Treatment with Enbrel® (etanercept) shows significant and sustained clinical benefits in Rheumatoid Arthritis (RA) patients with moderately active disease

Amgen (NASDAQ: AMGN) and Pfizer Inc. (NYSE: PFE) today 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 ENBREL Data at the American College of Rheumatology Annual Scientific Meeting

Amgen and Pfizer will also be presenting new analyses of data from several studies of ENBREL at the American College of Rheumatology Annual Scientific Meeting. Selected abstracts and presentations include:

• Treatment Outcomes Based on Methotrexate Dose Range in Patients with Rheumatoid Arthritis Receiving Etanercept Plus Methotrexate Versus Methotrexate Alone

Sunday, Nov. 6, PRESENTATION #: 441

• Baseline Predictors of Remission with Combination Etanercept-Methotrexate Therapy in Moderately Active Rheumatoid Arthritis: Interim Results of the PRESERVE Trial

Monday, Nov. 7, PRESENTATION #: 1216

• Discordance Between Patients and Physicians in Assessments of Global Disease Activity in Rheumatoid Arthritis: Agreeing to Disagree

Tuesday, Nov. 8, PRESENTATION #: 2512

• Higher Proportion of Rheumatoid Arthritis Patients Achieve Low Swollen and Tender Joint Counts and No Radiographic Progression with Etanercept Plus Methotrexate Versus Methotrexate Alone

Tuesday, Nov. 8, PRESENTATION #: 2239

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.

ENBREL indications in the U.S.:

• ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse and improving physical function in patients with moderate to severe rheumatoid arthritis. ENBREL can be taken with methotrexate or used alone.
• ENBREL is indicated for reducing signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in children ages 2 years and older.
• ENBREL is indicated for reducing signs and symptoms, keeping joint damage from getting worse and improving physical function in patients with psoriatic arthritis. ENBREL can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone.
• ENBREL is indicated for reducing signs and symptoms in patients with active ankylosing spondylitis.
• ENBREL is indicated for the treatment of adult patients (18 years or older) with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about ENBREL?

ENBREL is a medicine that affects your immune system. ENBREL can lower the ability of your immune system to fight infections. Serious infections have happened in patients taking ENBREL. These infections include tuberculosis (TB) and infections caused by viruses, fungi, or bacteria that have spread throughout the body. Some patients have died from these infections. Your doctor should test you for TB before you take ENBREL and monitor you closely for TB before, during, and after ENBREL treatment, even if you have tested negative for TB.

There have been some cases of unusual cancers reported in children and teenage patients who started using tumor necrosis factor (TNF) blockers before 18 years of age. Also, for children, teenagers, and adults taking TNF blockers, including ENBREL, the chances of getting lymphoma or other cancers may increase. Patients with RA or psoriasis may be more likely to get lymphoma.

Before starting ENBREL, tell your doctor if you:

• Have any existing medical conditions
• Are taking any medicines, including herbals
• Think you have, are being treated for, have signs of, or are prone to infection. You should not start taking ENBREL if you have any kind of infection, unless your doctor says it is okay
• Have any open cuts or sores
• Have diabetes, HIV, or a weak immune system
• Have TB or have been in close contact with someone who has had TB
• Were born in, lived in, or traveled to countries where there is more risk for getting TB. Ask your doctor if you are not sure
• Live, have lived in, or traveled to certain parts of the country (such as, the Ohio and Mississippi River valleys, or the Southwest) where there is a greater risk for certain kinds of fungal infections, such as histoplasmosis. These infections may develop or become more severe if you take ENBREL. If you don’t know if these infections are common in the areas you’ve been to, ask your doctor
• Have or have had hepatitis B
• Have or have had heart failure
• Develop symptoms such as persistent fever, bruising, bleeding, or paleness while taking ENBREL
• Use the medicine Kineret® (anakinra), Orencia®(abatacept), or Cytoxan® (cyclophosphamide)
• Are taking anti-diabetic medicines
• Have, have had, or develop a serious nervous disorder, seizures, any numbness or tingling, or a disease that affects your nervous system such as multiple sclerosis or Guillain-Barré syndrome
• Are scheduled to have surgery
• Have recently received or are scheduled for any vaccines. All vaccines should be brought up-to-date before starting ENBREL. Patients taking ENBREL should not receive live vaccines.
• Are allergic to rubber or latex
• Are pregnant, planning to become pregnant, or breastfeeding
• Have been around someone with chicken pox

What are the possible side effects of ENBREL?

ENBREL can cause serious side effects including: New infections or worsening of infections you already have; hepatitis B can become active if you already have had it; nervous system problems, such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes; blood problems (some fatal); new or worsening heart failure; new or worsening psoriasis; allergic reactions; autoimmune reactions, including a lupus-like syndrome and autoimmune hepatitis.

Common side effects include: Injection site reactions, upper respiratory infections (sinus infections), and headache.

These are not all the side effects with ENBREL. Tell your doctor about any side effect that bothers you or does not go away.

If you have any questions about this information, be sure to discuss them with your doctor. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

Please see Prescribing Information and Medication Guide at www.ENBREL.com