U.S. Food and Drug Administration Approves Orencia® (abatacept) in Combination with a Calcineurin Inhibitor and Methotrexate for the Prevention of Acute Graft Versus Host Disease (aGvHD)...

Rhea-AI Summary

Bristol Myers Squibb (NYSE:BMY) has announced that the U.S. Food and Drug Administration (FDA) has approved Orencia^® (abatacept) for preventing acute graft versus host disease (aGvHD) in patients receiving hematopoietic stem cell transplants. This marks the fourth FDA indication for Orencia, which is already established in treating several rheumatic diseases. The approval is particularly significant given the higher risk of aGvHD in racial and ethnic minority populations due to challenges in finding matched donors.

Positive

• Approval of Orencia for aGvHD adds a new indication, enhancing its market potential.
• Addresses a significant unmet medical need, particularly for minority populations.
• Strong clinical trial results indicating improved survival rates and aGvHD-free survival.

Negative

• None.

Orencia is the first and only FDA-approved therapy to help prevent this serious complication that impacts between 30-70% of hematopoietic stem cell transplant recipients¹   

Approval marks fourth indication for Orencia, an established treatment across three rheumatic diseases²

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE:BMY):

U.S. Food and Drug Administration Approves Orencia^® (abatacept) in Combination with a Calcineurin Inhibitor and Methotrexate for the Prevention of Acute Graft Versus Host Disease (aGvHD) in Patients Undergoing Hematopoietic Stem Cell Transplant from a Matched or 1 Allele-Mismatched Unrelated Donor

Bristol Myers Squibb (NYSE:BMY) today announced that Orencia^® (abatacept) was approved by the U.S. Food and Drug Administration (FDA) for the prophylaxis, or prevention, of acute graft versus host disease (aGvHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor (URD).²

“Orencia is the first FDA-approved therapy to prevent acute graft versus host disease following hematopoietic stem cell transplant, a potentially life-threatening complication that can pose a comparatively higher risk to racial and ethnic minority populations in the U.S. due to difficulty finding appropriately matched donors,”^2,3 said Tina Deignan, senior vice president, U.S. Immunology, Bristol Myers Squibb. “With this fourth indication for Orencia, Bristol Myers Squibb draws on its legacy and expertise in both immunology and hematology to deliver an important treatment option for patients in a disease with high unmet need.”^1,2

Allogeneic HSCT is a treatment for hematologic diseases that involves the infusion of hematopoietic stem cells, which include donor T-cells, a type of white blood cell that recognizes and destroys foreign invaders and damaged or cancerous cells in the recipient’s body. Acute graft versus host disease occurs when the donor T-cells recognize the patient’s healthy cells as foreign and start attacking healthy tissues and organs.¹

Orencia – a therapy that is also currently approved to treat adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, and moderate to severe polyarticular juvenile idiopathic arthritis in children 2 and older – binds to and modulates protein targets involved in costimulation, thus inhibiting T-cell activation.² The relationship of these biological response markers to the mechanisms by which Orencia exerts its clinical effects is unknown.

The concomitant use of Orencia with other immunosuppressives [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.² Orencia is associated with the following Warnings and Precautions: increased risk of infection with concomitant use with TNF antagonists, other biologic RA/PsA therapy, or JAK inhibitors; hypersensitivity; increased risk of serious infections; interactions with immunizations; increased risk of adverse events when used in patients with chronic obstructive pulmonary disease; immunosuppression; and cytomegalovirus (CMV) and Epstein-Barr virus (EBV) reactivation in aGvHD prophylaxis after HSCT.² Please see Important Safety Information below and U.S. Full Prescribing Information for additional details. The most common adverse events (≥10%) in rheumatoid arthritis are headache, upper respiratory tract infection, nasopharyngitis, and nausea. The most commonly reported adverse reactions in the prophylaxis of aGvHD with an incidence of at least 10% in Orencia-treated patients and at least 2% greater than placebo were anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia, and acute kidney injury.²

“In the GVHD-1 trial, abatacept demonstrated improved severe (grade III-IV) aGvHD-free survival in 7/8 mismatched unrelated donor transplant and associated mortality,”⁴ said Leslie Kean, M.D., director of the Stem Cell Transplantation Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. “The findings suggest abatacept could play an important role in preventing aGvHD in hematopoietic stem cell transplant. From these results, providers may also have more confidence in expanding the donor pool to include unrelated matched or 1 allele-mismatched donors for patients in need.”

