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European Medicines Agency Validates Bristol Myers Squibb’s Applications for Idecabtagene Vicleucel (Ide-cel, bb2121) and CC-486

May 22, 2020 Off By BusinessWire

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, N.J.–(BUSINESS WIRE)–$BMY #BMS—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 currently 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 currently 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

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
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.
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.
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.
Lonial, S., Anderson, K.C., Association of response endpoints with survival outcomes in multiple myeloma. Leukemia. 2014; 28(2): 258-268.
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.
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.