DARZALEX com­bi­na­tion ther­apy offers a new option for patients pre­vi­ously treated with two commonly used treat­ments (lena­lido­mide and a pro­te­a­some inhibitor)

Horsham, PA (Press Release) – Janssen Biotech, Inc. announced today that the U.S. Food and Drug Admin­istra­tion (FDA) has approved the immuno­therapy DARZALEX® (dara­tu­mu­mab) in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for the treat­ment of patients with multiple myeloma who have received at least two prior ther­a­pies in­­clud­ing lena­lido­mide (an immuno­modu­la­tory agent) and a pro­te­a­some inhibitor (PI).¹ Clinical trial results showed an over­all response rate (ORR) of 59.2 per­cent with DARZALEX in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone in these patients.¹

DARZALEX is the first CD38-directed anti­body approved any­where in the world.² It was first approved by the FDA in November 2015 as a mono­therapy 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 an immuno­modu­la­tory agent.³ 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.⁴ To date, approx­i­mately 16,000 patients have been treated with DARZALEX.⁵

"Despite tremendous progress, most patients with multiple myeloma continually relapse or be­come resistant to avail­able ther­a­pies, such as PIs and immuno­modu­la­tory agents. Therefore, these patients con­tinue to need new options," said Ajai Chari M.D., Asso­ci­ate Pro­fessor of Medicine, Multiple Myeloma Program and Asso­ci­ate Director of Clinical Research, Mount Sinai Hospital. "With today's approval of DARZALEX, we now have a promising new com­bi­na­tion ther­apy that in clin­i­cal trials dem­onstrated pronounced clin­i­cal benefit for patients who have re­lapsed on two of the most widely used treat­ments."

This new indi­ca­tion for DARZALEX is sup­ported by data from the Phase 1b EQUULEUS study, which showed that the com­bi­na­tion of DARZALEX with poma­lido­mide and dexa­meth­a­sone resulted in an ORR of 59.2 per­cent (95 per­cent CI: 49.1, 68.8), with very good partial response (VGPR) achieved in 28.2 per­cent of patients. Complete response (CR) was achieved in 5.8 per­cent of patients; stringent CR (sCR) was achieved in 7.8 per­cent of patients; and partial response (PR) was achieved in 17.5 per­cent of patients.¹ The median time to response was one month (range: 0.9 to 2.8 months), and the median duration of response was 13.6 months (range: 0.9+ to 14.6+ months).¹

"The recent approval of DARZALEX is sig­nif­i­cant for patients and clinicians who urgently need new options and regi­mens. This mile­stone underscores the versatility of DARZALEX with a range of treat­ment regi­mens," said Peter F. Lebowitz, M.D., Ph.D., Global Oncology Head, Janssen Research & Development, LLC. "We look for­ward to con­tinued study of dara­tu­mu­mab in earlier stages of multiple myeloma and other cancers."

Overall, the safety of the DARZALEX com­bi­na­tion ther­apy was con­sis­tent with the known safety profiles of DARZALEX mono­therapy and poma­lido­mide plus dexa­meth­a­sone, re­spec­tive­ly. Warnings and precautions in the Prescribing Information in­clude: in­fusion reac­tions, inter­fer­ence with cross-matching and red blood cell anti­body screen­ing, neutro­penia and thrombo­cytopenia.¹ In the EQUULEUS trial, the most frequent (>20 per­cent) adverse reac­tions (ARs) were in­fusion reac­tions (50 per­cent), diarrhea (38 per­cent), con­sti­pa­tion (33 per­cent), nausea (30 per­cent), vomiting (21 per­cent), fatigue (50 per­cent), pyrexia (25 per­cent), upper res­pira­tory tract in­fec­tion (50 per­cent), muscle spasms (26 per­cent), back pain (25 per­cent), arthralgia (22 per­cent), dizzi­ness (21 per­cent), insomnia (23 per­cent), cough (43 per­cent) and dyspnea (33 per­cent).¹ The over­all in­ci­dence of serious ARs was 49 per­cent.1 Serious ARs (Grade 3/4) reported in ≥5 per­cent of patients in­cluded pneu­monia (7 per­cent).¹ Thirteen per­cent of patients dis­con­tinued ther­apy due to an AR.¹ The most common treat­ment-emergent hematology laboratory ab­nor­mal­i­ties were neutro­penia (95 per­cent), lymphopenia (94 per­cent), thrombo­cytopenia (75 per­cent) and anemia (57 per­cent).¹ The most common Grade 3 treat­ment-emergent hematology laboratory ab­nor­mal­i­ties were lymphopenia (45 per­cent), neutro­penia (36 per­cent), anemia (30 per­cent) and thrombo­cytopenia (10 per­cent).¹ The most common Grade 4 treat­ment-emergent hematology laboratory ab­nor­mal­i­ties were neutro­penia (46 per­cent), lymphopenia (26 per­cent) and thrombo­cytopenia (10 per­cent).¹

