• First and only immunostimulatory anti­body approved for mul­ti­ple myeloma
• Approval based on ELOQUENT-2, which estab­lish­ed the com­bi­na­tion of Empliciti with lena­lido­mide and dexa­metha­sone (Rd) de­liv­ered a sig­nif­i­cant pro­gres­sion-free sur­vival ben­e­fit vs. Rd alone, dem­onstrated over two years (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004])

{{image}}Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE:BMY) and AbbVie (NYSE:ABBV) to­day an­nounced the U.S. Food and Drug Admin­istration (FDA) has approved Empliciti (elo­tuzu­mab) for the treat­ment of mul­ti­ple myeloma as com­bi­na­tion ther­apy with Revlimid® (lena­lido­mide) and dexa­meth­a­sone (ERd) in patients who have re­ceived one to three prior ther­a­pies. The ap­prov­al of this first and only immuno­stimulatory anti­body for mul­ti­ple myeloma is based on data from the ran­dom­ized, open-label, Phase 3, ELOQUENT-2 study, which dem­onstrated that the ERd regi­men re­­sulted in a 30% re­duc­tion in the risk of dis­ease pro­gres­sion or death com­pared to Rd alone (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004]).

The co-primary end­points were pro­gres­sion-free sur­vival (PFS), as assessed by hazard ratio, and over­all re­sponse rate (ORR). With a min­i­mum of two years follow-up, ERd de­liv­ered a ben­e­fit in PFS that was main­tained over time, with PFS rates of 68% versus 57% at one year and 41% versus 27% at two years in the ERd and Rd arms, re­spec­tive­ly. The ERd regi­men also dem­onstrated a sig­nif­i­cant im­prove­ment in ORR, achieving an ORR of 78.5% (95% CI: 73.6% to 82.9%) versus 65.5% in the Rd arm (95% CI: 60.1% to 70.7%). The most common adverse reac­tions in ERd and Rd, re­spec­tive­ly (>20%) were fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), con­sti­pa­tion (35.5%, 27.1%), cough (34.3%, 18.9%), periph­eral neu­rop­athy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper res­pira­tory tract in­fec­tion (22.6%, 17.4%), de­creased appetite (20.8%, 12.6%), and pneu­monia (20.1%, 14.2%).

“At Bristol-Myers Squibb, we are lead­ing a revolution in cancer treat­ment that is changing ex­pec­ta­tions for patients with some of the hardest-to-treat cancers. With to­day’s ap­prov­al of Empliciti, we are pleased to now bring the prom­ise of our Immuno-Oncology re­search to patients with mul­ti­ple myeloma,” said Francis Cuss, MB Bchir, FRCP, chief scientific officer, Bristol-Myers Squibb. “Empliciti rep­re­sents a fundamentally dif­fer­en­t ap­proach of directly activating the im­mune sys­tem in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma, de­livering im­proved out­comes for those in need.”

Empliciti is avail­able for in­jec­tion for in­tra­venous use in 300 mg and 400 mg vials. The com­pany ex­pec­ts to begin shipping Empliciti within the next 48 hours. Empliciti is also under review by the Euro­pean Medicines Agency and has been granted ac­cel­er­ated assess­ment.

Discontinuation rates due to adverse reac­tions were similar across the ERd and Rd con­trol arms (6.0% vs. 6.3%). ERd is asso­ci­ated with the fol­low­ing Warnings and Precautions: Infusion Reactions, Infections, Second Primary Malig­nan­cies, Hepatotoxicity, Interference with Determination of Complete Re­sponse, Pregnancy/Females and Males of Reproductive Potential, and Adverse Reactions. Please see the detailed Important Safety In­for­ma­tion and a link to the Prescribing In­for­ma­tion below.

“Multiple myeloma remains largely incurable, with only half of patients sur­viving five years after diag­nosis,” said Sagar Lonial, M.D., chief med­i­cal officer of the Winship Cancer In­sti­tute of Emory Uni­ver­sity. “The ap­prov­al of elotuzumab (Empliciti) provides renewed hope for the mul­ti­ple myeloma com­munity who urgently need a treat­ment op­tion that extends the time patients live without their dis­ease pro­gress­ing.”

"Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone is an im­por­tant new op­tion for patients with mul­ti­ple myeloma and health­care providers who are treating this cancer," said Michael Severino, M.D., exec­u­tive vice pres­i­dent of re­search and devel­op­ment and chief scientific officer, AbbVie. "AbbVie is pleased to have part­nered with Bristol-Myers Squibb in making this new treat­ment avail­able for patients with re­lapsed or re­frac­tory mul­ti­ple myeloma."

About ELOQUENT-2

ELOQUENT-2 (CA204-004) is a ran­dom­ized, open-label, Phase 3 study eval­u­ating Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (ERd) versus lena­lido­mide and dexa­meth­a­sone (Rd) alone in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma. The trial en­rolled 646 patients who had re­ceived one to three prior ther­a­pies. Patients were ran­dom­ized 1:1 to re­ceive either Empliciti 10 mg/kg in com­bi­na­tion with Rd or Rd alone in 4-week cycles until dis­ease pro­gres­sion or unacceptable toxicity. Baseline patient demographics and dis­ease char­ac­ter­istics were well bal­anced be­tween treat­ment arms and in­cluded a meaningful portion of patients who were ≥ 65 years old, had high-risk cytogenetics, and/or were re­frac­tory to the most recent line of ther­apy. The min­i­mum follow-up for all study subjects was 24 months. The co-primary end­points were PFS, as assessed by hazard ratio, and ORR as de­ter­mined by a blinded Independent Review Com­mit­tee using the Euro­pean Group for Blood and Marrow Transplantation re­sponse criteria. Results of the ELOQUENT-2 study were pub­lished in The New England Journal of Medicine on June 2, 2015.

The study dem­onstrated that the ERd regi­men re­­sulted in a 30% re­duc­tion in the risk of dis­ease pro­gres­sion or death com­pared to Rd alone (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004]). Addi­tionally, the PFS rates in the ERd arm versus the Rd arm were 68% versus 57% at one year and 41% versus 27% at two years, re­spec­tive­ly. The ERd regi­men dem­onstrated a sig­nif­i­cant im­prove­ment in ORR, achieving an ORR of 78.5% (95% CI, 73.6% to 82.9%; p = 0.0002) in the ERd arm versus 65.5% in the Rd arm (95% CI, 60.1% to 70.7%). The median PFS in the ERd group was 19.4 months (95% CI, 16.6 to 22.2) versus 14.9 months (95% CI, 12.1 to 17.2) in the Rd group. At the time of the interim analysis, there were fewer deaths in the ERd versus Rd study arm (94 [29%] versus 116 [36%], re­spec­tive­ly).

Serious adverse reac­tions were reported in 65.4% of patients treated on the ERd arm and 56.5% for patients treated on the Rd arm. The most fre­quent serious adverse reac­tions in the ERd arm com­pared to the Rd arm were: pneu­monia (15.4%, 11%), pyrexia (6.9%, 4.7%), res­pira­tory tract in­fec­tion (3.1%, 1.3%), anemia (2.8%, 1.9%), pul­mo­nary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%). The most common adverse reac­tions in ERd and Rd, re­spec­tive­ly (>20%) are fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), con­sti­pa­tion (35.5%, 27.1%), cough (34.3%, 18.9%), periph­eral neu­rop­athy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper res­pira­tory tract in­fec­tion (22.6%, 17.4%), de­creased appetite (20.8%, 12.6%), and pneu­monia (20.1%, 14.2%). Infusion reac­tions oc­curred in 10% of patients treated with ERd; these adverse events were Grade 3 or lower (Grade 3, 1%; Grade 4, 0%) and were man­ageable. In the trial, 1% of patients dis­con­tinued due to in­fusion reac­tions and 5% of patients re­quired inter­rup­tion of the admin­istra­tion of Empliciti for a median of 25 min­utes. Grade 3/4 laboratory ab­nor­mal­i­ties that worsened from base­line and had a 10% or higher in­ci­dence for ERd patients and a 5% higher in­ci­dence than Rd patients were: lymphopenia (76.7%, 48.7%), leu­ko­penia (32.4%, 25.6%), hyperglycemia (17.0%, 10.2%), and hypo­cal­cemia (11.3% and 4.7%). Over­all, the pro­por­tion of patients who dis­con­tinued treat­ment due to adverse reac­tions was similar for the ERd and Rd arms (6.0% vs. 6.3%, re­spec­tive­ly).

