• Median pro­gres­sion-free sur­vival and over­all re­sponse rate doubled among patients re­ceiv­ing EPd com­pared to poma­lido­mide and low-dose dexa­meth­a­sone alone
• Second Empliciti-based com­bi­na­tion approved in Europe for patients with re­lapsed and re­frac­tory mul­ti­ple myeloma

Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE: BMY) to­day an­nounced that the Euro­pean Com­mis­sion (EC) has approved Empliciti (elo­tuzu­mab) plus poma­lido­mide and low-dose dexa­meth­a­sone (EPd) for the treat­ment of adult patients with re­lapsed and re­frac­tory mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies, in­clud­ing lena­lido­mide and a pro­te­a­some in­hib­i­tor (PI), and have dem­onstrated dis­ease pro­gres­sion on the last ther­apy. This ap­prov­al is based on data from the ELOQUENT-3 trial in which EPd doubled both median pro­gres­sion-free sur­vival (PFS) and over­all re­sponse rate (ORR) among patients with re­lapsed and re­frac­tory mul­ti­ple myeloma versus poma­lido­mide and low-dose dexa­meth­a­sone (Pd) alone.

“Multiple myeloma is a fre­quently re­cur­ring dis­ease and the chance it will return after initial treat­ment is a heavy burden for patients to carry,” said Fouad Namouni, M.D., head, Oncology De­vel­op­ment, Bristol-Myers Squibb. “We are proud that the Euro­pean Com­mis­sion has again recog­nized the role of Empliciti in helping Euro­pean patients with mul­ti­ple myeloma by approving a sec­ond Empliciti-based regi­men in the re­lapsed and re­frac­tory setting.”

EPd is the first triplet com­bi­na­tion approved in Europe based on a ran­dom­ized clin­i­cal trial using the standard of care, Pd, as a comparator. Results from ELOQUENT-3 dem­onstrated that the addi­tion of Empliciti to Pd can sig­nif­i­cantly pro­long sur­vival without dis­ease pro­gres­sion among heavily pre­treated patients with mul­ti­ple myeloma re­gard­less of the num­ber of prior ther­a­pies re­ceived. In­ves­ti­ga­tor-assessed PFS, the study’s pri­mary end­point, was 10.25 months (95% CI: 5.59 to not estimable) among patients ran­dom­ized to EPd com­pared with 4.67 months (95% CI: 2.83 to 7.16) among patients treated with Pd alone, in­di­cating a 46% re­duc­tion in risk of dis­ease pro­gres­sion (HR 0.54; 95% CI: 0.34 to 0.86; p=0.0078) be­tween EPd and Pd arms after a min­i­mum follow-up of 9.1 months. A sec­ond­ary end­point of the study, ORR, was 53.3% (95% CI: 40.0 to 66.3) com­pared with 26.3% (95% CI: 15.5 to 39.7; p=0.0029) among patients re­ceiv­ing EPd or Pd, re­spec­tive­ly.

“The ap­prov­al of this elotuzumab-based triplet com­bi­na­tion in the re­lapsed and re­frac­tory setting gives patients, and their doctors, a treat­ment alter­na­tive shown to have the poten­tial to offer patients more time living without dis­ease pro­gres­sion, coupled with a tol­er­able safety profile,” said Meletios A. Dimopoulos, M.D., pro­fessor and chairman of the ­De­part­ment of Clinical Thera­peutics at National and Kapodistrian Uni­ver­sity of Athens.

Data from the ELOQUENT-3 trial were first pre­sented at the 23rd Congress of the Euro­pean Hema­tology Asso­ci­a­tion (EHA) in 2018. Updated ef­fi­cacy re­­sults with a min­i­mum follow-up of 18.3 months were pre­sented at the 24th Congress of the EHA this year. In this exploratory analysis, a total of 40 (67%) patients were alive in the EPd arm and 29 (51%) patients were alive in the Pd arm (HR 0.54; 95% CI: 0.30 to 0.96). Median OS was not reached for the EPd treat­ment arm.

Treatment-related Grade 3-4 adverse events (AEs) were com­parable be­tween EPd and Pd groups. Any-grade in­fec­tions oc­curred in 65% of patients in both arms. Rates of the most commonly oc­curring Grade 3-4 hema­to­logic AEs, neu­tro­penia and anemia, were 13% and 10%, re­spec­tive­ly, for patients re­ceiv­ing EPd and 27% and 20%, re­spec­tive­ly, for patients re­ceiv­ing Pd, despite longer exposure within the EPd arm and similar dose intensity of poma­lido­mide be­tween arms. AEs led to dis­con­tinu­a­tion in 18% of patients in the EPd arm, com­pared with 24% of patients in the Pd arm.

The U.S. Food and Drug Admin­istra­tion (FDA) approved EPd for the treat­ment of adult patients with mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies, in­clud­ing lena­lido­mide and a PI, in No­vem­ber 2018.

Bristol-Myers Squibb and AbbVie are co-developing Empliciti, with Bristol-Myers Squibb solely re­sponsible for com­mer­cial ac­­tiv­i­ties.

