• ELOQUENT-2 extended follow-up analysis of Empliciti in com­bi­na­tion with lena­lido­mide and dex­a­meth­a­sone (Rd) dem­onstrated a 44% rel­a­tive im­prove­ment in pro­gres­sion-free sur­vival at three years; re­­sults con­sis­tent with pivotal two year analysis
• Empliciti com­bi­na­tion had a median delay of one year in time to next treat­ment com­pared to Rd alone
• Pre-specified interim analysis for over­all sur­vival found a pos­i­tive trend favoring the Empliciti com­bi­na­tion versus Rd alone (HR 0.77; p=0.0257)

Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE:BMY) to­day pre­sented extended follow-up data and a pre-specified interim over­all sur­vival (OS) analysis of Empliciti in com­bi­na­tion with Revlimid^® (lena­lido­mide) and dex­a­meth­a­sone (ERd) in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma from ELOQUENT-2. The follow-up data dem­onstrated that Empliciti in com­bi­na­tion with Rd had an im­prove­ment in pro­gres­sion-free sur­vival (PFS) with a hazard ratio (HR) of 0.73 (95% CI: 0.60, 0.89; p=0.0014) versus Rd alone. This re­­sult was con­sis­tent with the im­prove­ment in PFS that was observed at the time of the pri­mary analysis (HR 0.70 [95% CI: 0.57, 0.85; p = 0.0004]).

The Empliciti com­bi­na­tion delayed the need for sub­se­quent myeloma ther­apy by a median of one year com­pared to Rd alone. A pre-specified interim analysis of OS found a pos­i­tive trend favoring the Empliciti combi­na­tion versus Rd alone (HR 0.77; [{95% CI: 0.61, 0.97; 98.6% CI: 0.58, 1.03}; p=0.0257]), though at the time of the interim analysis the OS end­point had not reached the pre-determined threshold for statistical sig­nif­i­cance. Patients will con­tinue to be followed for sur­vival. Updated safety and tol­er­a­bil­ity data were con­sis­tent with pre­vi­ous findings. Common Grade 3 or 4 adverse events in­cluded neu­tro­penia (26%), anemia (15%), fatigue (9%), and diarrhea (5%).

These data from ELOQUENT-2, a ran­dom­ized, open-label, Phase 3 study (Abstract #28) were pre­sented at the 57th American Society of He­ma­tol­ogy (ASH) Annual Meeting and Exposition in Orlando, FL.

“The Empliciti extended follow-up re­­sults provide physicians with addi­tional insight into the poten­tial ben­e­fit this new treat­ment may offer patients with re­lapsed or re­frac­tory mul­ti­ple myeloma,” said Paul G. Richardson, M.D., Clinical Program Leader and Director of Clinical Re­search, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer In­sti­tute. “Empliciti rep­re­sents a new ap­proach in mul­ti­ple myeloma treat­ment of directly activating the body’s im­mune sys­tem, and it is very en­cour­ag­ing to see these data dem­onstrate the ef­fi­cacy ben­e­fit persisted in some patients up to three years, allow­ing patients to live longer without experiencing dis­ease pro­gres­sion.”

Empliciti as com­bi­na­tion ther­apy with lena­lido­mide and dex­a­meth­a­sone was approved by the U.S. Food and Drug Admin­istra­tion on No­vem­ber 30, 2015, for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies.

“The extended follow-up and over­all sur­vival data pre­sented at ASH for our immunostimulatory anti­body, Empliciti, reinforce our com­mitment to helping im­prove out­comes for patients with mul­ti­ple myeloma,” said Michael Giordano, M.D., senior vice pres­i­dent, head of De­vel­op­ment, Oncology, Bristol-Myers Squibb. “These data fur­ther dem­onstrate Empliciti as com­bi­na­tion ther­apy provides im­proved ef­fi­cacy com­pared to lena­lido­mide and dex­a­meth­a­sone alone.”

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 co-primary end­points were PFS, as assessed by HR, and over­all re­sponse rate. Results of the pri­mary analysis of the ELOQUENT-2 study were pub­lished in The New England Journal of Medicine on June 2, 2015.

In the exploratory, extended follow-up analysis, the ERd regi­men re­­sulted in a 27% re­duc­tion in the risk of dis­ease pro­gres­sion or death (HR 0.73 [95% CI: 0.6, 0.89]) and a 44% rel­a­tive im­prove­ment in the PFS rate at three years com­pared to Rd alone. The ben­e­fit observed was con­sis­tent with the pivotal two year analysis which showed ERd 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]) and a 52% rel­a­tive im­prove­ment in PFS rate at two years. The extended follow-up analysis also showed ERd had a median delay of one year in the time to next treat­ment com­pared to Rd alone 33.35 months (95% CI: 26.15, 40.21) vs. 21.22 months (95% CI: 18.07, 23.20) (HR=0.62 [95% CI: 0.50, 0.77]). An interim analysis of OS found a pos­i­tive trend favoring the Empliciti com­bi­na­tion com­pared to Rd alone (HR 0.77; [{95% CI: 0.61, 0.97; 98.6% CI 0.58; 1.03}; p=0.0257]), though at the time of the interim analysis the OS end­point had not reached the pre-determined threshold for statistical sig­nif­i­cance. Patients will con­tinue to be followed for sur­vival.

Infusion reac­tions oc­curred in 10% of patients treated with ERd; these adverse events were Grade 3 or lower and oc­curred during the first treat­ment cycle. The most common adverse reac­tions in ERd and Rd, re­spec­tively (≥30%) were in­fec­tions (83%, 75%), fatigue (48%, 40%), diarrhea (48%, 37%), anemia (41%, 37%), pyrexia (38%, 25%), con­sti­pa­tion (36%, 28%), cough (33%, 19%), muscle spasms (30%, 27%), and neu­tro­pe­nia (34%, 43%). Adverse events of spe­cial interest in ERd and Rd, re­spec­tively, in­cluded gastro­in­tes­ti­nal disorders (81%, 68%), res­pira­tory disorders (63%, 53%), renal/urinary disorders (25%, 18%), periph­eral neu­rop­athy (15%, 9%), hyper­tension (10%, 7%), deep vein thrombosis (8%, 4%) and cardiac failure (1%, 2%). Updated safety and tol­er­a­bil­ity data were con­sis­tent with pre­vi­ous findings.

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 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 Reactions

• EMPLICITI can cause 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

• In a clinical trial of patients with multiple myeloma (N=635), 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

• In a clinical trial of patients with multiple myeloma (N=635), 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%) 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%).

Please see the full Prescribing In­for­ma­tion.

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.

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.

Endnotes:

Empliciti is a trademark of Bristol-Myers Squibb Com­pany.

Revlimid is a registered trademark of Celgene Corpo­ra­tion.

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