“The ap­prov­al of Empliciti is an inno­va­tive ad­vancement in the treat­ment of mul­ti­ple myeloma,” said Walter M. Capone, chief exec­u­tive officer and pres­i­dent, The Multiple Myeloma Re­search Foundation. “This is an ex­cit­ing oppor­tu­ni­ty for patients who ex­peri­ence relapse and may ben­e­fit from this new immuno­therapy treat­ment."

About Empliciti

Empliciti is an immunostimulatory anti­body that spe­cif­i­cally targets Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7), a cell-surface glycoprotein. SLAMF7 is ex­pressed on myeloma cells in­de­pen­dent of cytogenetic ab­nor­mal­i­ties. SLAMF7 is also ex­pressed on Natural Killer cells, plasma cells, and at lower levels on spe­cif­ic im­mune cell subsets of dif­fer­en­ti­ated cells within the hema­to­poietic lineage.

Empliciti has a dual mech­a­nism-of-action. It directly activates the im­mune sys­tem through Natural Killer cells via the SLAMF7 path­way. Empliciti also targets SLAMF7 on myeloma cells, tagging these malignant cells for Natural Killer cell-mediated destruction via anti­body-dependent cel­lu­lar toxicity.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely responsible for com­mer­cial ac­­tiv­i­ties. Prior to ap­prov­al, Empliciti was granted Break­through Therapy Desig­na­tion by the FDA for use in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of mul­ti­ple myeloma in patients who have re­ceived one to three prior ther­a­pies. According to the FDA, Break­through Therapy Desig­na­tion is in­tended to expedite the devel­op­ment and review of drugs for serious or life-threatening con­di­tions. The criteria for Break­through Therapy Desig­na­tion re­quires pre­lim­i­nary clin­i­cal evi­dence that dem­onstrates the drug may have sub­stan­tial im­prove­ment on at least one clin­i­cally sig­nif­i­cant end­point over avail­able ther­apy.

About Bristol-Myers Squib’s Patient Support Programs

Bristol-Myers Squibb is com­mit­ted to helping patients through treat­ment with Empliciti. For sup­port and assistance, patients and physicians may call 1-844-EMPLICITI. This num­ber offers one-stop access to a range of sup­port services for patients and health­care professionals alike.

About Bristol-Myers Squibb’s Access Support

Bristol-Myers Squibb is com­mit­ted to helping patients access Empliciti and offers nu­mer­ous pro­grams to sup­port patients and providers in gaining access. BMS Access Support®, the Bristol-Myers Squibb Reimbursement Services pro­gram, is de­signed to sup­port access to BMS med­i­cines and expedite time to ther­apy through reim­burse­ment sup­port in­­clud­ing Benefit Investigations, Prior Authori­za­tion Facilitation, Appeals Assistance, and assistance for patient out-of-pocket costs. BMS Access Support assists patients and providers throughout the treat­ment journey―whether it is at initial diag­nosis or in sup­port of tran­si­tion from a clin­i­cal trial. More in­­for­ma­tion about our reim­burse­ment sup­port services can be obtained by calling 1-800-861-0048 or by visiting www.bmsaccesssupport.com. For health­care providers seek­ing Empliciti spe­cif­ic reim­burse­ment in­­for­ma­tion, please visit the BMS Access Support Product section by visiting www.bmsaccesssupportoncology.com.

About Multiple Myeloma

Multiple myeloma is a hema­to­logic, or blood, cancer that de­vel­ops in the bone mar­row. It oc­curs when a plasma cell, a type of cell in the soft center of bone mar­row, be­comes can­cer­ous and multiplies un­con­trollably. Common symp­toms of mul­ti­ple myeloma in­clude bone pain, fatigue, kidney im­pair­ment, and in­fec­tions.

Despite ad­vances in mul­ti­ple myeloma treat­ment over the last decade, less than half of patients sur­vive for five or more years after diag­nosis. A common char­ac­ter­istic for many patients is that they ex­peri­ence a cycle of remission and relapse, in which they stop treat­ment for a short time, but even­tu­ally return to a treat­ment shortly after. It is esti­mated that annually, more than 114,200 new cases of mul­ti­ple myeloma are diag­nosed and more than 80,000 people die from the dis­ease globally.

