Applications based on pos­i­tive results from pivotal KarMMa study in re­lapsed and re­frac­tory mul­ti­ple myeloma and QUAZAR®-AML-001 study in acute myeloid leukemia

Princeton, NJ (Press Release) – Bristol Myers Squibb (NYSE: BMY) to­day an­nounced that the Euro­pean Medicines Agency (EMA) has val­i­dated its Marketing Authori­za­tion Appli­ca­tions (MAA) for both idecabtagene vicleucel (ide-cel, bb2121) and CC-486. Validation of each appli­ca­tion con­firms the re­spec­tive sub­missions are com­plete and begins the EMA’s centralized review process.

The MAA for ide-cel, the com­pany’s inves­ti­ga­tional B-cell maturation an­ti­gen (BCMA)-directed chi­meric an­ti­gen re­cep­tor (CAR) T cell immuno­therapy co-developed with bluebird bio, Inc., is for the treat­ment of adult patients with mul­ti­ple myeloma who have re­ceived at least three prior ther­a­pies, in­clud­ing an immuno­modu­la­tory agent, a pro­te­a­some in­hib­i­tor and an anti-CD38 anti­body. Ide-cel was granted Accelerated Assessment status by the EMA in March, reducing the max­i­mum timeframe for review of the appli­ca­tion to 150 days.

“Europe has one of the highest in­ci­dence rates of mul­ti­ple myeloma, and patients who have re­lapsed and are re­frac­tory to standard treat­ment regi­mens are in need of treat­ment op­tions to im­prove out­comes,¹” said Stanley Frankel, M.D., senior vice pres­i­dent, Cellular Therapy De­vel­op­ment, Bristol Myers Squibb. “We will con­tinue to work with the EMA to bring ide-cel to patients in the Euro­pean Union who are battling this aggressive blood cancer.”

The MAA for CC-486 is for the main­te­nance treat­ment of adult patients with acute myeloid leukemia (AML), who achieved com­plete remission (CR) or CR with incomplete blood count re­cov­ery (CRi), fol­low­ing induction ther­apy with or without con­sol­i­da­tion treat­ment, and who are not can­di­dates for, or who choose not to proceed to, hema­to­poietic stem cell trans­plan­ta­tion.

“For patients with AML, main­taining remission remains an extremely im­por­tant factor in the treat­ment of their dis­ease,” said Noah Berkowitz, M.D., Ph.D., senior vice pres­i­dent, Global De­vel­op­ment, He­ma­tol­ogy, Bristol Myers Squibb. “This val­i­da­tion is an im­por­tant step to­ward making CC-486 avail­able to eli­gible patients in the Euro­pean Union, who are in need of treat­ment op­tions with the poten­tial to de­crease their risk of relapse and extend their over­all sur­vival.”

Results sup­port­ing the ide-cel appli­ca­tion came from the pivotal Phase 2 KarMMa study, which eval­u­ated the ef­fi­cacy and safety of ide-cel in heavily pre-treated patients with re­lapsed and re­frac­tory mul­ti­ple myeloma. The study met its pri­mary end­point of over­all re­sponse rate and key sec­ond­ary end­point of com­plete re­sponse rate. The safety results were con­sis­tent with pre­vi­ously reported data for ide-cel.

The CC-486 appli­ca­tion is based on the ef­fi­cacy and safety results of the pivotal Phase 3 QUAZAR® AML-001 study, which met the pri­mary end­point of im­proved over­all sur­vival for patients re­ceiv­ing AML main­te­nance treat­ment with CC-486 versus placebo.

Ide-cel and CC-486 are inves­ti­ga­tional ther­a­pies that are not approved for any in­di­ca­tion in any ge­­og­ra­phy.

About Ide-cel

Ide-cel is a B-cell maturation an­ti­gen (BCMA)-directed ge­net­ic­ally modified au­tol­o­gous chi­meric an­ti­gen re­cep­tor (CAR) T cell immuno­therapy. The ide-cel CAR is com­prised of a murine extracellular single-chain variable fragment (scFv) spe­cif­ic for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recog­nizes and binds to BCMA on the surface of mul­ti­ple myeloma cells lead­ing to CAR T cell pro­lif­er­a­tion, cytokine secretion, and sub­se­quent cytolytic kill­ing of BCMA-expressing cells.

In addi­tion to the pivotal KarMMa trial eval­u­ating ide-cel in patients with re­lapsed and re­frac­tory mul­ti­ple myeloma, Bristol Myers Squibb and bluebird bio’s broad clin­i­cal de­vel­op­ment pro­gram for ide-cel in­cludes clin­i­cal stud­ies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treat­ment for patients with mul­ti­ple myeloma, in­clud­ing newly diag­nosed mul­ti­ple myeloma. For more in­for­ma­tion visit clin­i­caltrials.gov.

