New REMICADE Data Show Inhibition of Joint Destruction in Patients with Psoriatic Arthritis; Results from Radiographic Analysis Show Promise in Changing the Course of Disease Progression

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June 09, 2005 12:41 PM US Eastern Timezone

New REMICADE Data Show Inhibition of Joint Destruction in Patients with

Psoriatic Arthritis; Results from Radiographic Analysis Show Promise in

Changing the Course of Disease Progression

VIENNA, Austria--(BUSINESS WIRE)--June 9, 2005--New Phase 3 data show

that treatment with REMICADE® (infliximab) resulted in significantly

greater inhibition of structural damage compared to placebo in patients

with psoriatic arthritis. Radiographic analyses showed treatment with

REMICADE resulted in a mean change of -0.70 from baseline in structural

damage as measured using the van der Heijde-Sharp (vdH-S) scoring

method. With this method, higher scores indicate greater structural

damage while lower scores indicate less structural damage. These

24-week data, presented this week at the European League Against

Rheumatism (EULAR) Annual European Congress of Rheumatology, also

showed that REMICADE significantly reduced signs and symptoms of the

joints and skin in these patients.

" The inhibition of joint destruction is critical in the management and

treatment of psoriatic arthritis patients, " said van der

Heijde, MD, PhD, Professor of Rheumatology, University of Maastricht in

the Netherlands, one of the principal investigators in the trial.

" While it is unclear exactly how to interpret negative score changes,

the radiographic evidence clearly shows that more patients experienced

no worsening of joint destruction in the REMICADE group compared with

the placebo group. "

In the Induction and Maintenance Psoriatic Arthritis Clinical Trial 2

(IMPACT 2), REMICADE-treated patients had significantly less

progression of structural damage compared to patients receiving placebo

at week 24. Structural damage was measured using the vdH-S score, an

X-ray measure of changes in joint destruction, including joint erosion

and joint space narrowing. The mean (+/- standard deviation) change

from baseline in patients treated with REMICADE was a decrease of -0.70

(+/- 2.53) score, compared to an increase of 0.82 (+/- 2.62) score in

the placebo group (P less than 0.001). Results were similar when hands

(P less than 0.001), feet (P = 0.003), erosions (P less than 0.001) and

joint space narrowing (P = 0.013) were assessed.

Data presented from IMPACT 2 further demonstrated that treatment with

REMICADE resulted in significant improvement in both joint and skin

disease. At week 14, 58 percent of REMICADE-treated patients achieved

the primary efficacy outcome of at least 20 percent improvement from

baseline in arthritis symptoms as measured by the American College of

Rheumatology scoring criteria ACR 20, compared to 11 percent of

patients receiving placebo (P less than 0.001). Additionally, at week

14, 64 percent of patients receiving REMICADE therapy experienced at

least 75 percent improvement from baseline in the Psoriasis Area

Severity Index (PASI), compared to 2 percent of patients receiving

placebo (P less than 0.001). Similar results were seen at week 24.

REMICADE is a monoclonal antibody that specifically targets and binds

to tumor necrosis factor-alpha (TNF-alpha) on the cell membrane and in

the blood. Overproduction of TNF-alpha is believed to play a role in

rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis

and in a wide range of Immune-Mediated Inflammatory Disorders

(I.M.I.D.) in which REMICADE is currently being studied.

Centocor, Inc. plans to submit a supplemental Biologics License

Application (sBLA) with the United States Food and Drug Administration

(FDA) for inhibiting the progression of structural damage of active

arthritis in patients with psoriatic arthritis. REMICADE is approved in

the U.S. and Europe for the treatment of active psoriatic arthritis. In

May 2005, REMICADE was approved in the U.S. for reducing signs and

symptoms of active arthritis in patients with psoriatic arthritis. In

September 2004, REMICADE received European Union approval, in

combination with methotrexate, for the treatment of active and

progressive psoriatic arthritis in patients who have responded

inadequately to disease-modifying anti-rheumatic drugs (DMARDs).

About IMPACT 2

IMPACT 2 was a Phase 3 randomized, double-blind, placebo-controlled

study of 200 patients with active psoriatic arthritis (defined as

affecting at least five joints). The study evaluated the safety and

efficacy of REMICADE in patients who had an inadequate response to

DMARDs or nonsteroidal anti-inflammatory drugs (NSAIDs). Patients

received REMICADE (5mg/kg) or placebo at weeks 0, 2, 6 and every 8

weeks until week 22. In patients with greater than or equal to 3

percent body surface area (BSA) psoriasis involvement at baseline,

psoriasis activity was assessed using PASI at baseline and weeks 2, 6,

14 and 24.

