Supplemental Biologics License Application (sBLA) seeks first indi­ca­tion for DARZALEX for the treat­ment of newly diag­nosed patients

Raritan, NJ (Press Release) – Janssen Biotech, Inc. today announced that it has submitted a supple­mental Biologics License Application (sBLA) to the U.S. Food and Drug Admin­istra­tion (FDA) for DARZALEX® (dara­tu­mu­mab). This appli­ca­tion seeks to expand the current indi­ca­tion, using DARZALEX in com­bi­na­tion with bor­tez­o­mib (a pro­te­a­some inhibitor [PI]), mel­phalan and pred­ni­sone, for the treat­ment of patients with newly diag­nosed multiple myeloma who are in­eli­gible for au­tol­o­gous stem cell trans­planta­tion (ASCT). If approved, this would be the fifth indi­ca­tion for DARZALEX in the U.S. and its first in the frontline setting.

"The addi­tion of DARZALEX to this treat­ment regi­men provides a sub­stan­tial, clin­i­cally meaningful impact on prolonging remission for newly diag­nosed patients with multiple myeloma," said Mark Wildgust, Vice Pres­i­dent, Global Medical Affairs, Janssen Oncology. "Today's sub­mission builds upon the con­sis­tent clin­i­cal benefit of DARZALEX in com­bi­na­tion with standard of care regi­mens and is an exciting step for­ward for patients and physicians."

As part of the appli­ca­tion, Janssen has requested Priority Review, which the FDA grants to investi­ga­tional ther­a­pies that, if approved, may offer sig­nif­i­cant im­prove­ments in the treat­ment, prevention or diag­nosis of a serious con­di­tion.¹ The FDA will inform Janssen whether Priority Review has been granted within the next 60 days.

The regu­la­tory sub­mission is based on data from the Phase 3 ALCYONE (MMY3007) study of DARZALEX in com­bi­na­tion with bor­tez­o­mib, mel­phalan and pred­ni­sone in frontline multiple myeloma. Data from the ALCYONE study were accepted as a late-breaking abstract (#LBA-4) at the 59th Annual Meeting of the American Society of Hematology. These data were also used as the basis for a regu­la­tory sub­mission to the European Medicines Agency (EMA) announced today.

DARZALEX was first approved by the FDA in November 2015 as a mono­therapy 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 an immuno­modu­latory agent.² It received addi­tional approvals in November 2016 in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, or bor­tez­o­mib and dexa­metha­sone, for the treat­ment of patients with multiple myeloma who have received at least one prior ther­apy.³ In June 2017, DARZALEX was approved in com­bi­na­tion with poma­lido­mide and dexa­metha­sone for the treat­ment of patients with multiple myeloma who have received at least two prior ther­a­pies, in­­clud­ing lena­lido­mide and a PI.⁴

About DARZALEX® (dara­tu­mu­mab) Injection, for Intravenous Infusion

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous use is the first CD38-directed anti­body approved any­where in the world.⁵ CD38 is a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of disease stage.6 DARZALEX is believed to induce tumor cell death through multiple immune-mediated mech­a­nisms of action, in­­clud­ing complement-dependent cyto­toxicity (CDC), anti­body-dependent cell-mediated 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.⁵ A subset of myeloid derived sup­pressor cells (MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by DARZALEX.5 DARZALEX is being eval­u­ated in a com­pre­hen­sive clin­i­cal devel­op­ment pro­gram across a range of treat­ment settings in multiple myeloma, such as in frontline and re­lapsed settings.^{7,8,9,10,11,12,13,14} 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.^15,16,17 DARZALEX was the first CD38-directed anti­body to receive regu­la­tory approval to treat re­lapsed or refractory multiple myeloma.²

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow un­con­trol­lably in the bone marrow.^18,19 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.^20,21 Relapsed cancer means the disease has returned after a period of initial, partial or com­plete remission.²² It is esti­mated that 30,280 people will be diag­nosed and 12,590 will die from the disease in the United States in 2017.²³ 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.²⁴

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.

IMPORTANT SAFETY INFORMATION

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, hyper­tension, laryngeal edema and pul­mo­nary edema. Signs and symp­toms may in­clude res­pira­tory symp­toms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting and nausea. Less common symp­toms were wheezing, allergic rhinitis, pyrexia, chest dis­comfort, pruritus, and hypo­tension.

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 fol­low­ing DARZALEX in­fusions. Patients with a history of chronic obstructive pul­mo­nary disease may require addi­tional post-infusion medica­tions to man­age res­pira­tory compli­ca­tions. Consider pre­scrib­ing short- and long-acting broncho­dilators and inhaled cortico­steroids for patients with chronic obstructive pul­mo­nary disease.

