First pivotal study of BCMA-directed CAR T cell therapy in triple-class exposed relapsed and refractory multiple myeloma

Biologics License Application (BLA) for ide-cel was accepted by FDA for Priority Review, with a target action date of March 27, 2021

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Feb. 24, 2021-- Results from the pivotal Phase 2 KarMMa study evaluating the efficacy and safety of bluebird bio, Inc. (Nasdaq: BLUE) and Bristol Myers Squibb’s (NYSE: BMY) investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, idecabtagene vicleucel (ide-cel; bb2121), in adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, were published today in The New England Journal of Medicine.¹

The KarMMa study met its primary endpoint of overall response rate and key secondary endpoint of complete response rate. The data from the study demonstrates deep and durable responses with ide-cel treatment in triple-class exposed RRMM patients (n=128).

“The publication of KarMMa, the first pivotal study of a CAR T cell therapy in multiple myeloma, in The New England Journal of Medicine, underscores the importance of these data and the unprecedented outcomes observed in this triple-class exposed patient population, following a single infusion of ide-cel,” said David Davidson, M.D., chief medical officer, bluebird bio. “Together with our partners at Bristol Myers Squibb, we look forward to the prospect of bringing this first-in-class BCMA-directed CAR T therapy to patients.”

Clinically meaningful responses were reported in heavily pre-treated patients across all dose levels and in multiple high-risk subgroups, including those with high-risk cytogenetics, triple- or penta-refractory disease, high tumor burden at baseline, and extramedullary disease. Clinically meaningful improvement was also observed across measures for median duration of response, median progression-free survival and overall survival in treated patients.

In the KarMMa study, ide-cel demonstrated a safety profile consistent with known toxicities of CAR T cell therapies, regardless of dose level. The most frequently reported adverse events were cytopenia and cytokine release syndrome.

“Despite the progress made in the treatment of multiple myeloma over the past decade, long-term disease-free survival is uncommon and relapses are inevitable. Currently, the patients who have progressed through the three main classes of therapy do not have very effective therapeutic options and their outcome are often poor,” said Nikhil C. Munshi, M.D., lead author, Associate Director, The Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, Boston, Massachusetts. “The deep and durable responses observed in a large majority of patients in the KarMMa study published today in The New England Journal of Medicine demonstrate the potential of ide-cel to address a high unmet need for patients with heavily pre-treated and highly refractory multiple myeloma.”

The research included in this manuscript was first presented at the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program in May 2020. This is the second publication in The New England Journal of Medicine to report results of a study with ide-cel.

Ide-cel is not approved for any indication in any geography.

About Idecabtagene Vicleucel (ide-cel, bb2121)

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.

bluebird bio and Bristol Myers Squibb’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 high risk 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.

The European Medicines Agency (EMA) has validated the MAA for ide-cel and it is currently under review. The U.S. Food and Drug Administration accepted the ide-cel Biologics License Application for priority review on September 22, 2020 and set a Prescription Drug User Fee Act (PDUFA) goal date of March 27, 2021.

About KarMMa^2-4

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 the 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 bluebird bio, Inc.

bluebird bio is pioneering gene therapy with purpose. From our Cambridge, Mass., headquarters, we’re developing gene and cell therapies for severe genetic diseases and cancer, with the goal that people facing potentially fatal conditions with limited treatment options can live their lives fully. Beyond our labs, we’re working to positively disrupt the healthcare system to create access, transparency and education so that gene therapy can become available to all those who can benefit.

bluebird bio is a human company powered by human stories. We’re putting our care and expertise to work across a spectrum of disorders, including cerebral adrenoleukodystrophy, sickle cell disease, β-thalassemia and multiple myeloma, using gene and cell therapy technologies including gene addition, and (megaTAL-enabled) gene editing.

bluebird bio has additional nests in Seattle, Wash.; Durham, N.C.; and Zug, Switzerland. For more information, visit bluebirdbio.com.

Follow bluebird bio on social media: @bluebirdbio, LinkedIn, Instagram and YouTube.

bluebird bio is a trademark of bluebird bio, Inc.

bluebird bio 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 ide-cel. 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 that ide-cel may not receive the FDA’s approval for the indication described in this release in the currently anticipated timeline or at all, and, if approved, whether ide-cel will be commercially successful, that the positive results for ide-cel may not continue in additional clinical trials, that ide-cel may not receive marketing approval in the EU or in any jurisdictions outside of the US and the EU, and that the collaboration with Bristol Myers Squibb may not continue or be 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 bluebird bio’s business, particularly those identified in the risk factors discussion in bluebird bio’s Annual Report on Form 10-K, 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, bluebird bio 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. Munshi NC, Anderson LD, Shah N, et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2021 February 25;384:705-716.
2. Munshi NC, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): initial KarMMa results. ASCO 2020 Virtual Scientific Program. Abstract #39T850339T.
3. Raje N, Berdeja J, Lin Y, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019 May 2;380(18):1726-1737.
4. 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 February 2021.

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Source: bluebird bio, Inc.