This approval is based on results from the Phase 2 GVHD-1 trial, also known as ABA2, that evaluated Orencia when added to a regimen of a CNI (cyclosporine or tacrolimus) and MTX for prophylaxis of aGvHD in patients undergoing HSCT, and a clinical study known as GVHD-2 using data from the Center for International Blood and Marrow Transplant Research (CIBMTR).^2,4 GVHD-1 was a multicenter, two cohort trial (a double-blind, placebo controlled cohort and open-label, single-arm cohort) of patients age 6 years and older who underwent HSCT from a matched (n=142) or 1 allele-mismatched (n=43) URD.² GVHD-2 – a second clinical study using data from the CIBMTR – was also conducted to analyze outcomes of Orencia in combination with CNI and MTX (n=54) for aGvHD prophylaxis in comparison to that of recipients who received only CNI and MTX (n=162), in patients 6 years of age or older undergoing HSCT from a 1 allele-mismatched URD between 2011 and 2018.^2,4 Please see below for additional trial data.

“With Orencia’s approval as a preventive option for aGvHD following unrelated donor HSCT, we hope hematopoietic stem cell transplant becomes a more accessible option for more patients,”² explains Steven Devine, M.D., chief medical officer, NMDP/Be The Match, and associate scientific director, CIBMTR^®. “This may include patients of diverse ethnicities, who often have lower likelihoods of finding matched donors.”³

An abstract with the GVHD-2 data was presented at the American Society of Hematology Annual Meeting and Exposition in December 2021.

The FDA’s review was conducted under its Project Orbis initiative, which enabled concurrent and/or shared FDA review with the health authorities in Canada, Switzerland and as a pilot in Israel. Orencia is not approved for this indication in these countries.

About GVHD-1 (ABA2)

The GVHD-1 study (NCT01743131), also known as ABA2– “Abatacept Combined with a Calcineurin Inhibitor and Methotrexate for Graft versus Host Disease Prophylaxis: A Randomized Controlled Trial” – was a multicenter, two cohort, Phase 2 investigator sponsored trial conducted by Dr. Leslie Kean of Dana-Farber/Boston Children’s.⁴ The efficacy and safety of Orencia, in combination with a CNI and MTX, for the prophylaxis of aGvHD was evaluated in this trial in patients age 6 years and older who underwent HSCT from a matched or 1 allele-mismatched URD.^2,4

The two cohorts in GVHD-1 were 1) an open-label, single-arm study of patients who underwent a 7 of 8 HLA-matched HSCT (n=43) (“7/8” cohort), and 2) a randomized (1:1), double-blind, placebo-controlled study of patients who underwent an 8 of 8 HLA-matched HSCT who received Orencia (n=73) or placebo (n=69) in combination with a CNI and MTX (“8/8” cohort).² All subjects received a CNI, with dosing starting on Day -2 and continuing through at least Day 100 as tolerated, and MTX on Days 1, 3, 6 and 11 after transplant.⁴ Orencia-treated subjects received 10 mg/kg Orencia as an intravenous (IV) infusion over 60 minutes on Day -1 (the day before transplantation), followed by Days 5, 14 and 28 after transplantation.² In both cohorts, efficacy was established based on overall survival (OS) and grade II-IV aGvHD-free survival results assessed at Day 180 post-transplantation.² Orencia + CNI and MTX did not significantly improve grade III-IV aGvHD-free survival versus placebo + CNI and MTX at Day 180 post-transplantation.

In the 8/8 HLA-matched cohort, an estimated rate of grade III-IV aGvHD-free survival of 87% was observed for the Orencia IV + CNI + MTX group versus 75% for placebo + CNI + MTX (Hazard Ratio [HR] 0.55, 95% Confidence Interval [CI]: 0.26 to 1.18).² An estimated rate of grade II-IV aGvHD-free survival of 50% was observed for the Orencia IV + CNI + MTX group versus 32% for placebo + CNI + MTX (HR 0.54, 95% CI: 0.35 to 0.83).² aGvHD-free survival was measured from the date of transplantation until the onset of documented aGvHD or death by any cause up to Day 180 post-transplantation. The rate of estimated OS was 97% for the Orencia IV + CNI + MTX group versus 84% for placebo + CNI + MTX (HR 0.33, 95% CI: 0.12 to 0.93).² In an exploratory analysis of the 7/8 cohort of Orencia-treated patients (n=43), the rates of grade III-IV aGvHD-free survival, grade II-IV aGvHD-free survival, and OS at Day 180 post-transplantation were 95% (95% CI: 83% to 99%), 53% (95% CI: 38% to 67%), and 98% (95% CI: 85% to 100%), respectively.²

