Princeton : Bristol-Myers Squibb Company announced the U.S. Food and Drug Administration (FDA) has approved ORENCIA for the treatment of adults with active Psoriatic Arthritis (PsA), a chronic, inflammatory disease that can affect both the skin and musculoskeletal system. ORENCIA is approved and available in both intravenous and subcutaneous (SC) injection formulations. ORENCIA should not be administered concomitantly with TNF antagonists, and is not recommended for use concomitantly with other biologic Rheumatoid Arthritis (RA) therapy, such as anakinra. This approval marks the third autoimmune disease indication for ORENCIA.
“This approval underscores the efficacy of ORENCIA in adult patients with active Psoriatic Arthritis, who have been in need of new treatments,” said Brian J. Gavin, Vice President, ORENCIA Development Lead at Bristol-Myers Squibb. “Helping to advance clinical understanding of autoimmune conditions is a key focus of our immunoscience research, and we’re proud to introduce ORENCIA, a selective T-cell co-stimulation modulator, as an additional treatment option for PsA.”
The co-stimulation blockade of ORENCIA inhibits T-cell activation and the resulting cascade of events that contribute to inflammation. T-cell activation is involved in the pathogenesis of PsA.
Psoriatic Arthritis can cause joint pain, stiffness and reduced range of motion, potentially affecting the ability to do everyday activities, such as getting dressed and tying shoes. In PsA, the immune system attacks healthy joints and skin.
“Psoriatic Arthritis takes a toll on patients and families over time,” said Randy Beranek, president and CEO, National Psoriasis Foundation. “We welcome the introduction of an additional treatment option for adults with active Psoriatic Arthritis, because we believe advancements, along with further research, education and support services, are critical to helping improve the lives of those impacted.”
The approval was based on results from two randomized, double-blind, placebo-controlled trials in which ORENCIA improved (or reduced) disease activity in both TNF-naive and exposed patients with high disease activity, high tender and swollen joints, and a disease duration of more than seven years.
ORENCIA PsA IV and SC Studies Demonstrated Improved Disease Response
The efficacy of ORENCIA was assessed in two randomized, double-blind, placebo-controlled studies (Studies PsA-I and PsA-II) in 594 adult patients with disease duration more than seven years. Patients had active Psoriatic Arthritis (≥ 3 swollen joints and ≥ 3 tender joints) despite prior treatment with DMARD therapy and had one qualifying psoriatic skin lesion of at least 2 cm in diameter. In PsA-I and PsA-II, 37% and 61% of patients, respectively, were treated with TNF inhibitors (TNFi) previously.1 The primary endpoint for both PsA-I and PsA-II was the proportion of patients achieving ACR 20 response at Week 24 (Day 169).
In PsA-I, a dose-ranging study, 170 patients received study drug IV at Days 1, 15, 29, and then every 28 days thereafter in a double-blind manner for 24 weeks, followed by open-label ORENCIA every 28 days. Patients were randomized to receive placebo or ORENCIA 3 mg/kg, 10 mg/kg (weight range-based dosing: 500 mg for patients weighing less than 60 kg, 750 mg for patients weighing 60 to 100 kg, and 1000 mg for patients weighing greater than 100 kg), or two doses of 30 mg/kg followed by weight range-based dosing of 10 mg/kg without escape for 24 weeks. Patients were allowed to receive stable doses of concomitant methotrexate, low dose corticosteroids (equivalent to ≤ 10 mg of prednisone) and/or NSAIDs during the trial. At enrollment, approximately 60% of patients were receiving methotrexate.
In PsA-II, 424 patients were randomized 1:1 to receive weekly doses of SC placebo or ORENCIA 125 mg SC without a loading dose for 24 weeks, followed by open-label ORENCIA 125 mg SC weekly. Patients were allowed to receive stable doses of concomitant methotrexate, sulfasalazine, leflunomide, hydroxychloroquine, low dose corticosteroids (equivalent to ≤ 10 mg of prednisone) and/or NSAIDs during the trial. At randomization, 60.4% of patients were receiving methotrexate.
A higher proportion of patients treated with ORENCIA 10 mg/kg IV or 125 mg SC achieved an ACR20 response at Week 24 compared to placebo, 47.5% versus 19.0% and 39.4% versus 22.3% (p< 0.05), respectively. Responses were seen regardless of prior anti-TNFi treatment and regardless of concomitant non-biologic DMARD treatment. Improvements in enthesitis and dactylitis were seen with ORENCIA treatment at Week 24 in both IV and SC.
There was a higher proportion of ORENCIA IV patients with at least a 0.30 decrease from baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) score at Week 24, with an estimated difference for ORENCIA 10 mg/kg (weight range-based dosing as described above) (45.0%) vs. placebo (19.0%) of 26.1 (95% confidence interval: 6.8, 45.5). The proportion of ORENCIA SC patients with at least a 0.35 decrease from baseline in HAQ-DI on ORENCIA was 31%, as compared to 24% on placebo (estimated difference: 7%; 95% confidence interval: -1%, 16%).1 There was a higher adjusted mean change from baseline in HAQ-DI on ORENCIA SC (-0.33) vs. placebo (-0.20) at Week 24, with an estimated difference of -0.13 (95% confidence interval: -0.25, -0.01).
The safety profile of ORENCIA was comparable between studies PsA-I and PsA-II and consistent with the safety profile in RA. The most serious adverse reactions reported in studies of adult RA patients were serious infections (3% ORENCIA vs 1.9% placebo) and malignancies (1.3% ORENCIA vs 1.1% placebo). Headache, upper respiratory tract infection, nasopharyngitis, and nausea were the most commonly reported adverse events (≥ 10%) in the adult RA clinical studies. In PsA-II, the most common adverse reactions (≥ 5%) were nasopharyngitis, upper respiratory tract infection, and bronchitis.
“It can be difficult to treat active Psoriatic Arthritis patients because the disease course is unpredictable, and patients are often treated with a variety of medications such as classic DMARDs and TNFs over time. Furthermore, once they have been treated, it may be more difficult to obtain an adequate efficacy response,” said Philip Mease, M.D., Clinical Professor at the University of Washington School of Medicine and Director of the Rheumatology Clinical Research Division of Swedish Medical Center. “The data that formed the basis of this approval demonstrate that ORENCIA offers an additional treatment option for patients with active Psoriatic Arthritis who have already tried a TNF inhibitor, as well as those who have not.”