No Party Like CAR-Ts: Breyanzi, an Emerging CAR-T Therapy from Bristol Myers Squibb by Rafael Gacesa

Phase 1-2 Seamless Trial: TRANSCEND NHL 001

rafaelgacesa — 2024-11-24 19:55:55 UTC

The goal of TRANSCEND NHL 001 was to perform a combined phase 1 and 2 trial for Breyanzi to determine both the safety profile and efficacy and safety at different dose levels (1). The primary endpoints were adverse events, dose-limiting toxicities, and the objective response rate (1).

CLINICAL TRIALS

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For the sake of brevity, only trials which directly resulted in FDA approvals will be discussed.

Phase 3 Trial: TRANSFORM

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The goal of TRANSFORM was to compare the efficacy of Breyanzi to standard-of-care treatment for large B-cell lymphoma, which is high-dose chemotherapy, or autologous (unmodified) stem cell transplant (3). The primary endpoint was event-free survival (3).

Trial Design: TRANSCEND NHL 001

rafaelgacesa — 2024-11-24 20:08:21 UTC

This trial was a combined phase 1-2 trial. This combined smaller trial was allowed due the Breakthrough Drug and Regenerative Medicine Advanced Therapy FDA designations (1, 2). The Breakthrough Drug designation is given to drugs that treat a severe disease that display significant improvement in patient outcome compared to existing treatments (2). The Regenerative Medicine Advanced Therapy designation is given to Breakthrough Drugs which are biologics (2). These designations offer benefits such as smaller clinical trials and alternative trial designs (2).

The trial enrolled 344 adults with relapsed or refractory large B-cell lymphoma. All 344 patients underwent leukapheresis, 269 patients received Breyanzi, and 256 patients were included in the efficacy evaluable set, as shown in the study design figure (1).

Trials for Other Non-Hodgkin's Lymphomas (NHLs)

rafaelgacesa — 2024-11-24 20:13:20 UTC

There are 545,000 new cases of NHL annually, with 30% of these cases being LBCL (9). To expand their addressable market, BMS ran the TRANSCEND FL and TRANSCEND CLL 004 trials, which achieved third-line FDA approvals for FL and SLL/CLL (7, 8). This creates a potential market of 59% of NHL cases, improving Breyanzi's revenue prospects (9). This leads into the future outlook for Breyanzi, which is discussed in the next section.

rafaelgacesa — 2024-11-24 20:20:28 UTC

Results: TRANSCEND NHL 001

rafaelgacesa — 2024-11-26 02:30:02 UTC

The primary endpoint results are as follows: 9 (6%) dose-limiting toxicities occurred (1). The following grade 3 or worse adverse events occurred: 161 cases of neutropenia (60%), 101 cases of anemia (37%), 72 cases of thrombocytopenia (27%), 27 cases of neurological events (10%), 6 cases of CRS (2%) (1). CRS (at any grade) occurred in 80 patients (30%) (1). Adverse events occurred independent of dose level (1).

The objective response rate was 73% (186 patients) (1). The durable response duration (no disease progression) is shown in the figure on the left. Efficacy was found to be independent of dose level, leading to a recommended dose of 100MM cells (1).

Acknowledgements

rafaelgacesa — 2024-11-26 02:30:19 UTC

Sophia Mitonides: introduction section (writing, figure selection, poster design, citations) and relevant bibliography contributions.

Daniel Zhang: drug development section (writing, figure selection, poster design, citations) and relevant bibliography contributions.

Rafael Gacesa: clinical trials section (writing, figure selection, poster design, citations) and relevant bibliography contributions.

Andrew Nielsen: analysis & future outlook section (writing, figure selection, poster design, citations) and relevant bibliography contributions.

Trial Design: TRANSFORM

rafaelgacesa — 2024-11-26 02:31:41 UTC

232 adults with relapsed or refractory LBCL were enrolled in the trial, 184 of which were deemed eligible for reasons shown in the figure to the right (3). Patients were split into two groups of 92, one of which received a dose of 100MM cells of Breyanzi, and the other received standard-of-care (3). Of the standard-of-care group, 43 received high-dose chemotherapy, and 42 received autologous stem cell transplant (3). Note that both standard-of-care treatments included 3 rounds of regular-dose chemotherapy prior to their specific treatments (3). Patients in the Breyanzi group could also opt for a course of regular-dose chemotherapy while waiting for T-cell manufacturing depending on disease progress (3). More detail on the study design can be seen in the figure on the right.

rafaelgacesa — 2024-11-26 02:32:07 UTC

Results: TRANSFORM

rafaelgacesa — 2024-11-26 02:32:29 UTC

The primary endpoint, event-free survival (EFS), is displayed in the chart on the left. Overall, median EFS in the Breyanzi group was 14.8 months, compared to 5.7 months in the standard-of-care group (3).