Through 24 weeks, a similar proportion of patients experienced adverse

events (AEs) in each treatment group. No deaths, cases of tuberculosis

or other opportunistic infections or serious infusion reactions were

reported and serious infections were uncommon. Within 24 weeks of

treatment, one placebo-treated patient was diagnosed with basal cell

carcinoma. During the continued treatment with REMICADE beyond week 24,

one REMICADE patient was diagnosed with Hodgkin lymphoma. Laboratory

abnormalities were uncommon, with an elevation in liver function tests

being the most common abnormality. There were more patients with

serious AEs in the REMICADE group (8.7 percent) than in the placebo

group (6.2 percent). See " Important Safety Information " below.

About Psoriatic Arthritis

Psoriatic arthritis involves joint pain and swelling that can lead to

debilitation coupled with inflamed, scaly, red patches of psoriasis.

Symptoms may include stiffness and tenderness of the joints and

surrounding tissue, reduced range of motion, nail changes and redness

and pain of the eye. Joints of the hands, wrists, knees, ankles, feet,

lower back and neck are commonly affected. Approximately one million

Americans have psoriatic arthritis, and the disease affects both men

and women equally, most commonly between the ages of 30 and 50.

According to the Arthritis Research Campaign, approximately 1 in 50

people have psoriasis in the United Kingdom and about 1 in 14 of these

individuals will develop psoriatic arthritis.

About REMICADE

REMICADE is the global market leader among anti-tumor necrosis factor

alpha (TNF-alpha) therapies and the only agent approved for the

treatment of both rheumatoid arthritis (RA) and Crohn's disease (CD) in

North America, the European Union (EU) and Japan. In the EU and in the

U.S., REMICADE is approved for the treatment of active ankylosing

spondylitis (AS) and psoriatic arthritis.

In the EU, REMICADE is indicated for the treatment of severe, active CD

in patients who have not responded despite a full and adequate course

of therapy with a corticosteroid and an immunosuppressant; or who are

intolerant to or have medical contraindications for such therapies.

REMICADE also is indicated for the treatment of fistulizing, active CD

in patients who have not responded despite a full and adequate course

of therapy with conventional treatment (including antibiotics, drainage

and immunosuppressive therapy).

For RA patients in the EU, REMICADE, in combination with methotrexate,

is indicated for the reduction of signs and symptoms as well as the

improvement in physical function in patients with active disease when

the response to disease-modifying drugs, including methotrexate, has

been inadequate, and in patients with severe, active and progressive

disease not previously treated with methotrexate or other DMARDs. In

these patient populations, a reduction in the rate of the progression

of joint damage, as measured by X-ray, has been demonstrated.

In the EU, REMICADE is also indicated for treatment of AS in patients

who have severe axial symptoms, elevated serological markers of

inflammatory activity and who have responded inadequately to

conventional therapy.

In addition, REMICADE, in combination with methotrexate, is approved

for the treatment of active and progressive psoriatic arthritis in

patients who have responded inadequately to disease-modifying

anti-rheumatic drugs.

In the U.S., REMICADE, in combination with methotrexate, is indicated

for reducing signs and symptoms, inhibiting the progression of

structural damage, and improving physical function in patients with

moderately-to-severely active RA. REMICADE is the only biologic

indicated for the treatment of patients with moderately-to-severely

active CD who have had an inadequate response to conventional therapy.

REMICADE is also indicated for reducing the number of draining

enterocutaneous and rectovaginal fistulas and maintaining fistula

closure in patients with fistulizing CD. In December 2004, REMICADE was

approved for the treatment of active AS and in May 2005, REMICADE was

approved for reducing signs and symptoms of active arthritis in

patients with psoriatic arthritis in the U.S.

REMICADE is unique among available anti-TNF biologic therapies. Unlike

self-administered therapies that require patients to inject themselves

frequently, REMICADE is the only anti-TNF biologic administered

directly by caregivers in the clinic or office setting. In RA, CD, and

psoriatic arthritis, REMICADE is a two-hour infusion administered every

eight weeks, following a standard induction regimen that requires

treatment at weeks 0, 2 and 6. As a result, REMICADE patients may

require as few as six treatments each year. In AS, REMICADE is a

two-hour infusion (5 mg/kg) administered every six weeks, following a

standard induction regimen that requires treatment at weeks 0, 2 and 6.

