Positive opinion based on re­duc­tion in the risk of dis­ease pro­gres­sion or death with Empliciti in com­bi­na­tion with standard of care regi­men for mul­ti­ple myeloma dem­onstrated in ELOQUENT-2 study

Princeton, NJ (Press Release) – Bristol-Myers Squibb Com­pany (NYSE:BMY) and AbbVie (NYSE:ABBV) to­day an­nounced that the Com­mit­tee for Medicinal Products for Human Use (CHMP) of the Euro­pean Medicines Agency (EMA) has adopted a pos­i­tive opinion rec­om­mending that Empliciti (elo­tuzu­mab), an inves­ti­ga­tional immunostimulatory anti­body, be granted ap­prov­al for the treat­ment of mul­ti­ple myeloma as com­bi­na­tion ther­apy with Revlimid® (lena­lido­mide) and dexa­meth­a­sone in patients who have re­ceived at least one prior ther­apy. The appli­ca­tion now will be reviewed by the Euro­pean Com­mis­sion, which has the authority to approve med­i­cines for the Euro­pean Union (EU).

“Today’s pos­i­tive CHMP recom­men­da­tion means we are one step closer to offering a new type of treat­ment for patients in Europe with mul­ti­ple myeloma who have re­ceived at least one prior ther­apy,” said Michael Giordano, M.D., senior vice pres­i­dent, head of De­vel­op­ment, Oncology, Bristol-Myers Squibb. “We look for­ward to the Euro­pean Com­mis­sion’s de­ci­sion and the oppor­tu­ni­ty to extend our lead­ing Immuno-Oncology science to patients with mul­ti­ple myeloma.”

The CHMP pos­i­tive opinion is based on data from the Phase 3, open-label ELOQUENT-2 study, which eval­u­ated Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone (ERd) versus lena­lido­mide and dexa­meth­a­sone (Rd) alone. The re­­sults of this trial showed a 30% re­duc­tion in the risk of dis­ease pro­gres­sion or death with ERd com­pared to Rd alone and, at the two year time point, ERd de­liv­ered a 52% rel­a­tive im­prove­ment in pro­gres­sion-free sur­vival. 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%). These re­­sults were pub­lished in The New England Journal of Medicine on June 2, 2015.

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.

On No­vem­ber 30, 2015, the U.S. Food and Drug Admin­istra­tion approved Empliciti in com­bi­na­tion with lena­lido­mide and dexa­meth­a­sone in patients with mul­ti­ple myeloma who have re­ceived one to three prior ther­a­pies. The safety and ef­fi­cacy of Empliciti is still being eval­u­ated by other health author­i­ties.

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

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.

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 US 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.

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, 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.

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 2014 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.

Source: Bristol-Myers Squibb.