Other key results from the TRANSFORM trial are shown in the figure below. Secondary endpoints include complete response (CR) rates, progression-free survival (PFS), and overall survival (OS) (3). As shown below, the Breyanzi group experienced improvements in all three secondary endpoints (3). Furthermore, the safety profile of Breyanzi was shown to be very similar to SOC based on adverse events (AEs), as shown below (3).

Strengths and Weaknesses: TRANSCEND NHL 001

rafaelgacesa — 2024-11-26 02:35:48 UTC

Strengths

The main strength of TRANSCEND NHL 001 was that it demonstrated that Breyanzi has a strong safety profile, with a remarkably low number of dose-limiting toxicities (6%) when compared to other CAR-T cell trials (1). For example, competitor Yescarta had a 14% incidence of dose-limiting toxicities (10).
Another strength of TRANSCEND NHL 001 is its large size, with 344 enrolled patients (1). This is a comparably massive trial for a phase 1-2 CAR-T cell trial; Yescarta's phase 1 trial had just 7 patients (10).
Lastly, a third strength of this trial was its ability to achieve third-line FDA approval for treatment of LBCL, meaning LBCL patients who had received 2 prior types of treatment would be eligible to receive Breyanzi (5). This expeditious approval was given do to the large amount of data collected due to the large size of the trial, the remarkable safety profile, and the FDA designations given to the drug.

Weaknesses

While the trial was large for a combined phase 1-2 trial, the 'seamless' combined design provided no time for follow-up with phase 1 trial patients before engaging in a phase 2 trial to achieve FDA approval. This means the trial produced less information about the long-term effects of the treatment.

Strengths and Weaknesses: TRANSFORM

rafaelgacesa — 2024-11-26 02:36:14 UTC

Strengths

The key strength of the TRANSFORM trial was the demonstrated improvement of the primary endpoint, event-free survival, when compared to standard-of-care (3). This near tripling of event-free survival time from 5.7 months to 14.8 months provides a convincing case for further approvals of Breyanzi's use (3).
A secondary strength of the TRANSFORM trial can be seen in the safety profile results. When comparing adverse-events, Breyanzi demonstrated a near-identical safety profile to standard-of-care, showing that the drug can greatly improve event-free survival without compromising on the safety and toxicity of the drug (3). This also provides safety data to corroborate the safety profile shown in the phase 1-2 TRANSCEND NHL 001 trial.
Lastly, because of the two listed strengths above, the TRANSFORM trial led to second-line approval of Breyanzi for treatment of LBCL (6). This is a massive improvement over the third-line approval achieved via TRANSCEND NHL 001, as it means Breyanzi can be given to a much wider range of patients.

Weaknesses

The key weakness of this trial was its size of just 232 enrolled patients (3). Typical phase 3 trials enroll a minimum of 300 patients, and they can be as large as 3,000 patients (11). This means TRANSFORM produced slightly less data than a typical phase 3 trial would, but the FDA still gave further approval; this is likely to due to the discussed designations.

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ANALYSIS & FUTURE OUTLOOK

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INTRODUCTION

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DRUG DEVELOPMENT

rafaelgacesa — 2024-11-26 03:30:10 UTC

References: Introduction

rafaelgacesa — 2024-11-26 03:39:30 UTC

1. About Us - Bristol myers squibb. BMS. (2024, November 27). https://www.bms.com/about-us.html

2. Yahoo! (2024, February 14). Beyond the balance sheet: What Swot reveals about Bristol-Myers Squibb Co (BMY). Yahoo! Finance. https://finance.yahoo.com/news/beyond-balance-sheet-swot-reveals-051222434.html?guccounter=1&guce_referrer=aHR0cHM6Ly93d3cuZ29vZ2xlLmNvbS8&guce_referrer_sig=AQAAAB3hyGL4a8TEbz8nVzRI3Fc-zymLhFh8ihxS2GKsAvsMn6IKM1be-GFiijoSMzM8AowZc3Kp872Q9tRji5RTJxifRYguv3w5mSjHqw68FG7dWOaBWr30mdZIWn7zbEPtlxH2GfQNP-W8mYBqhimxX9ETXfWu6YWIKl-w03h7FUAB