Serious adverse events reported in >5% of patients who received Orencia in combination with a CNI and MTX included pyrexia (20%), pneumonia (8%), acute kidney injury (7%), diarrhea (6%), hypoxia (5%), and nausea (5%).² Permanent discontinuation of Orencia occurred in two patients (1.7%) due to one case each of pneumonia and allergic reaction.²

The most frequent adverse events of all grades reported in ≥10% of patients with aGvHD who received Orencia with a difference of ≥2% for the 7/8 cohort, 8/8 cohort Orencia arm, and 8/8 cohort placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia (28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%, and 22%), pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney injury (9%, 15%, and 10%), and hypermagnesemia (5%, 18%, 10%).²

Incidence rates of grade III or IV adverse events were the same as incidence rates of all grades, with the exception of grade III or IV pyrexia in all arms (9% [7/8 cohort], 10% [8/8 cohort, Orencia arm], and 4% [8/8 cohort, placebo arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury in the 7/8 cohort Orencia arm (7%).² Clinically relevant adverse reactions in <10% of patients who received Orencia in combination with CNI and MTX in Study GVHD-1 included EBV reactivation.²

Use of Orencia for this indication in patients 2 to less than 6 years of age is supported by pharmacokinetic modeling and simulations of Orencia exposure.² The safety and effectiveness of Orencia have not been established in pediatric patients younger than 2 years of age for prophylaxis of aGvHD.²

About GVHD-2

GVHD-2 – a second clinical study using data from the CIBMTR – was conducted to analyze outcomes of Orencia in combination with CNI and MTX for aGvHD prophylaxis in comparison to that of recipients who received only CNI and MTX, in patients 6 years of age or older undergoing HSCT from a 1 allele-mismatched URD between 2011 and 2018.² The Orencia-treated group (n=54) included 42 patients from GVHD-1, in addition to 12 patients treated with Orencia outside of GVHD-1.² The comparator group (n=162) was randomly selected in a 3:1 ratio to the Orencia-treated group from the CIBMTR registry from patients who had not received Orencia during the study period. Analyses used propensity score matching and inverse probability of treatment weighting to help address the impact of selection bias. Efficacy was based on OS at Day 180 post-HSCT.² The OS rate at Day 180 in the Orencia in combination with CNI and MTX group was 98% (95% CI: 78 to 100) and the OS rate at Day 180 in the CNI and MTX group was 75% (95% CI: 67 to 82).² Please see Important Safety Information below, and U.S. Full Prescribing Information.

About Acute Graft Versus Host Disease and Impact on a Diverse Patient Population

Hematopoietic stem cell transplant (HSCT) is an effective treatment for hematological malignancies and other non-malignant hematological diseases, often representing the only option for cure.⁵ However, some of its benefit, especially in the case of unrelated donor transplantation, is offset by a high rate of transplant-related mortality stemming largely from severe acute graft versus host disease (aGvHD) and infection.⁶ Acute graft versus host disease after HSCT occurs when transplanted donor T-cells recognize antigenic differences between the donor and the recipient, and attack the recipient’s healthy tissue and organs.¹ This activation of T-cells can result in severe immune-mediated tissue damage to the host, with the skin, liver and gastrointestinal tract being the most common targets.¹ Acute graft versus host disease mediated damage to these vital organs has been associated with increased morbidity and death.¹

Acute graft versus host disease impacts up to 70 percent of patients who receive stem cell transplants, particularly those coming from unrelated and human leukocyte antigen (HLA)-mismatched donors.¹ This can be of particular concern with racial and ethnic minority patient populations following HSCT.^1,3 This may be due to several factors that impact overall outcome, including a lack of donor availability or access to matched HSCTs and related care.³

About ORENCIA

ORENCIA^® is a selective costimulation modulator that disrupts the continuous cycle of T-cell activation.