EMPLICITI (elo­tuzu­mab) INDICATIONS & IMPORTANT SAFETY INFORMATION

INDICATION

EMPLICITI™ (elo­tuzu­mab), is in­di­cated in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies.

IMPORTANT SAFETY INFORMATION

Infusion Reaction

• In a clinical trial of patients with multiple myeloma (n=365), EMPLICITI caused infusion reactions. Common symptoms include fever, chills, and hypertension. Bradycardia and hypotension also developed during infusions. In the trial, 5% of patients required interruption of the administration of EMPLICITI for a median of 25 minutes due to infusion reactions, and 1% of patients discontinued due to infusion reactions. Of the patients who experienced an infusion reaction, 70% (23/33) had them during the first dose. If a Grade 2 or higher infusion reaction occurs, interrupt the EMPLICITI infusion and institute appropriate medical and supportive measures. If the infusion reaction recurs, stop the EMPLICITI infusion and do not restart it on that day. Severe infusion reactions may require permanent discontinuation of EMPLICITI therapy and emergency treatment.
• Premedicate with dexamethasone, H1 Blocker, H2 Blocker, and acetaminophen prior to infusing with EMPLICITI.

Infections

• Infections were reported in 81.4% of patients in the EMPLICITI with lenalidomide/dexamethasone arm (ERd) and 74.4% in the lenalidomide/dexamethasone arm (Rd). Grade 3-4 infections were 28% (ERd) and 24.3% (Rd). Opportunistic infections were reported in 22% (ERd) and 12.9% (Rd). Fungal infections were 9.7% (ERd) and 5.4% (Rd). Herpes zoster was 13.5% (ERd) and 6.9% (Rd). Discontinuations due to infections were 3.5% (ERd) and 4.1% (Rd). Fatal infections were 2.5% (ERd) and 2.2% (Rd). Monitor patients for development of infections and treat promptly.

Second Primary Malig­nan­cies

• Invasive second primary malignancies (SPM) were 9.1% (ERd) and 5.7% (Rd). The rate of hematologic malignancies were the same between ERd and Rd treatment arms (1.6%). Solid tumors were reported in 3.5% (ERd) and 2.2% (Rd). Skin cancer was reported in 4.4% (ERd) and 2.8% (Rd). Monitor patients for the development of SPMs.

Hepatotoxicity

• Elevations in liver enzymes (AST/ALT greater than 3 times the upper limit, total bilirubin greater than 2 times the upper limit, and alkaline phosphatase less than 2 times the upper limit) consistent with hepatotoxicity were 2.5% (ERd) and 0.6% (Rd). Two patients experiencing hepatotoxicity discontinued treatment; however, 6 out of 8 patients had resolution and continued treatment. Monitor liver enzymes periodically. Stop EMPLICITI upon Grade 3 or higher elevation of liver enzymes. After return to baseline values, continuation of treatment may be considered.

Interference with Determination of Complete Re­sponse

• EMPLICITI is a humanized IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and possibly relapse from complete response in patients with IgG kappa myeloma protein.

Pregnancy/Females and Males of Reproductive Potential

• There are no studies with EMPLICITI with pregnant women to inform any drug associated risks.
• There is a risk of fetal harm, including severe life-threatening human birth defects associated with lenalidomide and it is contraindicated for use in pregnancy. Refer to the lenalidomide full prescribing information for requirements regarding contraception and the prohibitions against blood and/or sperm donation due to presence and transmission in blood and/or semen and for additional information.

Adverse Reactions

• Infusion reactions were reported in approximately 10% of patients treated with EMPLICITI with lenalidomide and dexamethasone. All reports of infusion reaction were Grade 3 or lower. Grade 3 infusion reactions occurred in 1% of patients.
• Serious adverse reactions were 65.4% (ERd) and 56.5% (Rd). The most frequent serious adverse reactions in the ERd arm compared to the Rd arm were: pneumonia (15.4%, 11%), pyrexia (6.9%, 4.7%), respiratory tract infection (3.1%, 1.3%), anemia (2.8%, 1.9%), pulmonary embolism (3.1%, 2.5%), and acute renal failure (2.5%, 1.9%).
• The most common adverse reactions in ERd and Rd, respectively (>20%) are fatigue (61.6%, 51.7%), diarrhea (46.9%, 36.0%), pyrexia (37.4%, 24.6%), constipation (35.5%, 27.1%), cough (34.3%, 18.9%), peripheral neuropathy (26.7%, 20.8%), nasopharyngitis (24.5%, 19.2%), upper respiratory tract infection (22.6%, 17.4%), decreased appetite (20.8%, 12.6%), and pneumonia (20.1%, 14.2%).