3. Research and development areas of Focus - Bristol Myers Squibb. BMS. (2024b, September 13). https://www.bms.com/researchers-and-partners/areas-of-focus.html

4. Achievements, Awards & Recognitions - bristol myers squibb. bms. (2024, June 5). https://www.bms.com/about-us/our-company/achievements.html

5. Bristol-Myers Squibb Company (BMY) stock historical prices & data - yahoo finance. Yahoo Finance. (n.d.). https://finance.yahoo.com/quote/BMY/history/

6. Bristol Myers Squibb - 52 Year stock price history: BMY. Macrotrends. (2024, November 28). https://www.macrotrends.net/stocks/charts/BMY/bristol-myers-squibb/stock-price-history

7. BMS . (2024, February 2). Bristol Myers Squibb - Bristol Myers Squibb reports fourth quarter and full-year financial results for 2023. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Reports-Fourth-Quarter-and-Full-Year-Financial-Results-for-2023/default.aspx

8. BMS Annual Report and accounts – 2020-2021 - BMS world mission. Our Response to COVID-19. (n.d.). https://www.bmsworldmission.org/product/bms-annual-report-and-accounts-2021/

9. Mikulic, M. (2024, May 22). Bristol-Myers Squibb top-products revenues 2021-2023. Statista. https://www.statista.com/statistics/266585/bristol-myers-squibbs-top-products-based-on-revenue/

10. Helfand, C. (2017, May 3). Pfizer, BMS’ eliquis takes J&J’s next-gen anticoagulant market-share crown. Fierce Pharma. https://www.fiercepharma.com/marketing/pfizer-bms-eliquis-takes-j-j-s-next-gen-anticoagulant-market-share-crown

11. Bloomberg. (2021, June 8). Celgene is paying $9 billion for Juno Therapeutics in blockbuster cancer drug deal. Fortune. https://fortune.com/2018/01/22/celgene-juno-deal/

12. Insights, G. M. (n.d.). Oncology Market Share & Size - 2032: Industry statistics report. Global Market Insights Inc. https://www.gminsights.com/industry-analysis/oncology-market

13. Jackson, M. (2024, February 2). Focus on execution pays off across Bristol’s new product portfolio. Insights. https://insights.citeline.com/SC149740/Focus-On-Execution-Pays-Off-Across-Bristols-New-Product-Portfolio/

14. Reviewing Bristol-Myers’ $90 billion acquisition of celgene. World of Dividends by Simply Safe Dividends. (2019, January 14). https://www.simplysafedividends.com/world-of-dividends/posts/1831-reviewing-bristol-myers-90-billion-acquisition-of-celgene

15. Bristol Myers Squibb - U.S. FDA approves Bristol Myers Squibb’s Breyanzi ® as the first and only car T cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). BMS. (2024b, March 4). https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx

16. Yahoo! (2024b, February 14). Bristol Myers wins dismissal of a $6.4 billion lawsuit over cancer drug delay. Yahoo! Finance. https://finance.yahoo.com/news/bristol-myers-wins-dismissal-lawsuit-225450955.html?guccounter=1

B-cell Lymphoma

danielzhang9876 — 2024-11-28 03:54:00 UTC

B-cell lymphoma is a form of Non-Hodgkin’s lymphoma, where white blood cells called B-cells become cancerous and begin to uncontrollably divide, leading to tumor growth and spread throughout the body. B-cell lymphomas comprise 85% of all Non-Hodgkin’s lymphoma cases, and there were projected to be 80,600 new diagnoses in the US in 2024 (1). With traditional treatment of chemotherapy or radiotherapy, the survival rate is quite high at 90%, however, this depends on time of treatment and aggressiveness of cancer, where advanced or severe cases may require more specialized treatment such as hematopoietic stem cell transplants, targeted B-cell agents, or immunotherapy (2). Notably, malignant B-cells express the surface antigen CD19 (3).

