First and only immunostimulatory anti­body approved in the Euro­pean Union for mul­ti­ple myeloma

Accelerated assess­ment and ap­prov­al based on long-term data from ELOQUENT-2, which eval­u­ated Empliciti in com­bi­na­tion with Revlimid® (lena­lido­mide) and dexa­meth­a­sone (Rd)

ELOQUENT-2 dem­onstrated the Empliciti com­bi­na­tion de­liv­ered a 53% rel­a­tive im­prove­ment in pro­gres­sion-free sur­vival vs. Rd alone at three years (23% vs. 15%)

Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE:BMY) and AbbVie (NYSE:ABBV) an­nounced to­day that the Euro­pean Com­mis­sion has approved Empliciti™ (elo­tuzu­mab) for the treat­ment of mul­ti­ple myeloma as com­bi­na­tion ther­apy with Revlimid® (lena­lido­mide) and dexa­meth­a­sone in patients who have re­ceived at least one prior ther­apy. Empliciti is now the first and only immunostimulatory anti­body approved for mul­ti­ple myeloma in the Euro­pean Union (EU).

The ap­prov­al is based on data from the ran­dom­ized, open-label, Phase 3 ELOQUENT-2 study, which eval­u­ated Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (ERd) versus lena­lido­mide and dexa­meth­a­sone (Rd) alone. The co-primary end­points of this study, pro­gres­sion-free sur­vival (PFS) as assessed by hazard ratio (HR) and over­all re­sponse rate (ORR), were achieved, with extended follow-up data showing a 53% rel­a­tive im­prove­ment in PFS rate at three years (23% versus 15%). Addi­tionally, a pre-specified interim analysis for over­all sur­vival (OS) found a pos­i­tive trend favoring the Empliciti com­bi­na­tion versus Rd alone (HR=0.77 [95% CI: 0.61, 0.97, 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, and the final analysis is pend­ing. Empliciti with lena­lido­mide and dexa­meth­a­sone 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 detailed Important Safety In­for­ma­tion below.

“At Bristol-Myers Squibb, we are com­mit­ted to de­livering pioneering med­i­cines with the goal of revolutionizing the way cancer is treated for patients who in­spire our work each and every day,” said Emmanuel Blin, senior vice pres­i­dent and head of Commercialization, Policy and Operations, Bristol-Myers Squibb. “With the ap­prov­al of Empliciti in the EU, we are proud to extend our Immuno-Oncology science to mul­ti­ple myeloma patients in Europe who have re­ceived at least one prior ther­apy.”

In ELOQUENT-2, Empliciti was eval­u­ated in patients who had re­ceived one to three prior ther­a­pies. The study dem­onstrated that the ERd regi­men re­­sulted in a 32% re­duc­tion in the risk of dis­ease pro­gres­sion or death com­pared to Rd alone (HR=0.68 [97.61% CI: 0.55, 0.85, p=0.0001]). The ERd regi­men also showed a 21% rel­a­tive im­prove­ment in PFS rate at one year (68% versus 56%) and a 50% rel­a­tive im­prove­ment in PFS rate at two years (39% versus 26%) com­pared to Rd alone. The ERd regi­men dem­onstrated a sig­nif­i­cant im­prove­ment in ORR of 78.5% (95% CI: 73.6-82.9; p=0.0002) versus 65.5% in the Rd arm (95% CI: 60.1-70.7). 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) versus 21.22 months (95% CI: 18.07, 23.20) (HR=0.62 [95% CI: 0.50, 0.77]). These data were initially reported at the 57th American Society of He­ma­tol­ogy Annual Meeting in De­cem­ber 2015.

The most common adverse reac­tions (all grades) in ERd and Rd (>10%), re­spec­tive­ly, were diarrhea (59.2%, 49.3%), pyrexia (43.0%, 27.7%), fatigue (40.0%, 34.7%), cough (33.2%, 20.3%), nasopharyngitis (29.5%, 27.7%), upper res­pira­tory tract in­fec­tion (25.2%, 22.7%), lymphopenia (17.6%, 13.6%), headache (17.2%, 9.6%), pneu­monia (15.6%, 12.9%) and herpes zoster (10.0%, 5.7%).

“Today’s de­ci­sion of the Euro­pean Com­mis­sion is ex­cel­lent news for re­lapsed and re­frac­tory mul­ti­ple myeloma patients,” said Sarper Diler, Pres­i­dent of Myeloma Patients Europe. “Multiple myeloma has had a dif­fi­cult-to-treat history, and at Myeloma Patients Europe, we are com­mit­ted to ensuring these patients living in any Euro­pean country are able to access new, inno­va­tive med­i­cines, like Empliciti.”