U.S. Indications/Usage and Important Safety Information for ORENCIA^® (abatacept)

Indications and Usage

Adult Rheumatoid Arthritis: ORENCIA^® (abatacept) is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).

Polyarticular Juvenile Idiopathic Arthritis: ORENCIA is indicated for the treatment of patients 2 years of age and older with moderately to severely active polyarticular juvenile idiopathic arthritis (pJIA).

Adult Psoriatic Arthritis: ORENCIA is indicated for the treatment of adult patients with active psoriatic arthritis (PsA).

Prophylaxis for Acute Graft versus Host Disease: ORENCIA is indicated for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor and methotrexate, in adults and pediatric patients 2 years of age or older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated-donor.

Limitations of Use: The concomitant use of ORENCIA with other potent immunosuppressants [e.g., biologic disease-modifying antirheumatic drugs (bDMARDS), Janus kinase (JAK) inhibitors] is not recommended.

Important Safety Information for ORENCIA^® (abatacept)

Increased Risk of Infection with Concomitant Use with TNF Antagonists, Other Biologic RA/PsA Therapy, or JAK Inhibitors: Concurrent therapy with ORENCIA and a TNF antagonist is not recommended. In controlled clinical trials, adult RA patients receiving concomitant intravenous ORENCIA and TNF antagonist therapy experienced more infections (63% vs 43%) and serious infections (4.4% vs 0.8%) compared to patients treated with only TNF antagonists, without an important enhancement of efficacy. Additionally, concomitant use of ORENCIA with other biologic RA/PsA therapy or JAK inhibitors is not recommended.

Hypersensitivity: There were 2 cases (<0.1%; n=2688) of anaphylaxis reactions in clinical trials with adult RA patients treated with intravenous ORENCIA. Other reactions potentially associated with drug hypersensitivity, such as hypotension, urticaria, and dyspnea, each occurred in <0.9% of patients. There was one case of a hypersensitivity reaction with ORENCIA in pJIA clinical trials (0.5%; n=190). In postmarketing experience, fatal anaphylaxis following the first infusion of ORENCIA and life-threatening cases of angioedema have been reported. Angioedema has occurred as early as after the first dose of ORENCIA, but also has occurred with subsequent doses. Angioedema reactions have occurred within hours of administration and in some instances had a delayed onset (i.e., days). Appropriate medical support measures for treating hypersensitivity reactions should be available for immediate use. If an anaphylactic or other serious allergic reaction occurs, administration of intravenous or subcutaneous ORENCIA should be stopped immediately and permanently discontinued, with appropriate therapy instituted.

Infections: Serious infections, including sepsis and pneumonia, were reported in 3% and 1.9% of RA patients treated with intravenous ORENCIA and placebo, respectively. Some of these infections have been fatal. Many of the serious infections have occurred in patients on concomitant immunosuppressive therapy which, in addition to their underlying disease, could further predispose them to infection. Caution should be exercised in patients with a history of infection or underlying conditions which may predispose them to infections. Treatment with ORENCIA should be discontinued if a patient develops a serious infection. Patients should be screened for tuberculosis and viral hepatitis in accordance with published guidelines, and if positive, treated according to standard medical practice prior to therapy with ORENCIA.

Immunizations: Prior to initiating ORENCIA in pediatric and adult patients, update vaccinations in accordance with current vaccination guidelines. Live vaccines should not be given concurrently with ORENCIA or within 3 months after discontinuation. ORENCIA may blunt the effectiveness of some immunizations. In addition, it is unknown if the immune response of an infant who was exposed in utero to abatacept and subsequently administered a live vaccine is impacted. Risks and benefits should be considered prior to vaccinating such infants.

Increased Risk of Adverse Reactions When Used in Patients with Chronic Obstructive Pulmonary Disease (COPD): In Study V, adult COPD patients treated with ORENCIA for RA developed adverse events more frequently than those treated with placebo, including COPD exacerbations, cough, rhonchi, and dyspnea. In the study, 97% of COPD patients treated with ORENCIA developed adverse events versus 88% treated with placebo. Respiratory disorders occurred more frequently in patients treated with ORENCIA compared to those on placebo (43% vs 24%, respectively), including COPD exacerbation, cough, rhonchi, and dyspnea. A greater percentage of patients treated with ORENCIA developed a serious adverse event compared to those on placebo (27% vs 6%), including COPD exacerbation [3 of 37 patients (8%)] and pneumonia [1 of 37 patients (3%)]. Use of ORENCIA in patients with COPD should be undertaken with caution, and such patients monitored for worsening of their respiratory status.