About ELOQUENT-3

The Phase 2 ELOQUENT-3 trial ran­dom­ized 117 patients with re­lapsed and re­frac­tory mul­ti­ple myeloma to treat­ment with EPd (n=60) or Pd (n=57) in 28-day cycles until dis­ease pro­gres­sion or unacceptable toxicity. In the EPd arm, Empliciti was admin­istered in­tra­venously at the dose of 10 mg/kg each week for the first 2 cycles and 20 mg/kg every four week there­after. The median num­ber of treat­ment cycles was nine for the EPd arm and five for the Pd arm.

Bristol-Myers Squibb: Advancing Oncology Re­search

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our re­search is to in­crease quality, long-term sur­vival for patients and make cure a possibility. Through a unique multi­disciplinary ap­proach powered by trans­la­tional science, we har­ness our deep scientific ex­peri­ence in on­col­ogy and Immuno-Oncology (I-O) re­search to identify novel treat­ments tailored to in­di­vid­ual patient needs. Our re­searchers are devel­op­ing a diverse, pur­posefully built pipe­line de­signed to target dif­fer­en­t im­mune sys­tem path­ways and address the complex and spe­cif­ic inter­actions be­tween the tumor, its microenvironment and the im­mune sys­tem. We source inno­va­tion in­ternally, and in col­lab­o­ration with academia, gov­ern­ment, advocacy groups and bio­technology com­pa­nies, to help make the prom­ise of trans­formational med­i­cines, like I-O, a reality for patients.

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 also is 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.

Empliciti was initially approved by the FDA in 2015 in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (ELd) for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies. In 2018, Empliciti was approved by the FDA in a new 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. The ELd and EPd indi­ca­tions were sub­se­quently approved by the EC in 2016 and 2019, re­spec­tive­ly.

U.S. FDA-APPROVED INDICATIONS FOR EMPLICITI®

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

EMPLICITI® (elo­tuzu­mab) is in­di­cated in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone for the treat­ment of adult patients with mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies in­clud­ing lena­lido­mide and a pro­te­a­some in­hib­i­tor.

IMPORTANT SAFETY INFORMATION

Infusion Reactions

Infusion reac­tions were reported in 10% of patients treated with EMPLICITI in the ELOQUENT-2 trial [EMPLICITI + lena­lido­mide + dexa­meth­a­sone (ERd) vs lena­lido­mide + dexa­meth­a­sone (Rd)] and 3.3% in the ELOQUENT-3 trial [EMPLICITI + poma­lido­mide + dexa­meth­a­sone (EPd) vs poma­lido­mide + dexa­meth­a­sone (Pd)].

In the ELOQUENT-2 trial, all in­fusion reac­tions were Grade 3 or lower, with Grade 3 in­fusion reac­tions oc­curring in 1% of patients. The most common symp­toms in­cluded 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.

In the ELOQUENT-3 trial, the only in­fusion reac­tion symp­tom was chest discomfort (2%), which was Grade 1. All the patients who ex­peri­enced an in­fusion reac­tion had them during the first treat­ment cycle.

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 EMPLICITI in­fusion.

Infections

In the ELOQUENT-2 trial (N=635), in­fec­tions were reported in 81% of patients in the ERd arm and 74% in the Rd arm. Grade 3-4 in­fec­tions were 28% (ERd) and 24% (Rd). Discontinuations due to in­fec­tions were 3.5% (ERd) and 4.1% (Rd). Fatal in­fec­tions were 2.5% (ERd) and 2.2% (Rd). Oppor­tu­nistic in­fec­tions were reported in 22% (ERd) and 13% (Rd). Fungal in­fec­tions were 10% (ERd) and 5% (Rd). Herpes zoster was 14% (ERd) and 7% (Rd).

In the ELOQUENT-3 trial (N=115), in­fec­tions were reported in 65% of patients in both the EPd arm and the Pd arm. Grade 3-4 in­fec­tions were reported in 13% (EPd) and 22% (Pd). Discontinuations due to in­fec­tions were 7% (EPd) and 5% (Pd). Fatal in­fec­tions were 5% (EPd) and 3.6% (Pd). Oppor­tu­nistic in­fec­tions were reported in 10% (EPd) and 9% (Pd). Herpes zoster was reported in 5% (EPd) and 1.8% (Pd).

Monitor patients for devel­op­ment of in­fec­tions and treat promptly.

Second Primary Malig­nan­cies

In the ELOQUENT-2 trial (N=635), in­vasive sec­ond pri­mary malig­nan­cies (SPM) were 9% (ERd) and 6% (Rd). The rate of hema­to­logic malig­nan­cies was 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).

In the ELOQUENT-3 trial (N=115), in­vasive SPMs were 0% (EPd) and 1.8% (Pd).

Monitor patients for the devel­op­ment of SPMs.

