PRINCETON, N.J.--(BUSINESS WIRE)--Bristol Myers Squibb (NYSE: BMY) today announced that the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for lisocabtagene maraleucel (liso-cel), an investigational CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adults with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B (FL3B) after at least two prior therapies. Validation of the application confirms the submission is complete and begins the EMA’s centralized review process.

Results from TRANSCEND NHL 001, the largest trial in third-line or greater R/R large B-cell lymphoma (LBCL), and additional data from the TRANSCEND WORLD study were the basis of the liso-cel application. The studies evaluated patients with R/R LBCL and included patients with a broad range of histologies and high-risk disease as well as those who received liso-cel in the outpatient setting.

“With more than 30% of patients diagnosed with diffuse large B-cell lymphoma ultimately relapsing after initial therapy and an expected overall survival of about six months for patients who have had two or more prior therapies, there is a need for new treatments,” said Stanley Frankel, M.D., senior vice president, Cellular Therapy Development, Bristol Myers Squibb.^1,2 “The EMA’s validation of our application is a critical step toward bringing liso-cel to patients in Europe.”

The EMA previously granted liso-cel access to the PRIME scheme for the treatment of R/R DLBCL and, more recently, Accelerated Assessment status, reducing the maximum timeframe to 150 days for the EMA’s Committee for Medicinal Products for Human Use (CHMP) to review the application.

Liso-cel is an investigational therapy that is not approved for use in any country.

About TRANSCEND NHL 001

TRANSCEND NHL 001 is an open-label, multicenter, pivotal Phase 1 study to determine the safety, antitumor activity and pharmacokinetics of liso-cel in patients with R/R B-cell NHL, including DLBCL, HGL, PMBCL and Grade 3B FL. Mantle cell lymphoma is investigated in a separate cohort. The primary outcome measures included treatment-related adverse events, dose-limiting toxicities and objective response rate. Key secondary outcome measures included complete response rate, duration of response and progression-free survival. The TRANSCEND program is a broad clinical program evaluating liso-cel in multiple indications and treatment lines.

About TRANSCEND WORLD

TRANSCEND WORLD is a single-arm, multi-cohort, multicenter, Phase 2 study to determine the efficacy and safety of liso-cel in patients with aggressive B-cell non-Hodgkin lymphoma (NHL). The primary outcome measure was overall response rate (ORR). Secondary outcome measures included safety, complete response rate, event-free survival, progression-free survival, overall survival, duration of response, pharmacokinetics and health-related quality of life. The study was conducted in Europe and Japan.

About Large B-cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a rapidly growing, aggressive disease and the most common form of non-Hodgkin lymphoma (NHL), accounting for one out of every three cases diagnosed.³ More than two-thirds of patients will not respond to or will relapse following second-line treatment.³ For patients who relapse or do not respond to initial therapies, conventional treatment options that provide durable remission are limited and median life expectancy is about six months, leaving a critical need for new therapies.^2,4

About Lisocabtagene Maraleucel (liso-cel)

Liso-cel is an investigational chimeric antigen receptor (CAR) T cell therapy designed to target CD19, which is a surface glycoprotein expressed during normal B-cell development and maintained following malignant transformation of B cells. Liso-cel aims to target CD19-expressing cells through a CAR construct that includes an anti-CD19 single-chain variable fragment (scFv) targeting domain for antigen specificity, a transmembrane domain, a 4-1BB costimulatory domain hypothesized to increase T cell proliferation and persistence, and a CD3-zeta T cell activation domain. The defined composition of CAR-positive viable T cells (consisting of CD8 and CD4 components) in liso-cel may reduce CAR T product variability; however, the clinical significance of defined composition is unknown.

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, that the outcome of pricing and reimbursement negotiations in individual countries in Europe may delay or limit the commercial potential of lisocabtagene maraleucel (liso-cel) for the indication described in this release, that such product candidate may not receive regulatory approval from the U.S. Food and Drug Administration for the indication described in this release in the currently anticipated timeline or at all, and whether such product candidate for such indication 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. Tilly H, Gomes da Silva M, Vitolo U, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26 Suppl 5:v116-v125.
2. Crump M, Neelapu SS, Farooq U et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017; 130(16): 1800-1808.
3. American Cancer Society. Types of B cell Lymphoma. Available at: https://www.cancer.org/cancer/non-hodgkin-lymphoma/about/b-cell-lymphoma.html . Accessed July 2020.
4. Raut LS, Chakrabarti PP. Management of relapsed-refractory diffuse large B cell lymphoma. South Asian J Can. 2014; 3(1): 66-70.