Immunosuppression: In clinical trials in adult RA patients, a higher rate of infections was seen in ORENCIA-treated patients compared to placebo-treated patients. The impact of treatment with ORENCIA on the development and course of malignancies is not fully understood. There have been reports of malignancies, including skin cancer in patients receiving ORENCIA. Periodic skin examinations are recommended for all ORENCIA-treated patients, particularly those with risk factors for skin cancer.

Cytomegalovirus (CMV) and Epstein-Barr Virus (EBV) Reactivation in aGVHD Prophylaxis after Hematopoietic Stem Cell Transplant (HSCT): Post-Transplant Lymphoproliferative Disorder (PTLD) occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 4 patients (3.4%) experienced PTLD. All the PTLD events were associated with Epstein-Barr virus (EBV) infection. The range of time to onset of the event was 49 to 89 days post-transplant. Monitor patients for EBV reactivation in accordance with institutional practices. Before administering Orencia, provide recommended prophylaxis for EBV infection and continue for 6 months post-transplantation to prevent EBV-associated PTLD. Cytomegalovirus (CMV) invasive disease occurred in patients who received ORENCIA for aGVHD prophylaxis during unrelated HSCT. Of 116 patients who received ORENCIA, 7% (n=8) experienced CMV invasive diseases up to day 225 post-transplant. The median time to onset of the event was 91 days post-transplant. CMV invasive diseases predominantly involved the gastrointestinal tract. Monitor patients for CMV infection/reactivation for 6 months post-transplant regardless of the results of donor and recipient pre-transplant CMV serology. Consider prophylaxis for CMV infection/reactivation during treatment and for six months following HSCT.

Blood Glucose Testing: ORENCIA for intravenous administration contains maltose, which may result in falsely elevated blood glucose readings on the day of infusion when using blood glucose monitors with test strips utilizing glucose dehydrogenase pyrroloquinoline quinone (GDH-PQQ). Consider using monitors and advising patients to use monitors that do not react with maltose, such as those based on glucose dehydrogenase nicotine adenine dinucleotide (GDH-NAD), glucose oxidase or glucose hexokinase test methods. ORENCIA for subcutaneous (SC) administration does not contain maltose; therefore, patients do not need to alter their glucose monitoring.

Pregnancy: There are no adequate and well-controlled studies of ORENCIA use in pregnant women and the data with ORENCIA use in pregnant women are insufficient to inform on drug-associated risk. A pregnancy registry has been established to monitor pregnancy outcomes in women exposed to ORENCIA during pregnancy. Healthcare professionals are encouraged to register patients by calling 1-877-311-8972.

Lactation: There is no information regarding the presence of abatacept in human milk, the effects on the breastfed infant, or the effects on milk production. However, abatacept was present in the milk of lactating rats dosed with abatacept.

Most Serious Adverse Reactions: In controlled clinical trials, adult RA patients experienced serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo). In the GVHD-1 study, serious adverse reactions reported in >5% of patients who received ORENCIA in combination with a calcineurin inhibitor and methotrexate and >2% higher than placebo included pyrexia (20%), pneumonia (8%), acute kidney injury (7%), diarrhea (6%), hypoxia (5%), and nausea (5%).

Malignancies: The overall frequency of malignancies was similar between adult RA patients treated with ORENCIA or placebo. However, more cases of lung cancer were observed in patients treated with ORENCIA (0.2%) than those on placebo (0%). A higher rate of lymphoma was seen compared to the general population; however, patients with RA, particularly those with highly active disease, are at a higher risk for the development of lymphoma. The potential role of ORENCIA in the development of malignancies in humans is unknown.

