Amgen (NASDAQ: AMGN) and Pfizer Inc. (NYSE: PFE) announced results of the second and final period of the PRESERVE trial. PRESERVE is a two-period multi-center trial in patients with moderately active rheumatoid arthritis (RA) who achieved Disease Activity Score (DAS) 28 low disease activity (LDA) or clinical remission on combination Enbrel® (etanercept) plus methotrexate (MTX) in Period one and were randomized to continue on ENBREL plus MTX or MTX alone in Period two. Results of Period two showed that the percentage of patients who maintained LDA or achieved clinical remission at week 88 was significantly higher in patients receiving ENBREL plus MTX than those on MTX alone. These results have been accepted in the late-breaker poster presentation at the 2011 American College of Rheumatology Annual Scientific Meeting in Chicago, from Nov. 5-9, 2011.
Patients with moderately active RA represent the largest RA population, yet they have not been widely studied as a distinct group in prospective clinical studies. The PRESERVE (A Prospective, Randomized Etanercept Study to Evaluate Reduced dose Etanercept + MTX v. full dose Etanercept + MTX v. MTX alone for efficacy and radiographic endpoints in a moderate RA population) study is the largest completed clinical trial of a biologic therapy in adults with moderately active RA, despite MTX treatment.
The PRESERVE trial met both its primary and conditional primary endpoints by demonstrating a statistically superior response in moderately active RA patients taking ENBREL 50mg weekly (QW) plus MTX or ENBREL 25mg QW plus MTX compared with those taking MTX monotherapy at 88 weeks. Specifically, after achieving LDA ( [DAS] 28 ≤3.2) at 36 weeks on ENBREL 50mg QW plus MTX, the percentage of patients maintaining LDA at week 88 was significantly higher in the ENBREL 50mg QW (82.6 percent, primary endpoint) and ENBREL 25mg QW (79.1 percent, conditional primary endpoint) treatment groups than the MTX- alone group (42.6 percent, P<0.0001 versus either ENBREL group). The U.S. Food and Drug Administration (FDA)- and the European Medicines Agency (EMA)- recommended dose for ENBREL for the treatment of moderate to severe RA is 50mg QW.
Additionally, for DAS 28 clinical remission (DAS28<2.6) HAQ ≤ 0.5,ACR20/50/70, and European League Against Rheumatism (EULAR) good response, the percentage of patients who achieved these secondary endpoints was significantly higher in the ENBREL treatment groups than the MTX-alone group (P<0.05).
"The medical community has recently questioned whether clinical remission or LDA could be sustained if a biologic agent is discontinued," said Josef S. Smolen, M.D., lead PRESERVE trial investigator and chairman of the Department of Rheumatology, Medical University of Vienna, Austria. "These data show that patients with moderately active disease who achieve LDA or clinical remission with ENBREL treatment may lose these clinical benefits if ENBREL is discontinued."
There were no new safety signals, and the safety profile from PRESERVE was consistent with that seen in previous ENBREL studies. Thirty-five subjects (5.8 percent) reported at least one serious adverse event (SAE) during Period two. The proportion of subjects with at least one SAE was similar among treatment groups (13 [6.4 percent], 7 [3.5 percent], and 15 [7.5 percent] in the full-dose, dose reduction, and MTX-only groups, respectively). No specific SAE was observed in more than two subjects. Two deaths, which were considered to be unrelated to the study medication, occurred in the ENBREL 50mg QW plus MTX group.
About PRESERVE
The 88-week PRESERVE study, the largest completed clinical trial of biologic therapy conducted in patients with moderately active RA (DAS28 >3.2 and ≤ 5.1), consisted of two study periods. During Period one, patients received open-label ENBREL 50mg QW plus MTX for 36 weeks. Those who responded to treatment (n=604; DAS28 ≤3.2 at week 36 and an average DAS28 ≤3.2 from week 12 through 36) were randomized to one of three treatment arms (ENBREL 50mg QW, ENBREL 25mg QW, or placebo) plus MTX, and followed for an additional 52 weeks. The FDA- and EMA- recommended dose for ENBREL for the treatment of moderate to severe RA is 50mg QW.
About Rheumatoid Arthritis
RA is a chronic inflammatory disease that affects approximately one percent of the adult population worldwide and can start at any age, but usually occurs between 40 and 70 years. RA can cause pain, stiffness, swelling and limitations in the motion and function of multiple joints. In RA, joint damage can significantly worsen over time, especially if left untreated. Joint damage may impair function, and potentially disable some patients.
About ENBREL
ENBREL is a soluble form of a fully human tumor necrosis factor (TNF) receptor with a clinical efficacy and safety profile established over 18 years of collective clinical experience. ENBREL was first approved in the U.S. in 1998 for moderate to severe rheumatoid arthritis and was later approved to treat children and adolescents with moderate to severe juvenile rheumatoid arthritis (now called juvenile idiopathic arthritis) in 1999. In 2004, ENBREL was approved in the U.S. to treat adult chronic moderate to severe plaque psoriasis. Prescription ENBREL is given by injection.
About Amgen
Amgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics have changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, bone disease and other serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives.
About Pfizer
At Pfizer, we apply science and our global resources to improve health and well-being at every stage of life. We strive to set the standard for quality, safety and value in the discovery, development and manufacturing of medicines for people and animals. Our diversified global health care portfolio includes human and animal biologic and small molecule medicines and vaccines, as well as nutritional products and many of the world's best-known consumer products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as the world's leading biopharmaceutical company, we also collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, Pfizer has worked to make a difference for all who rely on us.