“Empliciti rep­re­sents an im­por­tant new treat­ment op­tion for patients with mul­ti­ple myeloma and health­care providers who are treating this cancer in Europe,” said Michael Severino, M.D., exec­u­tive vice pres­i­dent of re­search and devel­op­ment and chief scientific officer, AbbVie. “AbbVie is proud to be part of the team that devel­oped Empliciti and pleased to be part­nering with Bristol-Myers Squibb to bring this new ther­apy to pre­vi­ously treated mul­ti­ple myeloma patients.”

About ELOQUENT-2

ELOQUENT-2 (CA204-004) is a Phase 3, open-label, ran­dom­ized study eval­u­ating Empliciti in com­bi­na­tion with Rd versus Rd alone in patients with re­lapsed or re­frac­tory mul­ti­ple myeloma. The trial ran­dom­ized 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.

“As mul­ti­ple myeloma is largely incurable and is often char­ac­ter­ized by a cycle of remission and relapse, there is a crit­i­cal need for new ther­a­pies for patients that work in unique and inno­va­tive ways,” said Antonio Palumbo, M.D., study in­ves­ti­ga­tor and chief of the Myeloma Unit, ­De­part­ment of Oncology, Uni­ver­sity of Torino in Torino, Italy. “In clin­i­cal trials, Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone de­liv­ered a sig­nif­i­cant ben­e­fit in pro­gres­sion-free sur­vival com­pared to lena­lido­mide and dexa­meth­a­sone alone, which could make a meaningful dif­fer­ence in the lives of patients struggling with this serious dis­ease.”

Discontinuation rates due to adverse reac­tions were similar across the ERd and Rd arms (8.7%, 12.9%). The most fre­quent serious adverse reac­tions (Grade 3-4) in ERd and Rd were lymphopenia (12.7%, 7.4%), pneu­monia (10.5%, 8.1%), fatigue (6.4%, 6.2%), diarrhea (3.7%, 3.1%) and deep vein thrombosis (3.5%, 1.7%). The most common adverse reac­tions in ERd and Rd (>20%), re­spec­tive­ly, were diarrhea (59.2%, 49.3%), pyrexia (43.0%, 27.7%), fatigue (40.0%, 34.7%), cough (33.2%, 20.3%), nasopharyngitis (29.5%, 27.7%) and upper res­pira­tory tract in­fec­tion (25.2%, 22.7%).

Infusion reac­tions oc­curred in 10% of patients treated with ERd; these adverse reac­tions were Grade 3 or lower (Grade 3, 1%; Grade 4, 0%). 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.

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. Patients often ex­peri­ence a cycle of remission and relapse, and once a patient first relapses, their prog­nosis worsens with progressively faster relapses through each sub­se­quent line of ther­apy. 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.

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

At Bristol-Myers Squibb, we have a vision for the future of cancer care that is focused on Immuno-Oncology, now con­sidered a major treat­ment modality alongside surgery, radi­a­tion and chemo­ther­apy for cer­tain types of cancer.

We have a com­pre­hen­sive clin­i­cal port­folio of inves­ti­ga­tional and approved Immuno-Oncology agents, many of which were discovered and devel­oped by our scientists. We pioneered the re­search lead­ing to the first regu­la­tory ap­prov­al for the com­bi­na­tion of two Immuno-Oncology agents and con­tinue to study the role of com­bi­na­tions in cancer.

Our col­lab­o­ration with academia, as well as small and large bio­tech com­pa­nies, is responsible for re­search­ing the poten­tial Immuno-Oncology and non-Immuno-Oncology com­bi­na­tions, with the goal of providing new treat­ment op­tions in clin­i­cal prac­tice.

At Bristol-Myers Squibb, we are com­mit­ted to changing sur­vival ex­pec­ta­tions in hard-to-treat cancers and the way patients live with cancer.

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 in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone is approved in the United States, and the safety and ef­fi­cacy of Empliciti is being eval­u­ated by other health author­i­ties.

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

U.S. 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.

U.S. 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

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, 2015 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 2015 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.

Revlimid is a registered trademark of Celgene Corpo­ra­tion. All other trademarks are property of their re­spec­tive­ owners.

Source: Bristol-Myers Squibb.