Please see the full Prescribing In­for­ma­tion here:

http://packageinserts.bms.com/pi/pi_empliciti.pdf

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global bio­pharma­ceu­tical com­pany whose mis­sion is to discover, de­vel­op and de­liver inno­va­tive med­i­cines that help patients prevail over serious dis­eases. For more in­­for­ma­tion about Bristol-Myers Squibb, visit www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

About AbbVie

AbbVie is a global, re­search-based bio­pharma­ceu­tical com­pany formed in 2013 fol­low­ing separation from Abbott Laboratories. The com­pany’s mis­sion is to use its ex­per­tise, ded­i­cated people and unique ap­proach to inno­va­t to de­vel­op and mar­ket ad­vanced ther­a­pies that address some of the world’s most complex and serious dis­eases. Together with its wholly-owned sub­sid­i­ary, Pharmacyclics, AbbVie employs more than 28,000 people world­wide and mar­kets med­i­cines in more than 170 countries. For fur­ther in­­for­ma­tion on the com­pany and its people, port­folio and com­mitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Face­book or LinkedIn page.

Bristol-Myers Squibb Forward-Looking State­ment

This press re­lease con­tains "forward-looking state­ments" as that term is defined in the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing the re­search, devel­op­ment and com­mer­cial­iza­tion of pharma­ceu­tical prod­ucts. Such for­ward-looking state­ments are based on cur­rent ex­pec­ta­tions and in­volve in­her­ent risks and un­cer­tain­ties, in­­clud­ing factors that could delay, divert or change any of them, and could cause actual out­comes and re­­sults to differ ma­teri­ally from cur­rent ex­pec­ta­tions. No for­ward-looking state­ment can be guar­an­teed. Forward-looking state­ments in this press re­lease should be eval­u­ated to­geth­er with the many un­cer­tain­ties that affect Bristol-Myers Squibb's business, par­tic­u­larly those identified in the cautionary factors dis­cus­sion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended De­cem­ber 31, 2014 in our Quar­ter­ly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb under­takes no obli­ga­tion to pub­licly up­date any for­ward-looking state­ment, whether as a re­­sult of new in­­for­ma­tion, future events or other­wise.

AbbVie Forward-Looking State­ments

Some state­ments in this news re­lease may be for­ward-looking state­ments for pur­poses of the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995. The words "be­lieve," "expect," "antic­i­pate," "project" and similar ex­pres­sions, among others, generally identify for­ward-looking state­ments. AbbVie cautions that these for­ward-looking state­ments are subject to risks and un­cer­tain­ties that may cause actual re­­sults to differ ma­teri­ally from those in­di­cated in the for­ward-looking state­ments. Such risks and un­cer­tain­ties in­clude, but are not lim­ited to, chal­lenges to in­tel­lec­tual property, com­pe­ti­tion from other prod­ucts, dif­fi­culties in­her­ent in the re­search and devel­op­ment process, adverse lit­i­ga­tion or gov­ern­ment action, and changes to laws and reg­u­la­tions appli­­cable to our industry. Addi­tional in­­for­ma­tion about the economic, competitive, gov­ern­mental, tech­no­log­i­cal and other factors that may affect AbbVie's op­er­a­tions is set forth in Item 1A, "Risk Factors," in AbbVie's 2014 Annual Report on Form 10-K, which has been filed with the Se­cu­ri­ties and Ex­change Com­mis­sion. AbbVie under­takes no obli­ga­tion to re­lease pub­licly any revisions to for­ward-looking state­ments as a re­­sult of sub­se­quent events or devel­op­ments, except as re­quired by law.

Endnotes:

Empliciti is a trademark of Bristol-Myers Squibb Com­pany. BMS Access Support is a registered trademark of Bristol-Myers Squibb Com­pany.

Revlimid is a registered trademark of Celgene Corpo­ra­tion.

© 2015 Bristol-Myers Squibb Com­pany. All rights reserved.