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Chimeric Antigen Receptor (CAR) T-Cells

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Our bodies have immune cells called T-cells, which are capable of killing cancer cells, however, they have many requirements for them to work. Typically, T-cells need to use their T-cell receptor (TCR) to detect an antigen that is presented on the major histocompatibility complex (MHC) of another cell, as well as receive costimulatory signaling to become activated, which leads to problems when the MHC or costimulatory molecules are gone in tumor microenvironments. If T-cells are instead equipped with a specifically engineered chimeric antigen receptor (CAR), they can simply detect surface antigens present on tumor cells, such as CD19, and provide both TCR and costimulatory signaling directly leading to T-cell activity and the efficient killing of tumor cells, in this case, malignant B-cells (4).

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Production and Delivery

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To produce and deliver CAR T-cell therapy, T-cells must first be isolated from cancer patients through a process called leukapheresis, where a machine isolates T-cells while returning other blood cells to the patient’s bloodstream. These T-cells can then be activated within proliferative environments with IL‐2 or anti‐CD3 antibodies. Then, using a lentiviral vector, the CAR gene can be delivered to the T-cells creating CAR T-cells. CAR T-cell populations must then be expanded to viable dose counts before intravenously reinfusing into patients and enhancing their antitumor response. It is important to note that patients must also undergo lymphodepletion chemotherapy, where their T-cell count is reduced to lower the activity of regulatory T-cells that may suppress CAR T-cell activity. Lymphodepletion also increases proliferative cytokine production of IL-7 and IL-15 which can promote CAR T-cell expansion within the body after infusion (4).

danielzhang9876 — 2024-11-28 04:23:21 UTC

Breyanzi: Preclinical Trial Results

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Breyanzi (lisocabtagene maraleucel) is a unique CAR T-cell therapy that uses a defined composition of CAR T-cells, where one dose of 60-120 million CAR T-cells aims to deliver a 1:1 ratio of naive CD4+ and central memory CD8+ CAR T-cells (6). CD4+ T-cells signal the immune response, while CD8+ T-cells mediate tumor killing (7). Naive T-cells lack previous exposure to antigens and circulate throughout the body, while central memory T-cells have had previous exposure and tend to patrol the blood and lymphatic system (8).

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Why Naive CD4+ CAR T-cells?

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Naive CD4+ CAR T-cells were chosen as they displayed the highest cytokine production in response to CD19-expressing cells in vitro among all CD4+ CAR T-cell types, as well as conferred the greatest survival benefit in mouse models of B-cell lymphoma at both low and high doses (9).

danielzhang9876 — 2024-11-28 05:21:35 UTC

Why Central Memory CD8+ T-cells?

danielzhang9876 — 2024-11-28 05:24:22 UTC

Central memory CD8+ CAR T-cells were chosen as they similarly conferred the greatest survival benefit in mouse models of B-cell lymphoma at both high and low doses among all other CD8+ CAR T-cell types (9).

Why the 1:1 Ratio?

danielzhang9876 — 2024-11-28 05:34:27 UTC

When combining both types of CAR T-cells in a 1:1 ratio, they were able to confer long-term and tumor-free survival in all treated mice with a very low dose (1 million CAR T-cells). Treatments with just one of the specific CAR T-cell types and treatments with non-specifically derived CAR T-cell types were unable to maintain a balanced ratio and could not replicate the protective effects.

Preclinical Trial Conclusion

danielzhang9876 — 2024-11-28 05:36:35 UTC

Thus, the 1:1 ratio of naive CD4+ and central memory CD8+ CAR T-cells was deemed as the most effective therapeutic design, and clinical trials with the composition soon followed.

danielzhang9876 — 2024-11-28 05:44:25 UTC

Insight into Breyanzi's success

andrewnielsen46 — 2024-11-28 16:40:45 UTC

What has Bristol Myers Squibb done to garner such success from Breyanzi?

Market analysis

andrewnielsen46 — 2024-11-28 16:44:21 UTC

How does the development of the CAR-T market tie into Breyanzi?

Competition

andrewnielsen46 — 2024-11-28 16:45:20 UTC

How does Breyanzi compare to their competitors? Further, what differentiates Breyanzi from their competitors?

Current and future market valuations

andrewnielsen46 — 2024-11-28 17:09:53 UTC

As recently as 2023, the US CAR-T market was valued at over 3 billion dollars, with an estimated valuation of over 35 billion dollars come 2032 (1). Further, a the global CAR-T therapy market is valued at over 88 billion dollars by 2023. These valuations are buttressed by a compound annual growth rate of 20.9%, exhibiting constant and steady growth (2).