Most Frequent Adverse Events (≥10%): Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events in the adult RA clinical studies. Other events reported in ≥5% of pJIA patients were diarrhea, cough, pyrexia, and abdominal pain. In general, the adverse events in pediatric pJIA and adult PsA patients were similar in frequency and type to those seen in adult RA patients. The most frequent adverse reactions of all grades reported in ≥10% of patients with aGVHD who received ORENCIA with a difference of ≥2% for the 7/8 cohort, 8/8 cohort Orencia arm, and 8/8 cohort placebo arm, respectively, were anemia (56%, 69%, and 57%), CD4 lymphocytes decreased (14%, 14%, and 9%), hypertension (49%, 43%, and 38%), pyrexia (28%, 19%, and 20%), CMV reactivation/CMV infection (26%, 32%, and 22%), pneumonia (19%, 12%, and 10%), epistaxis (12%, 16%, and 10%), acute kidney injury (9%, 15%, and 10%), and hypermagnesemia (5%, 18%, 10%).

Incidence rates of grade 3 or 4 adverse reactions were the same as incidence rates of all grades, with the exception of grade 3 or 4 pyrexia in all arms (9% [7/8 cohort], 10% [8/8 cohort, Orencia arm], and 4% [8/8 cohort, placebo arm]), pneumonia in the 8/8 cohort placebo arm (9%) and acute kidney injury in the 7/8 cohort Orencia arm (7%). Clinically relevant adverse reactions in <10% of patients who received ORENCIA in combination with calcineurin inhibitor and methotrexate in Study GVHD-1 included EBV reactivation.

Note concerning ORENCIA administration options: ORENCIA may be administered as an intravenous infusion only for patients 6 years of age and older. PJIA patients may self-inject with ORENCIA or the patient’s caregiver may administer ORENCIA if both the healthcare practitioner and the parent/legal guardian determines it is appropriate. The ability of pediatric patients to self-inject with the autoinjector has not been tested. ORENCIA may only be administered as an intravenous (IV) infusion for the prophylaxis of aGVHD in patients undergoing HSCT. The safety and effectiveness of ORENCIA have not been established in pediatric patients younger than 2 years of age for prophylaxis of aGVHD.

Please click here for Full Prescribing Information.

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.

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, whether Orencia (abatacept), in combination with a calcineurin inhibitor and methotrexate, for the indication described in this release will be commercially successful, any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such combination treatment for such indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trials. 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, 2020, 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. Leukemia & Lymphoma Society. Graft-Versus Host Disease Fact Sheet No. 32. Updated 12/06/2017. https://www.lls.org/sites/default/files/National/USA/Pdf/Publications/FS32_GvHD_6.19_Update.pdf. Accessed September 6, 2021.
2. Orencia Prescribing Information. Orencia U.S. Product Information. Last updated: December 2021. Princeton, NJ: Bristol-Myers Squibb Company.
3. Majhail, NS et al. Racial disparities in hematopoietic cell transplantation in the United States. Bone Marrow Transplant. 2012 Nov;47(11): 10.1038/bmt.2011.214.
4. Bristol-Myers Squibb Company. Abatacept. Primary Clinical Study Report for Study IM101311: Abatacept Combined With a Calcineurin Inhibitor and Methotrexate for Graft Versus Host Disease Prophylaxis.
5. Khandelwal P, Yeh RF, Yu L, et al. Graft-versus-host Disease Prophylaxis With Abatacept Reduces Severe Acute Graft-versus-host Disease in Allogeneic Hematopoietic Stem Cell Transplant for Beta-thalassemia Major With Busulfan, Fludarabine, and Thiotepa. Transplantation. 2021;105(4):891-896. doi:10.1097/TP.0000000000003327
6. Ochs L, Shu XO, Miller J, et al. Late infections after allogeneic bone marrow transplantations: comparison of incidence in related and unrelated donor transplant recipients. Blood. 1995;86(10):3979-86.

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FAQ

What FDA approval did Bristol Myers Squibb receive for Orencia?

Bristol Myers Squibb received FDA approval for Orencia for the prevention of acute graft versus host disease in stem cell transplant patients.

What is the significance of Orencia's new indication for aGvHD?

This new indication addresses a major complication in stem cell transplants, particularly for patients with limited donor matches.

When was Orencia approved for acute graft versus host disease?

Orencia was approved for aGvHD by the FDA on December 13, 2021.

How does Orencia benefit patients undergoing stem cell transplants?

Orencia can reduce the risk of developing aGvHD, a serious complication that affects up to 70% of transplant recipients.

What types of patients can use Orencia following the FDA approval?

Orencia is indicated for adults and pediatric patients aged 2 years and older undergoing hematopoietic stem cell transplants.