Interference with Serological Testing - Dara­tu­mu­mab binds to CD38 on red blood cells (RBCs) and results in a pos­i­tive Indirect Antiglobulin Test (Indirect 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.

Neutropenia - DARZALEX may in­­crease neu­tro­penia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­­fac­­turer's pre­scrib­ing in­­for­ma­tion for back­ground ther­a­pies. Monitor patients with neu­tro­penia for signs of in­fec­tion. DARZALEX dose delay may be required to allow re­cov­ery of neu­tro­phils. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with growth factors.

Thrombocytopenia - DARZALEX may in­­crease thrombo­cytopenia induced by back­ground ther­apy. Monitor com­plete blood cell counts periodically during treat­ment according to manu­facturer's pre­scribing in­­for­ma­tion for back­ground ther­a­pies. DARZALEX dose delay may be required to allow re­cov­ery of platelets. No dose reduction of DARZALEX is rec­om­mended. Consider sup­port­ive care with trans­fusions.

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 – In patients who received DARZALEX in com­bi­na­tion with lena­lido­mide and dexa­metha­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: neu­tro­penia (92%), thrombo­cyto­penia (73%), upper res­pira­tory tract in­fec­tion (65%), in­fusion reac­tions (48%), diarrhea (43%), fatigue (35%), cough (30%), muscle spasms (26%), nausea (24%), dyspnea (21%) and pyrexia (20%). The over­all in­ci­dence of serious adverse reac­tions was 49%. Serious adverse reac­tions were pneu­monia (12%), upper res­pira­tory tract in­fec­tion (7%), influenza (3%) and pyrexia (3%).

In patients who received DARZALEX in com­bi­na­tion with bor­tez­o­mib and dexa­metha­sone, the most frequently reported adverse reac­tions (incidence ≥20%) were: thrombo­cyto­penia (90%), neu­tro­penia (58%), periph­eral sensory neu­rop­athy (47%), in­fusion reac­tions (45%), upper res­pira­tory tract in­fec­tion (44%), diarrhea (32%), cough (27%), periph­eral edema (22%), and dyspnea (21%). The over­all in­ci­dence of serious adverse reac­tions was 42%. Serious adverse reac­tions were upper res­pira­tory tract in­fec­tion (5%), diarrhea (2%) and atrial fibrillation (2%).

In patients who received DARZALEX as mono­therapy, the most frequently reported adverse reac­tions (incidence ≥20%) were: neu­tro­penia (60%), thrombo­cytopenia (48%), 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%).

In patients who received DARZALEX in com­bi­na­tion with poma­lido­mide and dexa­metha­sone, the most frequent adverse reac­tions (>20%) were in­fusion reac­tions (50%), diarrhea (38%), con­sti­pa­tion (33%), nausea (30%), vomiting (21%), fatigue (50%), pyrexia (25%), upper res­pira­tory tract in­fec­tion (50%), muscle spasms (26%), back pain (25%), arthralgia (22%), dizzi­ness (21%), insomnia (23%), cough (43%) and dyspnea (33%). The over­all in­ci­dence of serious adverse reac­tions was 49%. Serious adverse reac­tions reported in ≥5% patients in­cluded pneu­monia (7%).

DRUG INTERACTIONS

Effect of Other Drugs on dara­tu­mu­mab: The coadministration of lena­lido­mide, poma­lido­mide or bor­tez­o­mib with DARZALEX did not affect the phar­ma­co­ki­netics of dara­tu­mu­mab.

Effect of Dara­tu­mu­mab on Other Drugs: The coadministration of DARZALEX with bor­tez­o­mib did not affect the phar­ma­co­ki­netics of bor­tez­o­mib.

This press release con­tains "forward-looking state­ments" as defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing the benefits and timing of the poten­tial approval of a new indi­ca­tion for DARZALEX® (dara­tu­mu­mab) and further devel­op­ment of DARZALEX. 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., any of the other Janssen Pharma­ceutical Com­panies and/or Johnson & Johnson. Risks and un­cer­tain­ties in­clude, but are not limited to: chal­lenges in­her­ent in prod­uct research and develop­ment, in­­clud­ing the un­certainty of clin­i­cal success and obtaining regu­latory approvals; uncertainty of commercial success for new indi­ca­tions; manu­facturing dif­fi­culties or delays; com­pe­ti­tion, in­­clud­ing tech­no­logical ad­vances, new prod­ucts and patents attained by competi­tors; chal­lenges to patents; prod­uct efficacy or safety con­cerns resulting in prod­uct recalls or regu­la­tory action; 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 1, 2017, in­­clud­ing under "Item 1A. Risk Factors," its most recently filed Quarterly Report on Form 10-Q, in­­clud­ing under the caption "Cautionary Note Regarding Forward-Looking State­ments," 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. Neither the Janssen Pharma­ceutical Com­panies nor 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.