Evidently, there is promising market for Breyanzi to exploit, but how does Breyanzi fit into the market?

andrewnielsen46 — 2024-11-28 17:14:27 UTC

Despite Breyanzi failing to control the largest share of the CAR-T market, they exhibit the highest compound annual growth rate of 30% (2). For reference, the compound annual growth rate of the market leaders, Yescarta, is a mere 9%. Further, it is important to note that Yescarta was approved by the FDA 4 years earlier than Breyanzi. Thus, Breyanzi has less market exposure time, yet boast a greater compound annual growth rate, delineating their immense potential.

Practical view of market growth (4)

andrewnielsen46 — 2024-11-28 17:46:29 UTC

Cancer still affects a large percentage of the global population and as of right now, there are no cures. Even though the incidence rate has declined, albeit not by a significant amount, cancer will still be a prevalent in the next 10 years. Thus, there is an ever-present need for CAR-T therapies as they represent a promising solution for cancer therapy.

Patient monitoring portal

andrewnielsen46 — 2024-11-28 17:57:35 UTC

A huge differentiator between Breyanzi and other CAR-T treatments is the establishment of a patient monitoring portal for those receiving treatment. Not only does this allow healthcare professionals to real-time monitor patients and potential presenting side-effects but it also gives the patients more connection to their treatment while undergoing such a tumultuous experience.

andrewnielsen46 — 2024-11-28 18:11:47 UTC

Seen above, Breyanzi is approved for third line treatments in four types of of B-cell lymphomas, compared to Yescarta which only has two indications for third line treatments. Thus, Breyanzi has a wider applicability than Yescarta in terms of third line treatment indications.

Safety profile

andrewnielsen46 — 2024-11-28 18:43:12 UTC

Breyanzi boasts quite a safe safety profile, which is measured by the onset of neurotoxicity or cytokine release syndrome (5). This is most likely due to their implementation of a 1:1 ratio of CD4+ and CD8+ cells.

Distinct treatments for Breyanzi

andrewnielsen46 — 2024-11-28 19:00:04 UTC

A reason as to why we see such a high ceiling for Breyanzi is they are the only approved CAR-T therapy for relapsed or refractory CLL or relapsed or refractory SLL. Breyanzi also exhibited substantially higher overall patient survival compared to chemotherapy treatments which has supported by a FDA approval for second-line treatment in relapsed or refractory large-B cell lymphoma. Not only does this support the promising prospect of Breyanzi as a treatment, but it also gives insight to some of the reasons as to why we have seen such recent success with Breyanzi. This is further seen in when looking at the CAR-T market and more specifically, Breyanzi's role in the market.

References: Drug Development

rafaelgacesa — 2024-11-28 19:36:20 UTC

B-cell Lymphoma. Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/22030-b-cell-lymphoma.
B-cell Lymphoma. Cincinnati Children's, https://www.cincinnatichildrens.org/health/b/b-cell-lymphoma.
Nadler LM, Anderson KC, Marti G, et al. B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes. J Immunol. 1983;131(1):244-250.
Makita S, Yoshimura K, Tobinai K. Clinical development of anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma. Cancer Sci. 2017;108(6):1109-1118.
Liscabtagene maraleucel. DrugBank, https://go.drugbank.com/drugs/DB16582.
Breyanzi Product Monograph. Bristol Myers Squibb, https://www.bms.com/assets/bms/ca/documents/productmonograph/BREYANZI_EN_PM.pdf.
Sun L, Su Y, Jiao A, Wang X, Zhang B. T cells in health and disease. Signal Transduct Target Ther. 2023;8(1):235.
Gray JI, Westerhof LM, MacLeod MKL. The roles of resident, central and effector memory CD4 T-cells in protective immunity following infection or vaccination. Immunology. Published online March 23, 2018. doi:10.1111/imm.12929
Sommermeyer D, Hudecek M, Kosasih PL, et al. Chimeric antigen receptor-modified T cells derived from defined CD8+ and CD4+ subsets confer superior antitumor reactivity in vivo. Leukemia. 2016;30(2):492-500.