Hepatotoxicity

In the ELOQUENT-2 trial (N=635), AST/ALT >3X the upper limit, total bilirubin >2X the upper limit, and alkaline phosphatase

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 avail­able data on EMPLICITI use in pregnant women to in­form a drug-associated risk of major birth defects and miscarriage.

There is a risk of fetal harm, in­clud­ing severe life-threatening human birth defects, asso­ci­ated with lena­lido­mide and poma­lido­mide, and they are con­tra­in­di­cated for use in pregnancy. Refer to the re­spec­tive­ prod­uct 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

ELOQUENT-2 trial:

• Serious adverse reac­tions were 65% (ERd) and 57% (Rd). The most frequent serious adverse reac­tions in the ERd arm com­pared to the Rd arm were: pneu­monia (15%, 11%), pyrexia (7%, 5%), 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 (62%, 52%), diarrhea (47%, 36%), pyrexia (37%, 25%), con­sti­pa­tion (36%, 27%), cough (34%, 19%), periph­eral neu­rop­athy (27%, 21%), nasopharyngitis (25%, 19%), upper res­pira­tory tract in­fec­tion (23%, 17%), de­creased appetite (21%, 13%), and pneu­monia (20%, 14%).

ELOQUENT-3 trial:

• Serious adverse reac­tions were 22% (EPd) and 15% (Pd). The most frequent serious adverse reac­tions in the EPd arm com­pared to the Pd arm were: pneu­monia (13%, 11%) and res­pira­tory tract in­fec­tion (7%, 3.6%).
• The most common adverse reac­tions in EPd arm (≥20% EPd) and Pd, re­spec­tive­ly, were con­sti­pa­tion (22%, 11%) and hyperglycemia (20%, 15%).

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 us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Face­book.

About AbbVie in Oncology

At AbbVie, we strive to discover and de­vel­op med­i­cines that de­liver trans­formational im­prove­ments in cancer treat­ment by uniquely combining our deep knowledge in core areas of biology with cutting-edge tech­nolo­gies, and by work­ing to­geth­er with our part­ners – scientists, clin­i­cal experts, industry peers, advocates, and patients. We remain focused on de­livering these trans­for­ma­tive ad­vances in treat­ment across some of the most debilitating and widespread cancers. We are also com­mit­ted to exploring solu­tions to help patients obtain access to our cancer med­i­cines. With the ac­qui­si­tions of Pharmacyclics in 2015 and Stemcentrx in 2016, our re­search and devel­op­ment efforts, and through col­lab­o­rations, AbbVie's on­col­ogy port­folio now consists of mar­keted med­i­cines and a pipe­line con­taining mul­ti­ple new mol­e­cules being eval­u­ated world­wide in more than 200 clin­i­cal trials and more than 20 dif­fer­en­t tumor types. For more in­for­ma­tion, please visit http://www.abbvie.com/our-science/therapeutic-focus-areas/oncology.html.

Bristol-Myers Squibb Forward-Looking State­ment

This press re­lease con­tains “forward-looking state­ments” within the meaning of the Private Se­cu­ri­ties Lit­i­ga­tion Reform Act of 1995 re­gard­ing, among other things, the re­search, devel­op­ment and com­mer­cial­iza­tion of pharma­ceu­tical prod­ucts. All state­ments that are not state­ments of historical facts are, or may be deemed to be, for­ward-looking state­ments. Such for­ward-looking state­ments are based on historical per­for­mance and cur­rent ex­pec­ta­tions and pro­jec­tions about our future fi­nan­cial re­­sults, goals, plans and objectives and in­volve in­her­ent risks, assump­tions and un­cer­tainties, in­clud­ing in­ternal or ex­ternal factors that could delay, divert or change any of them in the next sev­er­al years, that are dif­fi­cult to predict, may be beyond our con­trol and could cause our future fi­nan­cial re­­sults, goals, plans and objectives to differ ma­teri­ally from those ex­pressed in, or im­plied by, the state­ments. These risks, assump­tions, un­cer­tainties and other factors in­clude, among others, whether Empliciti for the addi­tional indi­ca­tions described in this re­lease will be com­mer­cially suc­cess­ful. No for­ward-looking state­ment can be guar­an­teed. Forward-looking state­ments in this press re­lease should be eval­u­ated to­geth­er with the many risks and un­cer­tainties that affect Bristol-Myers Squibb’s business and mar­ket, par­tic­u­larly those identified in the cautionary state­ment and risk factors dis­cus­sion in Bristol-Myers Squibb’s Annual Report on Form 10-K for the year ended De­cem­ber 31, 2018, as up­dated by our sub­se­quent Quar­ter­ly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Se­cu­ri­ties and Ex­change Com­mis­sion. The for­ward-looking state­ments in­cluded in this doc­u­ment are made only as of the date of this doc­u­ment and except as other­wise re­quired by appli­cable law, Bristol-Myers Squibb under­takes no obli­ga­tion to pub­licly up­date or revise any for­ward-looking state­ment, whether as a re­­sult of new in­for­ma­tion, future events, changed cir­cum­stances or other­wise.

Source: Bristol-Myers Squibb.