• In the ELOQUENT-3 trial, treat­ment with Empliciti plus poma­lido­mide and dexa­meth­a­sone (EPd) doubled median pro­gres­sion-free sur­vival and over­all re­sponse rate versus poma­lido­mide and dexa­meth­a­sone (Pd)¹
• Low dis­con­tinu­a­tion rates due to adverse reac­tions were observed with both EPd and Pd alone¹
• Empliciti, when used in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone, can be admin­istered once monthly after first two cycles¹

Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE: BMY) to­day an­nounced that the U.S. Food and Drug Admin­istra­tion (FDA) approved Empliciti (elo­tuzu­mab) in­jec­tion for intra­venous use in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone (EPd) for the treat­ment of adult patients with mul­ti­ple myeloma who have re­ceived at least two prior ther­a­pies, in­­clud­ing lena­lido­mide and a pro­te­a­some in­hib­i­tor.¹ In ELOQUENT-3, a ran­dom­ized, open-label, Phase 2 trial, EPd dem­onstrated ben­e­fit in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma, doubling both median pro­gres­sion-free sur­vival (PFS) and over­all re­sponse rate (ORR) versus poma­lido­mide and dexa­meth­a­sone (Pd).¹

“Empliciti plus poma­lido­mide and dexa­meth­a­sone has been proven to extend the time that cer­tain patients live without dis­ease pro­gres­sion, giving health care professionals an ef­fec­tive new tool to tackle this relentless cancer,”^1,2 said Joseph E. Eid, M.D., senior vice pres­i­dent and head of Medical, Bristol-Myers Squibb. “Today’s ap­prov­al reinforces the importance of Immuno-Oncology in blood cancers and ex­pands the role of Empliciti to address the needs of re­lapsed or re­frac­tory mul­ti­ple myeloma patients.”

Empliciti with poma­lido­mide and dexa­meth­a­sone is asso­ci­ated with Warnings and Precautions re­lated to: in­fusion reac­tions, in­fec­tions, sec­ond­ary pri­mary malig­nan­cies, hepato­tox­ic­ity, inter­fer­ence with deter­mi­na­tion of com­plete re­sponse, pregnancy/females and males of reproductive poten­tial and adverse reac­tions.¹ Please see the detailed im­por­tant safety in­for­ma­tion below.

Following priority review by the FDA, EPd is the first triplet com­bi­na­tion to be approved based on a ran­dom­ized clin­i­cal trial using Pd as a comparator.^3,4 Results from the trial in­clude:

• Progression-free survival (primary end­point, investigator-assessed):^1,3 EPd reduced the risk of disease pro­gres­sion by 46% (hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.34 to 0.86, p=0.0078), demonstrating a median PFS of 10.25 months (95% CI: 5.59 to non-estimable [NE]) vs. 4.67 months (95% CI: 2.83 to 7.16) for Pd alone after a minimum follow-up of 9.1 months.¹
• Overall response rate (secondary end­point, investigator-assessed):^1,3 Response rates doubled in patients receiving EPd (53.3%; n=32/60 [95% CI: 40.0 to 66.3]) compared with patients receiving Pd alone (26.3%; n=15/57 [95% CI: 15.5 to 39.7]; p=0.0029), with very good partial responses or better seen in 20% of EPd-treated patients (n=12) and 8.8% of Pd-treated patients (n=5).¹
• Safety: Serious adverse reac­tions were reported in 22% of patients treated with EPd and in 15% of patients treated with Pd.¹ Discontinuation of any component of the treat­ment regi­men due to adverse reac­tions occurred in 5.0% of patients in the EPd arm, compared to 1.8% of patients in the control arm.¹

“Despite remarkable recent inno­va­ts with novel ther­a­pies for the treat­ment of mul­ti­ple myeloma, many patients still face poor out­comes, and par­tic­u­larly in the re­lapsed and re­lapsed, re­frac­tory setting,”⁵ said Paul Richardson, M.D., clin­i­cal pro­gram leader and director of clin­i­cal re­search of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer In­sti­tute. “This new regi­men of elotuzumab com­bined with poma­lido­mide and dexa­meth­a­sone not only extended the time to dis­ease pro­gres­sion versus a standard of care but also doubled the re­sponse rate in some patients whose prior treat­ments had failed them.^1,6 Thus to be able to offer an alter­na­tive with a meaningful clin­i­cal ben­e­fit is an im­por­tant and sig­nif­i­cant mile­stone for our patients.”^1,4

Approximately 31,000 people in the United States will be diag­nosed with mul­ti­ple myeloma this year.⁷ A common char­ac­ter­istic for many patients is that they ex­peri­ence mul­ti­ple relapses, which means that the cancer returns after a period of remission.^8,9

“Relapse can be overwhelming and extremely chal­leng­ing for mul­ti­ple myeloma patients, par­tic­u­larly after they have already tried sev­er­al ther­a­pies,”¹⁰ said Paul Giusti, pres­i­dent and chief exec­u­tive officer of the Multiple Myeloma Re­search Foundation. “Empliciti, in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone, is an ex­cit­ing new op­tion for patients with re­lapsed or re­frac­tory myeloma.”