References: Clinical Trials

rafaelgacesa — 2024-11-28 19:37:12 UTC

Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene Maraleucel for patients with relapsed or refractory large B-cell lymphomas (transcend NHL 001): A multicentre seamless design study. The Lancet. 2020;396, 839–852, doi: 10.1016/s0140-6736(20)31366-0.
Center for Biologics Evaluation and Research. OTP RMAT and BT Meetings. U.S. Food and Drug Administration, FDA, www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/meetings-regenerative-medicine-advanced-therapy-rmat-and-breakthrough-therapy-bt-designated-products.
Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene Maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (transform): Results from an interim analysis of an open-label, randomised, phase 3 trial. The Lancet, 2022;399, 2294–2308, doi: 10.1016/s0140-6736(22)00662-6.
Abramson JS, Solomon SR, Arnason J, et al. Lisocabtagene Maraleucel as second-line therapy for large B-cell lymphoma: Primary analysis of the Phase 3 Transform Study. Blood, 2023;141, 1675–1684, doi: 10.1182/blood.2022018730.
U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi (Lisocabtagene Maraleucel), a New Car T Cell Therapy for Adults with Relapsed or Refractory Large B-Cell Lymphoma. Bristol Myers Squibb, news.bms.com/news/details/2021/U.S.-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Breyanzi-lisocabtagene-maraleucel-a-New-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Large-B-cell-Lymphoma/default.aspx.
U.S. FDA Approves Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi® for Relapsed or Refractory Large B-cell Lymphoma After One Prior Therapy. Bristol Myers Squibb, https://news.bms.com/news/details/2022/US-FDA-Approves-Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzifor-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy/default.aspx
Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. Bristol Myers Squibb, https://news.bms.com/news/details/2024/Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
U.S. FDA Approves Bristol Myers Squibb’s Breyanzi ® as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Bristol Myers Squibb, https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx
NHL Subtypes. Leukemia & Lymphoma Society, www.lls.org/lymphoma/non-hodgkin-lymphoma/nhl-subtypes.
Locke FL, Neelapu SS, Bartlett NL, et al. Phase 1 Results of ZUMA-1: A Multicenter Study of KTE-C19 Anti-CD19 CAR T Cell Therapy in Refractory Aggressive Lymphoma. Molecular Therapy, 2017;25, 285-295, doi: 10.1016/j.ymthe.2016.10.020.
The Drug Development Process: Step 3: Clinical Research. U.S. Food and Drug Administration, FDA, https://www.fda.gov/patients/drug-development-process/step-3-clinical-research

References: Analysis & Future Outlook

rafaelgacesa — 2024-11-28 19:37:38 UTC

CAR T-Cell Therapy Market is Rising Rapidly at CAGR 29.8% by 2032. Biospace, https://www.biospace.com/car-t-cell-therapy-market-is-rising-rapidly-at-cagr-29-8-percent-by-2032
CAR T-cell Therapy Market Size, Share & Trends Analysis Report by Product (Abecma, Breyanzi), By Disease Indication (Lymphoma, Leukemia, Multiple Myeloma), By End-use, By Region, And Segment Forecasts, 2023 - 2030. Grand View Research, https://www.grandviewresearch.com/industry-analysis/car-t-cell-therapy-market-report
FDA approves CAR-T cell therapy to treat adults with certain types of large B-cell lymphoma. U.S. Food and Drug Administration, https://www.fda.gov/news-events/press-announcements/fda-approves-car-t-cell-therapy-treat-adults-certain-types-large-b-cell-lymphoma
Key Statistics for Non-Hodgkin Lymphoma. American Cancer Society, https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html
Weinstein B, Muresan B, Solano S, et al. Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. Innov Pharm. 2021;12(4), 18, doi: 10.24926/iip.v12i4.4345.
U.S. FDA Approves Bristol Myers Squibb’s Breyanzi ® as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). Bristol Myers Squibb, https://news.bms.com/news/details/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx

REFERENCES & ACKNOWLEDGEMENTS

rafaelgacesa — 2024-11-28 19:51:21 UTC

BMS and how they've become a leading company

sophiavmitonides — 2024-12-02 08:18:35 UTC

Bristol-Myers Squibb, also known as BMS, is a globally leading biopharmaceutical company that was first founded in 1858. (1) It has emerged as an industry leader because of its commitment to the discovery, development, and delivery of innovative medicines that help patients overcome serious diseases.(1,2) Some of BMS’ key strengths are its strong research and development (R&D) capabilities, strategic project and company acquisitions, and diversified product portfolio.(1,2) BMS blends the innovation and flexibility of a biotech company with the extensive resources and global reach of a well-established pharmaceutical firm.(3)

sophiavmitonides — 2024-12-02 08:21:10 UTC

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BMS has received wide recognition for their accomplishments in the field of biomedical health, accumulating many awards and titles as depicted above (4)