The safety and efficacy of REMICADE have been well established in

clinical trials over the past 12 years and through commercial

experience with over a half a million patients treated worldwide.

Important Safety Information

Many people with heart failure should not take REMICADE; so prior to

treatment you should discuss any heart condition with your doctor. Tell

your doctor right away if you develop new or worsening symptoms of

heart failure (such as shortness of breath or swelling of your ankles

or feet).

There are reports of serious infections, including tuberculosis (TB),

sepsis and pneumonia. Some of these infections have been fatal. Tell

your doctor if you have had recent or past exposure to people with TB.

Your doctor will evaluate you for TB and perform a skin test. If you

have latent (inactive) TB, your doctor should begin TB treatment before

you start REMICADE. REMICADE can lower your ability to fight

infections, so if you are prone to or have a history of infections, or

develop any signs of an infection such as fever, fatigue, cough, or the

flu while taking REMICADE, tell your doctor right away.

Also tell your doctor if you have lived in a region where

histoplasmosis or coccidioidomycosis is common.

There have been rare cases of serious liver injury in people taking

REMICADE, some fatal. Contact your doctor immediately if you develop

symptoms such as jaundice (yellow skin and eyes), dark brown urine,

right-sided abdominal pain, fever, or severe fatigue.

Blood disorders have been reported, some fatal. Tell your doctor if you

develop possible signs of blood disorders such as persistent fever,

bruising, bleeding, or paleness while taking REMICADE. Nervous system

disorders have also been reported. Tell your doctor if you have or have

had a disease that affects the nervous system, or if you experience any

numbness, weakness, tingling, or visual disturbances while taking

REMICADE. Reports of lymphoma (a type of cancer) in patients on

REMICADE and other TNF blockers are rare but occur more often than in

the general population. Tell your doctor if you have or have had

cancer.

Serious infusion reactions have been reported with REMICADE, including

hives, difficulty breathing, and low blood pressure. Reactions have

occurred during or after infusions. In clinical studies, some people

experienced the following common side effects: respiratory infections

(that may include sinus infections and sore throat), coughing, and

stomach pain or mild reactions to infusion such as rash or itchy skin.

Please read important information about REMICADE, including full US

prescribing information, at www.remicade.com. For complete REMICADE EU

prescribing information, call Schering-Plough Corporation at +1

908-298-7616.

About Centocor

Centocor is a leading biopharmaceutical company that creates, acquires

and markets cost-effective therapies that yield long-term benefits for

patients and the healthcare community. The company is dedicated to the

research and development of treatments for a wide range of diseases

including cancer, infectious diseases, cardiovascular and metabolic

diseases and Immune-Mediated Inflammatory Disorders (I.M.I.D.), such as

arthritis and inflammatory skin diseases. Centocor's products,

developed primarily through monoclonal antibody technology, help

physicians deliver innovative treatments to improve human health and

restore patients' quality of life. Centocor is a wholly owned

subsidiary of & , the worldwide manufacturer of

healthcare products.

Centocor discovered REMICADE and has exclusive marketing rights to the

product in the United States. Schering-Plough Corporation has rights to

market REMICADE in all countries outside of the United States, except

in Japan, China (including Hong Kong), Taiwan and Indonesia, where

Tanabe Seiyaku, Ltd. markets the product.

About Schering-Plough

Schering-Plough is a global science-based health care company with

leading prescription, consumer and animal health products. Through

internal research and collaborations with partners, Schering-Plough

discovers, develops, manufactures and markets advanced drug therapies

to meet important medical needs. Schering-Plough's vision is to earn

the trust of the physicians, patients and customers served by its more

than 30,000 people around the world. The company is based in

Kenilworth, N.J., and its Web site is http://www.schering-plough.com.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press

release includes certain " forward-looking statements " within the

meaning of the Securities Litigation Reform Act of 1995, including the

company's strategy and the market for drugs to treat rheumatoid

arthritis. Forward-looking statements relate to expectations or

forecasts of future events and use words such as " will " and " plans. "

Actual results may vary materially from the forward-looking statements,

and there are no guarantees about the performance of Schering-Plough

stock or Schering-Plough's business. Schering-Plough does not assume

the obligation to update any forward-looking statement. Many factors

could cause actual results to differ from Schering-Plough's

forward-looking statements. These factors include uncertainties of the

regulatory approval and review process and difficulties in product

development. For further details about these and other factors that may

impact the forward-looking statements, see Schering-Plough's Securities

and Exchange Commission filings, including the company's first quarter

2005 10-Q and the 2004 annual report on Form 10-K.