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