The Phase 3 ACTIV-1 Immune Modulators study was sponsored by the National Institutes of Health as part of the ACTIV initiative

Orencia was one of two immune modulators that improved survival for people hospitalized with COVID-19

Safety profile of Orencia remained consistent, with no new safety signals reported

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced topline results from the Phase 3 Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV-1) Immune Modulators clinical trial, sponsored by the National Institutes of Health (NIH). The study evaluated the safety and efficacy of a single dose of immune modulators, including Orencia (abatacept) IV (10 mg/kg) versus placebo when given with standard of care to determine if modulating the immune system’s response could speed recovery and reduce death in adults hospitalized with moderate to severe COVID-19.

Treatment with Orencia versus placebo displayed a strong but not statistically significant improvement in the primary endpoint of time to recovery as measured by day of hospital discharge. Analyses of the secondary endpoints, which included mortality and clinical status, demonstrated Orencia reduced participants’ risk of death and improved their clinical status at 28 days after entering the study when compared with placebo. The risk of death was lower for participants who received Orencia at 11%, versus 15% for those who received placebo, and the odds of dying were 37.4% lower. The relative improvement in mortality was similar in both moderately and severely ill participants. People in the Orencia group had 34.2% better odds of clinical improvement than those in the placebo group. The safety profile of Orencia remained consistent, with no new safety signals reported in the study.

“With the continued need across the globe for treatment options to address the threat of COVID-19, we are proud of our involvement in the ACTIV-1 Immune Modulators clinical trial and our scientific research related to the virus. The devastating resurgences associated with circulating and emerging COVID variants underscore the need for additional therapeutic options for those who are hospitalized with COVID-19,” said Samit Hirawat, MD, chief medical officer, Bristol Myers Squibb. “We are pleased with the data demonstrating the risk of death was lower for participants who received Orencia and look forward to continued collaboration with the NIH to assess the data and potentially bring this treatment option to those in need.”

The full report on these data will be published in a peer-reviewed scientific journal. Given the positive findings from the topline data, Bristol Myers Squibb plans to discuss these data and potential next steps with the U.S. Food and Drug Administration.

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 (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