The Phase 1b EQUULEUS study in­cluded 103 patients with multiple myeloma who had received a prior PI and an immuno­modu­la­tory agent.¹ Patients received 16 mg/kg of DARZALEX in com­bi­na­tion with poma­lido­mide and low-dose dexa­meth­a­sone until disease pro­gres­sion.¹ The median patient age was 64 years with 8 per­cent of patients aged 75 or older.¹ Patients in the study had received a median of four prior lines of ther­apy, and 74 per­cent of patients had received prior au­tol­o­gous stem cell trans­plant (ASCT).¹ Ninety-eight per­cent of patients received prior bor­tez­o­mib treat­ment and 33 per­cent of patients received prior car­filz­o­mib treat­ment. All patients received prior lena­lido­mide treat­ment, with 98 per­cent of patients pre­vi­ously treated with the com­bi­na­tion of bor­tez­o­mib and lena­lido­mide. Eighty nine per­cent of patients were refractory to lena­lido­mide, 71 per­cent were refractory to bor­tez­o­mib and 64 per­cent of patients were refractory to bor­tez­o­mib and lena­lido­mide.¹

The rec­om­mended dose of DARZALEX is 16 mg/kg body weight admin­istered as an in­tra­venous in­fusion.¹ The dosing schedule for DARZALEX in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone begins with weekly admin­istra­tion (weeks 1-8) and reduces in frequency over time to every two weeks (weeks 9-24) and ultimately every four weeks (week 25 onwards until disease pro­gres­sion).¹

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 DARZALEX.6 DARZALEX is com­mer­cial­ized in the U.S. by Janssen Biotech, Inc. For full Prescribing Information, please visit www.DARZALEX.com.

About DARZALEX® (dara­tu­mu­mab) Injection, for Intravenous Infusion

DARZALEX® (dara­tu­mu­mab) injection for in­tra­venous use is the first CD38-directed anti­body approved any­where in the world.² CD38 is a surface protein that is highly ex­pressed across multiple myeloma cells, re­gard­less of disease stage.⁷ 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.¹ A subset of myeloid derived sup­pressor cells (MDSCs), CD38+ regu­la­tory T cells (Tregs) and CD38+ B cells (Bregs) were de­creased by DARZALEX.¹ 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.^8,9,10,11,12 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.^13,14,15 DARZALEX was the first CD38-directed anti­body 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.^16,17 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.^18,19 Relapsed cancer means the disease has returned after a period of initial, partial or com­plete remission.²⁰ Globally, it is esti­mated that 124,225 people were diag­nosed and 87,084 died from the disease in 2015.^21,22 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.²³

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 DARZALEX's poten­tial benefits and further devel­op­ment of dara­tu­mu­mab. 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: 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; manu­fac­tur­ing dif­fi­culties or delays; 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 1, 2017, in­­clud­ing under "Item 1A. Risk Factors" and "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. 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.

References

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Source: Janssen Biotech, Inc.