Application based on re­­sults from Phase 2 ELOQUENT-3 study

{{image}}Princeton, NJ (Press Release) - Bristol-Myers Squibb Com­pany (NYSE:BMY) to­day an­nounced that the U.S. Food and Drug Admin­istra­tion (FDA) ac­cepted its supple­mental Biologics License Appli­ca­tion (sBLA) for Empliciti (elo­tuzu­mab) in com­bi­na­tion with poma­lido­mide and low-dose dexa­meth­a­sone (EPd) for the treat­ment of patients with re­lapsed / re­frac­tory mul­ti­ple myeloma (RRMM) who have re­ceived at least two prior ther­a­pies, in­­clud­ing lena­lido­mide and a pro­te­a­some in­hib­i­tor. The FDA granted the appli­ca­tion priority review with an action date of De­cem­ber 27, 2018.

“This file ac­ceptance is an im­por­tant step in BMS’s on­go­ing efforts to ad­vance treat­ment op­tions for patients with re­lapsed / re­frac­tory mul­ti­ple myeloma,” said Jeffrey Jackson, Ph.D., he­ma­tol­ogy devel­op­ment lead, Bristol-Myers Squibb. “Given the need for new, ef­fec­tive treat­ment op­tions in this patient pop­u­la­tion, we look for­ward to work­ing with the FDA with the hope of bringing this com­bi­na­tion to patients with RRMM whose dis­ease progressed on pre­vi­ous ther­a­pies as quickly as possible.”

The appli­ca­tion is based on data from ELOQUENT-3, a ran­dom­ized Phase 2 study eval­u­ating the addi­tion of Empliciti to poma­lido­mide and low-dose dexa­meth­a­sone in patients with RRMM. Data from this study were pre­sented at the 23rd Congress of the Euro­pean He­ma­tol­ogy Asso­ci­a­tion in June.

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 RRMM who re­ceived two or more prior ther­a­pies and were either re­frac­tory or re­lapsed and re­frac­tory to lena­lido­mide and a PI. Patients were ran­dom­ized 1:1 to re­ceive either EPd (n=60) or Pd (n=57) in 28-day cycles until dis­ease pro­gres­sion or unacceptable toxicity. Patients in both the EPd and Pd arms re­ceived 4 mg of poma­lido­mide for days 1-21 of each cycle, and the weekly equivalent of 40 mg or 20 mg dexa­meth­a­sone for patients ≤75 years or >75 years, re­spec­tive­ly. In the EPd arm, elotuzumab was admin­istered at the dose of 10 mg/kg IV weekly for the first 2 cycles and 20 mg/kg monthly start­ing from cycle 3. Patients ran­dom­ized to EPd ex­peri­enced a 46% re­duc­tion in risk of dis­ease pro­gres­sion (HR 0.54; 95% CI: 0.34 to 0.86, p=0.0078) com­pared with patients ran­dom­ized to Pd alone, with median PFS, the study’s pri­mary end­point, of 10.3 months (95% CI: 5.6 to not estimable) com­pared with 4.7 months (95% CI: 2.8 to 7.2) in Pd patients. The PFS ben­e­fit ex­peri­enced among patients ran­dom­ized to EPd was con­sis­tent among patients who had re­ceived two to three prior lines of ther­apy (HR 0.55; 95% CI: 0.31 to 0.98) and four or more prior lines of ther­apy (HR 0.51; CI 95%: 0.24 to 1.08). The safety profile for EPd was con­sis­tent with prior findings for Empliciti and poma­lido­mide regi­mens.

Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Re­search

At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on re­search­ing and devel­op­ing trans­formational med­i­cines, in­­clud­ing Immuno-Oncology (I-O) thera­peutic ap­proaches, for hard-to-treat cancers that could poten­tially im­prove out­comes for these patients.

We are lead­ing the integrated scientific under­stand­ing of both tumor cell and im­mune sys­tem path­ways, through our extensive port­folio of inves­ti­ga­tional com­­pounds and approved agents. Our dif­fer­en­ti­ated clin­i­cal devel­op­ment pro­gram is studying broad patient pop­u­la­tions across more than 50 types of cancers with 24 clin­i­cal-stage mol­e­cules de­signed to target dif­fer­en­t im­mune sys­tem path­ways. Our deep ex­per­tise and inno­va­tive clin­i­cal trial designs position us to ad­vance the I-O/I-O, I-O/chemotherapy, I-O/targeted ther­a­pies and I-O radi­a­tion ther­a­pies across mul­ti­ple tumors and poten­tially de­liver the next wave of ther­a­pies with a sense of urgency. We also con­tinue to pioneer re­search that will help facilitate a deeper under­stand­ing of the role of im­mune bio­­markers and how a patient’s tumor biology can be used as a guide for treat­ment de­ci­sions throughout their journey.

We under­stand making the prom­ise of trans­formational med­i­cines like I-O ther­a­pies a reality for the many patients who may ben­e­fit from these ther­a­pies re­quires not only inno­va­tion on our part but also close col­lab­o­ra­tion with lead­ing experts in the field. Our part­ner­ships with academia, gov­ern­ment, advocacy and bio­tech com­pa­nies sup­port our collective goal of providing new treat­ment op­tions to ad­vance the standards of clin­i­cal prac­tice.

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.

U.S. FDA-APPROVED INDICATION FOR EMPLICITI

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 for EMPLICITI.

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/oncology.

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. Among other risks, there can be no guar­an­tee that Empliciti will re­ceive regu­la­tory ap­prov­al for the indi­ca­tions described herein. 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, 2017 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.

Source: Bristol-Myers Squibb.