Ide-cel is being devel­oped as part of a Co-Development, Co-Promotion and Profit Share Agreement be­tween Bristol Myers Squibb and bluebird bio. Ide-cel was granted ac­cel­er­ated assess­ment by the Euro­pean Medicines Agency (EMA) on March 26, 2020.

About CC-486

CC-486 is an oral hypomethylating agent that in­cor­po­rates into DNA and RNA. The main mech­a­nism of action is thought to be hypomethylation of DNA, as well as direct cyto­tox­icity to ab­nor­mal hema­to­poietic cells in the bone mar­row. Hypomethylation may restore nor­mal function to genes that are crit­i­cal for dif­fer­en­tiation and pro­lif­er­a­tion. Oral dosing of CC-486 allows for extended drug exposure during each treat­ment cycle to pro­long thera­peutic ac­­tiv­ity.²

About KarMMa³

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multi­center, multinational, Phase 2 study eval­u­ating the ef­fi­cacy and safety of ide-cel in adults with re­lapsed and re­frac­tory mul­ti­ple myeloma in North America and Europe. The pri­mary end­point of the study is over­all re­sponse rate as assessed by an independent review com­mit­tee (IRC) according to the Inter­na­tional Myeloma Work­ing Group (IMWG) criteria. Complete re­sponse rate is a key sec­ond­ary end­point. Other ef­fi­cacy end­points in­clude time to re­sponse, duration of re­sponse, pro­gres­sion-free sur­vival, over­all sur­vival, minimal residual dis­ease eval­u­ated by Next-Generation Sequencing (NGS) assay and safety. The study en­rolled 140 patients, of whom 128 re­ceived ide-cel across the target dose levels of 150-450 x 10⁶ CAR+ T cells after re­ceiv­ing lym­pho­de­plet­ing chemo­ther­apy. All en­rolled patients had re­ceived at least three prior treat­ment regi­mens, in­clud­ing an immuno­modu­la­tory agent, a pro­te­a­some in­hib­i­tor and an anti-CD38 anti­body, and were re­frac­tory to their last regi­men, defined as pro­gres­sion during or within 60 days of their last ther­apy.

About QUAZAR AML-001

QUAZAR AML-001 is a Phase 3, inter­na­tional, ran­dom­ized, double-blind, placebo-controlled study of CC-486 as AML main­te­nance ther­apy in patients who achieved first com­plete remission (CR) or com­plete remission with incomplete blood count re­cov­ery (CRi) fol­low­ing intensive induction chemo­ther­apy (with or without con­sol­i­da­tion), who were in­eli­gible for hema­to­poietic stem cell trans­plant. The pri­mary end­point of the study was over­all sur­vival. Key sec­ond­ary end­points in­cluded relapse-free sur­vival (RFS), safety and tolerability, health­care resource utilization and patient-reported out­comes per the FACIT-Fatigue Scale and EQ-5D questionnaire. The study en­rolled 472 patients, ran­dom­ized 1:1 to re­ceive initially either 300 mg of CC-486 or placebo orally, once daily, for 14 days of a 28-day cycle, plus best sup­port­ive care. Patients remained on treat­ment until unacceptable toxicity or dis­ease pro­gres­sion.

About Multiple Myeloma

Multiple myeloma is a cancer of plasma cells.⁴ The cause of mul­ti­ple myeloma is not known and cur­rent there is no cure; how­ever, there are a number of treat­ment op­tions avail­able that can lead to re­sponse.⁴ Patients who have already been treated with some avail­able ther­a­pies but con­tinue to have pro­gres­sion of their dis­ease have “relapsed” and “refractory” mul­ti­ple myeloma, meaning their cancer has returned after they have re­ceived initial treat­ments. Patients with re­lapsed and re­frac­tory mul­ti­ple myeloma, that have been exposed to all three major drug classes, have fewer treat­ment op­tions and poor out­comes, in­clud­ing shorter re­sponse durations and lower over­all sur­vival.⁵ In Europe, over 48,000 people were diag­nosed with mul­ti­ple myeloma in 2018.⁶