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

About ELOQUENT-3

ELOQUENT-3 was a ran­dom­ized, open-label Phase 2 study eval­u­ating the addi­tion of Empliciti to poma­lido­mide and dexa­meth­a­sone versus poma­lido­mide and dexa­meth­a­sone in 117 patients with mul­ti­ple myeloma who re­ceived two or more prior ther­a­pies and were either re­frac­tory or re­lapsed and re­frac­tory to lena­lido­mide and a pro­te­a­some in­hib­i­tor.^1,3,4 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.¹ The approved dose of Empliciti, when used in com­bi­na­tion with poma­lido­mide and dexa­meth­a­sone, is 10 mg/kg admin­istered in­tra­venously every week for the first two 28-day cycles, followed by 20 mg/kg every four weeks until dis­ease pro­gres­sion or unacceptable toxicity.¹

The pri­mary ef­fi­cacy out­come measure of the trial was PFS as de­ter­mined by the in­ves­ti­ga­tor.^1,3 The sec­ond­ary ef­fi­cacy out­come measure of ORR in­cluded com­plete, stringent-complete, very good partial and partial re­sponse rates as de­ter­mined by in­ves­ti­ga­tor assess­ment, based on the Inter­na­tional Myeloma Work­ing Group criteria.^1,3 Data from the ELOQUENT-3 trial were pre­sented at the 23rd Congress of the Euro­pean He­ma­tol­ogy Asso­ci­a­tion in June 2018.⁴

Select Safety Profile for the ELOQUENT-3 Trial

The most fre­quent serious adverse reac­tions in the pop­u­la­tion eval­u­ated for safety (n=60 in the EPd arm and n=55 in the Pd arm) were pneu­monia (13% vs. 11%) and res­pira­tory tract in­fec­tion (7% vs. 3.6%).¹ Infusion reac­tions were reported in 3.3% of patients treated with EPd.¹ Adverse reac­tions that oc­curred with a >/=10% in­ci­dence for Empliciti plus poma­lido­mide and dexa­meth­a­sone-treated patients and >/=5% in­ci­dence than poma­lido­mide and dexa­meth­a­sone-treated patients were con­sti­pa­tion (22% vs. 11%), hyperglycemia (20% vs. 15%), pneu­monia (18% vs. 13%), diarrhea (18% vs. 9%), res­pira­tory tract in­fec­tion (17% vs. 9%), bone pain (15% vs. 9%), dyspnea (15% vs. 7%), muscle spasms (13% vs. 5%), edema periph­eral (13% vs. 7%) and lymphopenia (10% vs. 1.8%).¹

INDICATIONS

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 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.

EMPLICITI is avail­able for in­jec­tion for in­tra­venous use in 300 mg and 400 mg vials.

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 <2X the upper limit were 2.5% (ERd) vs 0.6% (Rd). Of 8 patients experiencing hepatotoxicity, 2 patients discontinued treatment while 6 patients had resolution and continued. Monitor liver enzymes periodically. Stop EMPLICITI upon ≥Grade 3 elevation of liver enzymes. Continuation of treatment may be considered after return to baseline values.

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 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 for the treat­ment of patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies.

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 inno­va­t 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 Bristol-Myers Squibb’s Patient Access Support

Bristol-Myers Squibb remains com­mit­ted to providing assistance so that cancer patients who need our med­i­cines can access them and expedite time to ther­apy.

BMS Access Support®, the Bristol-Myers Squibb patient access and reim­burse­ment pro­gram, is de­signed to help appro­pri­ate patients ini­ti­ate and main­tain access to BMS med­i­cines during their treat­ment journey. BMS Access Support offers ben­e­fit in­ves­ti­ga­tion, prior authori­za­tion assistance, as well as co-pay assistance for eli­gible, com­mer­cially insured patients. More in­for­ma­tion about our access and reim­burse­ment sup­port can be obtained by calling BMS Access Support at 1-800-861-0048 or by visiting www.bmsaccesssupport.com.

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. 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.

References

1. Empliciti Prescribing Information. Empliciti U.S. Product Information. Last Updated: November 2018. Princeton, NJ: Bristol-Myers Squibb Company.
2. Ravi P, Kumar S, Cerhan J, et al. Defining cure in multiple myeloma: a comparative study of outcomes of young individuals with myeloma and curable hematologic malignancies. Blood Cancer J. 2018;8-26.
3. ClinicalTrials.gov. An Investigational Immuno-Therapy Trial of Pomalidomide and Low-Dose Dexamethasone With or Without Elotuzumab to Treat Refractory and Relapsed and Refractory Multiple Myeloma (ELOQUENT-3). https://clinicaltrials.gov/ct2/show/NCT02654132?term=NCT02654132&rank=1. Accessed September 25, 2018.
4. Dimopoulos M, Dytfeld D, Grosicki S, et al. Elotuzumab plus Pomalidomide/Dexamethasone (EPD) VS PD for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): Results from the Phase 2, Randomized Open-Label ELOQUENT-3 Study. (Slides from Oral Presentation) Presentation: The 23rd Congress of The European Hematology Association; June 2018; Stockholm, Sweden.
5. Kurtin S. Relapsed or relapse/refractory multiple myeloma. J Adv Pract Oncol. 2013;4.
6. NCCN Clinical Practice Guidelines in Oncology. Multiple Myeloma. 2018.
7. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7-30.
8. Rajkumar SV. Multiple myeloma: 2018 update on diagnosis, risk-stratification and management. Am J Hematol. 2016 Jul;91(7):719-34.
9. National Cancer Institute. NCI Dictionary of Cancer Terms: Relapse. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/relapse. Accessed September 24, 2018.
10. Hulin C, Hansen T, Heron L, et al. Living with the burden of relapse in multiple myeloma from the patient and physician perspective. Leuk Res. 2017;59:75-84.

Source: Bristol-Myers Squibb.