Market Analysis and Revenue

sophiavmitonides — 2024-12-02 09:10:51 UTC

The above figure depicts BMS stock price history (6)

Market Analysis and Revenue

sophiavmitonides — 2024-12-02 09:16:03 UTC

From January 2020 to August 2024, BMS showed resilience and growth in its stock performance. The stock did fluctuate due to market conditions and the COVID pandemic however it maintained a pretty strong position.(5) In 2020, the stock price recovered from a low of $38.83 to close at $53.55.(5,6) The next years saw growth, with significant gains in 2022, reaching an all-time high of $73.93.(6) Even with a decline in 2023, the stock rebounded in 2024, closing at $58.74, marking a 20.25% increase for the year.(6) In 2023, BMS reported $45B in revenue and is projected to bring in over $48B in revenue this year, which is a 6.67% increase in revenue in just one year. (7)

Further COVID-19 impacts

sophiavmitonides — 2024-12-02 09:22:57 UTC

During the COVID-19 pandemic, BMS took fast action to ensure its workforce's safety and provide a continuous supply of its medicines/treatments.(8) The company expanded patient support programs to help eligible unemployed patients in the U.S. who lost their health insurance by offering access to its products for free. BMS also adapted its clinical trials to ensure regulatory compliance and the integrity of its science.(8)

sophiavmitonides — 2024-12-02 09:46:10 UTC

The above figure depicts the revenue from the last three years for some of BMS' top-performing products. (9)

Major Products

sophiavmitonides — 2024-12-02 09:47:24 UTC

Much of BMS’ revenue is generated by their two most popular drugs. First, the anticoagulant Eliquis has proven to be one of the company’s most successful products by market share and, resulting in $12.2 billion in revenue in 2023. (9) Second, the anti-cancer monoclonal antibody Opdivo earned the company $9 billion in revenue in 2023. (9) These two drugs alone have helped push BMS to possess roughly 10% of the global oncology and anticoagulant drug market share relative to other corporations.(10) Additionally, Revlimid, used in adults who require blood transfusions due to myelodysplastic syndromes, brought in $6 billion in revenue in 2023, though this is a decrease from around $12.8 billion in 2021.(9)

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Acquisitions

sophiavmitonides — 2024-12-02 23:08:20 UTC

BMS' large fiscal size allows them to make strategic acquisitions in large markets with a need for drugs, leading to a diversified drug portfolio. Their largest acquisition, Celgene, had fortunately acquired a company called Juno a couple of years prior, giving them access to Juno's strong pipeline of cancer drugs, specifically CAR-T cell therapies (autologous chimeric antigen receptor T-cell therapy).(11) When BMS then acquired Celgene, it strengthened their oncology portfolio and capitalized on the growing oncology market, expected to surpass $400B in global spending by 2028.(12) This allowed BMS to become a leading oncology franchise in solid tumors and hematologic malignancies. In fact, BMS has actually been selling off major businesses to focus on higher-margin specialty drugs, like Breyanzi, which they obtained in their Celgene acquisition.(13)

sophiavmitonides — 2024-12-02 23:10:30 UTC

The above depicts BMS' major acquisitions from the past 18 years. (14)

Breyanzi

sophiavmitonides — 2024-12-02 23:31:53 UTC

Breyanzi is an CAR-T therapy recently approved in May 2024 for the treatment of four subtypes of relapsed/refractory B-cell lymphoma.(15) In just 2023 it brought in 296 million dollars, which is a notable increase from $182 million in 2022.(7) This product provides doctors and patients with increased accessibility to treatment and BMS heavily focused on increased production scaling efforts.(15)

sophiavmitonides — 2024-12-02 23:33:12 UTC

Missteps

sophiavmitonides — 2024-12-02 23:36:37 UTC

Most of BMS’s acquisitions and scientific projects typically are executed quite smoothly, however sometimes there are hiccups. Somewhat recently, BMS was accused of delaying Breyanzi’s development in order to avoid a payout to Celgene shareholders.(16) This payout was tied to timely FDA approvals, meaning that if the drug was developed within a certain amount of time, BMS would have to pay shareholders 6.4B dollars. A judge did end up dismissing the lawsuit, however the situation raised concerns about the company’s regulatory practices and transparency.(16) BMS has had similar legal issues such as the lawsuit related to the drug Plavix, which empahsized issues with jurisdiction and product liability.(8) BMS has also experienced financial volatility, partially because of significant one-time charges related to acquisitions.(2)