About AML

Acute myeloid leukemia (AML) is the most common type of acute leukemia. AML starts in the bone mar­row but moves quickly into the blood. Unlike in nor­mal blood cell de­vel­op­ment, in AML, the rapid buildup of ab­nor­mal white blood cells in the bone mar­row may in­ter­fere with the pro­duc­tion of nor­mal blood cells, re­sult­ing in de­creased healthy white blood cells, red blood cells and platelets. AML is a complex, diverse dis­ease asso­ci­ated with mul­ti­ple ge­netic mutations and usually worsens quickly and can lead to death if not treated. AML has a high relapse rate, meaning fol­low­ing patients' initial re­sponse to treat­ment, their dis­ease is likely to return, signifying an unmet need to pro­long remission. There are approx­i­mately 40,000 people with AML in Europe, and this number has in­creased in recent years likely due to the aging pop­u­la­tion.⁷

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer re­search is to in­crease patients’ quality of life, long-term sur­vival and make cure a possibility. We har­ness our deep scientific ex­peri­ence, cutting-edge tech­nolo­gies and discovery plat­forms to discover, de­vel­op and de­liver novel treat­ments for patients.

Building upon our trans­for­ma­tive work and legacy in hema­tol­ogy and Immuno-Oncology that has changed sur­vival ex­pec­ta­tions for many cancers, our re­searchers are ad­vanc­ing a deep and diverse pipe­line across mul­ti­ple modalities. In the field of immune cell ther­apy, this in­cludes reg­is­tra­tional CAR T cell agents for nu­mer­ous dis­eases, and a growing early-stage pipe­line that ex­pands cell and gene ther­apy targets, and tech­nolo­gies. We are devel­op­ing cancer treat­ments directed at key bio­logical path­ways using our pro­tein homeo­stasis plat­form, a re­search ca­pa­bil­i­ty that has been the basis of our approved ther­a­pies for mul­ti­ple myeloma and several promising com­pounds in early- to mid-stage de­vel­op­ment. Our scientists are targeting dif­fer­en­t immune sys­tem path­ways to address inter­actions be­tween tumors, the microenvironment and the immune sys­tem to fur­ther ex­pand upon the progress we have made and help more patients respond to treat­ment. Combining these ap­proaches is key to de­livering poten­tial new op­tions for the treat­ment of cancer and addressing the growing issue of re­sis­tance to immuno­therapy. We source inno­va­tion in­ternally, and in col­lab­o­ration with academia, gov­ern­ment, advocacy groups and bio­technol­ogy com­pa­nies, to help make the prom­ise of trans­formational med­i­cines a reality for patients.

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, Face­book and Insta­gram.

Celgene and Juno Thera­peutics are wholly owned sub­sid­i­aries of Bristol-Myers Squibb Com­pany. In cer­tain countries outside the U.S., due to local laws, Celgene and Juno Thera­peutics are referred to as, Celgene, a Bristol Myers Squibb com­pany and Juno Thera­peutics, a Bristol Myers Squibb com­pany.

Bristol Myers Squibb Cautionary State­ment Regarding Forward-Looking State­ments

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, the possibility of un­fa­vor­able results from addi­tional stud­ies involving ide-cel, or bb2121, or CC-486, that such prod­uct can­di­dates may not re­ceive regu­la­tory ap­prov­al for the in­di­ca­tions described in this release in the cur­rent antic­i­pated timeline or at all and, if approved, whether such prod­uct can­di­dates for such 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, 2019, 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.

References

1. Cowan AJ, Allen C, Barac A, et al. Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study 2016. JAMA Oncol. 2018;4(9):1221–1227. doi:10.1001/jamaoncol.2018.2128
2. Garcia-Manero et al. Phase I study of oral azacitidine in myelo­dys­plastic syn­dromes, chronic myelomonocytic leukemia, and acute myeloid leukemia. J Clin Oncol. 2011;29(18):2521–7.
3. ClinicalTrials.gov. Efficacy and safety study of bb2121 in subjects with re­lapsed and re­frac­tory mul­ti­ple myeloma (KarMMa). Available at: https://clinicaltrials.gov/ct2/show/NCT03361748. Accessed May 2020.
4. American Cancer Society. What is Multiple Myeloma? Available at: https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed May 2020.
5. Lonial, S., Anderson, K.C., Asso­ci­a­tion of re­sponse end­points with sur­vival out­comes in mul­ti­ple myeloma. Leukemia. 2014; 28(2): 258-268.
6. WHO. Inter­na­tional Agency for Research on Cancer. Estimated number of new cases in 2018, Europe, both sexes, all ages. Available at: https://gco.iarc.fr/today/online-analysis-table?v=2018&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&include_nmsc=1&include_nmsc_other=1#collapse-by_country. Accessed: May 2020.
7. Heuser et al. Acute myeloid leukaemia in adult patients: ESMO Clinical Practice Guidelines for diag­nosis, treat­ment and follow-up. ESMO Annals of Oncology. 2020; 31(0): 0-0.

Source: Bristol-Myers Squibb.