Horsham, PA (Press Release) – 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.³ DARZALEX 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.³ Dara­tu­mu­mab 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.¹¹ Globally, it is esti­mated that 124,225 people were diag­nosed, and 87,084 died from the disease in 2015.¹² 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. 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.

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Source: Janssen Biotech, Inc.