with cancer. Janssen licensed daratumumab from Genmab A/S and is responsible for all global development, marketing and manufacturing.¹ Carfilzomib is developed and commercialized by Amgen.

The first study under this collaboration agreement will focus on a Phase 3, randomized, open-label, registration study to determine if daratumumab in combination with carfilzomib (56 mg/m² twice weekly) and dexamethasone improves progression-free survival (PFS), compared to carfilzomib and dexamethasone alone, in patients with multiple myeloma who have received one to three prior therapies. The study is anticipated to start dosing patients in 2017. Under the terms of the agreement, the trial will be sponsored by Amgen. Financial terms have not been disclosed.

As part of an earlier collaboration agreement, a separate, ongoing study is evaluating the safety and pharmacokinetics of this combination regimen, in addition to a second regimen of daratumumab in combination with carfilzomib (70 mg once weekly), lenalidomide and dexamethasone in newly diagnosed patients with multiple myeloma.

This research will build on clinical findings from the Phase 3 POLLUX and CASTOR clinical studies evaluating daratumumab in combination with lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively, in patients with multiple myeloma who have received at least one prior therapy. Findings from the POLLUX trial were published in The New England Journal of Medicine, with an accompanying editorial, in October 2016, and findings from the CASTOR trial were published in The New England Journal of Medicine in August 2016.

"We are delighted to partner with Amgen to continue to explore the potential role of daratumumab in combination with novel treatment regimens, especially now that we have results from the Phase 3 POLLUX and CASTOR studies," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. "This collaboration reflects our shared vision to better meet the needs of patients with multiple myeloma who are still in need of new therapeutic options."

DARZALEX is the first CD38-directed monoclonal antibody (mAb) approved to treat patients with multiple myeloma. It was first approved by the FDA in November 2015 as a treatment for 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 immunomodulatory agent.² 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.³DARZALEX is also approved in Europe and Canada for a similar patient population.

KYPROLIS is a PI approved in the U.S. and Canada as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy and in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.

In August 2016, Janssen submitted a supplemental Biologics License Application (sBLA) to the FDA for daratumumab in combination with lenalidomide (an immunomodulatory agent) and dexamethasone, or bortezomib (a PI) and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy.⁴ Daratumumab received Breakthrough Therapy Designation from the FDA for this indication in July 2016.⁵

DARZALEX is commercialized in the U.S. by Janssen Biotech, Inc. For more information, visit www.DARZALEX.com.

About DARZALEX^® (daratumumab) Injection, for Intravenous Infusion
DARZALEX^® (daratumumab) injection for intravenous use is the first CD38-directed monoclonal antibody (mAb) approved anywhere in the world.³ CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of disease stage.⁶ 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.³Daratumumab also demonstrates other effects on the immune system, including lysis of immunosuppressive CD38+ regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs).³ 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 for a solid tumor indication and in other malignant and pre-malignant diseases in which CD38 is expressed, such as smoldering myeloma and non-Hodgkin's lymphoma. DARZALEX was the first mAb to receive regulatory approval to treat relapsed or refractory multiple myeloma.³

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.¹¹Globally, it is estimated that 124,225 people were diagnosed, and 87,084 died from the disease in 2015.¹²While 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. Patients who relapse after treatment with standard therapies (including PIs or immunomodulatory agents) typically have poor prognoses and few remaining options.⁸

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, including planned clinical trials under a new collaboration agreement. 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., Janssen Research & Development, LLC and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: the potential that the expected benefits and opportunities related to the collaboration may not be realized or may take longer to realize than expected; challenges inherent in product research and development, including the uncertainty of clinical success and obtaining regulatory approvals; uncertainty of commercial success for new products or new indications; 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 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.

¹ Janssen Biotech, Inc. "Janssen Biotech Announces Global License and Development Agreement
for Investigational Anti-Cancer Agent Daratumumab." Issued August 30, 2012.
² 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.
³ DARZALEX Prescribing Information, November 2015.
⁴ Janssen Biotech, Inc. "Janssen Submits Application to U.S. FDA to Expand Indication for Daratumumab (DARZALEX^®)." Issued August 17, 2016.⁵ Janssen Research & Development, LLC. "Daratumumab (DARZALEX^®) Granted Breakthrough Therapy Designation by U.S. Food and Drug Administration (FDA) for Use in Combination with Standard of Care Regimens for Patients with Multiple Myeloma." Issued July 25, 2016.
⁶ 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
⁷ American Cancer Society. "Multiple Myeloma Overview." Available at: http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma. Accessed November 2015.
⁸ Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.
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¹¹ National Cancer Institute. "NCI Dictionary of Cancer Terms: Relapsed." Available at: http://www.cancer.gov/publications/dictionaries/cancer-terms?expand=R. Accessed November 2015.
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 August 2016.