Largest-Ever Phase III Early Rheumatoid Arthritis Study Shows REMICADE(R) Plus Methotrexate Superior to Standard of Care

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Largest-Ever Phase III Early Rheumatoid Arthritis Study Shows REMICADE®

Plus Methotrexate Superior to Standard of Care

ASPIRE Study for REMICADE Meets All Primary and Secondary Endpoints

First and Only Trial in Early RA to Demonstrate Superiority of an Anti-TNF

Regimen on Preventing Progression of Joint Destruction, Reducing Disability

and Increasing Overall Clinical Improvement Versus Methotrexate Alone

LISBON, PORTUGAL -- (MARKET WIRE) -- 06/19/2003 -- Results of a Phase III

clinical trial in early rheumatoid arthritis presented today at a major

international rheumatology meeting demonstrated that REMICADE® (infliximab)

plus methotrexate (³REMICADE regimen²) was superior to the standard therapy

of methotrexate in preventing progression of joint destruction, reducing

disability and increasing clinical improvement in patients with early

rheumatoid arthritis (RA). ASPIRE, (Active Controlled Study of Patients

Receiving Infliximab for Treatment of Rheumatoid Arthritis of Early Onset)

is the first and only study to date to report superiority in all three

endpoints in this patient population.

Results from this double-blind, active-controlled trial involving the

largest patient population ever studied in early RA were presented today at

the annual meeting of the European League Against Rheumatism (EULAR).

REMICADE is currently approved for use in patients who have had an

inadequate response to methotrexate alone. Based on the results of the

ASPIRE study, Centocor, a wholly owned subsidiary of & ,

intends to file for marketing approval with regulatory authorities for the

use of this REMICADE regimen in patients with early disease of moderate or

greater severity who have not previously demonstrated an inadequate response

to methotrexate therapy.

The ASPIRE study is the only clinical trial involving an anti-TNF regimen to

demonstrate superiority over high dose methotrexate in patients with early

disease. Patients in ASPIRE, on average, had been diagnosed with early RA

for seven months when entering the study.

³The ASPIRE findings represent a significant advance in the treatment of

RA,² said Professor f Smolen, ASPIRE co-primary investigator and

professor and chairman of the Department of Rheumatology, Lainz Hospital and

University of Vienna, Austria. ³This study demonstrates that early treatment

with REMICADE plus methotrexate is superior to methotrexate alone in

preventing the progression of RA. If left untreated, RA can lead to

crippling effects and possibly, disability. The ASPIRE data suggest the need

for a new approach to the treatment of rheumatoid arthritis -- early

intervention aimed at preventing the progression of joint destruction and

reducing disability.²

Previous studies have shown that a critical therapeutic window, ranging from

three months to one year from disease onset, exists in early rheumatoid

arthritis where irreversible joint damage and disability occur. (1), (2),

(3) Organizations such as EULAR and the American College of Rheumatology

(ACR) suggest that control of disease progression should start early before

joint destruction and disability occur. (4) Erosive disease occurs very

early in RA and has significant consequences on a patient¹s ability to

function as well as on disease costs. (4), (5) Joint destruction causes

swelling, intense pain, and disability within two years of diagnosis for

one-third of newly-diagnosed RA patients. (6) In the U.S., RA and rheumatic

diseases are cited as the number one expense for social security disability.

(7) More than 9.7 million people worldwide are diagnosed with RA. (8)

³In the ASPIRE trial, patients receiving methotrexate alone already had

significantly more radiographic damage at six months than those treated with

a combination of methotrexate plus REMICADE, " said E. St. Clair, MD,

ASPIRE co-primary investigator, Duke University Medical Center. " The early

treatment benefit seen among these patients provides further evidence that

aggressive therapy at the beginning of the disease is an effective strategy

to prevent the progression of joint damage. The results of the ASPIRE study

have the potential to change the way rheumatologists treat patients with

early disease. "

About ASPIRE

The ASPIRE study showed that patients treated with REMICADE plus

methotrexate at either tested dose prevented the progression of structural

damage while those treated with methotrexate alone continued to worsen.

Treatment with REMICADE plus methotrexate demonstrated a reduction in

disability for a majority of patients, and was superior to methotrexate

alone. The REMICADE regimen also provided a dramatic clinical response.

³The magnitude of clinical improvements seen in the ASPIRE trial have never

before been reported,² said Smolen. ³Nearly half of the REMICADE patients

reached an ACR 50 response, and more than one-third reached an ACR 70

response. Moreover, nearly one in seven patients achieved an ACR 90

response, a score which has never before been reported.²

ASPIRE was a randomized, double blind, active-controlled study involving

1049 patients enrolled in 125 centers in North America and Europe. Patients

in the ASPIRE study had an average of only seven months of disease duration

and more than 80 percent had evidence of erosive joint destruction. The

three co-primary clinical endpoints of ASPIRE were: prevention of structural

damage (joint destruction); prevention of disability; and sustained

improvement in signs and symptoms of disease at week 54.

Patients were randomized to receive 3 mg/kg of REMICADE plus methotrexate

(n=371), 6 mg/kg of REMICADE plus methotrexate (n=377), or placebo plus

methotrexate (n=291) at weeks 0, 2, and 6 and every 8 weeks thereafter

through week 46. The dose of methotrexate was rapidly escalated in 2.5 mg

increments every one to two weeks beginning with 7.5 mg/wk at week 0 and

reaching a dose of 15 mg/kg by week 5 and 20 mg/kg by week 8.

The most commonly reported adverse events were upper respiratory infection,

nausea and headache. Serious adverse events reported were similar to what

has been observed in controlled clinical trials and clinical experience with

REMICADE and described in the prescribing information. (See ³Important

Information² below).

Preventing Progression of Joint Destruction

Joint destruction was assessed by evaluating the change from baseline in the

modified Sharp score at week 54. Patients in the methotrexate-only arm,

despite escalation to a high dose, experienced significant progression of

joint destruction, with a mean change from baseline of 3.7 points, compared

to patients treated with the REMICADE regimen. Patients treated with both 3

mg/kg and 6 mg/kg of REMICADE in combination with methotrexate experienced

almost no progression, with mean change from baseline of 0.51 and 0.42

points respectively. The benefit seen in both REMICADE treatment arms was

statistically significant (p less than or equal to 0.001).

Reduction in Disability

Reduction in disability was measured using change in Health Assessment

Questionnaire (HAQ) scores over time from week 30 to week 54. The HAQ is a

validated measure of the degree of difficulty a patient has in accomplishing

everyday activities of daily living. Seventy-six percent of patients treated

with REMICADE plus methotrexate showed a clinically meaningful improvement

in functioning (reduction of HAQ scores of greater than or equal to 0.25),

versus 65 percent for patients on methotrexate alone. Patients in the 6

mg/kg REMICADE arm had a median improvement of .792 in HAQ scores and

patients in the 3 mg/kg REMICADE arm had a median improvement of .784

compared to a median improvement of .750 in the methotrexate-only arm (p

equals less than 0.001 and 0.030, respectively).

Clinical Improvement

Clinical improvement was measured by evaluating percent improvement in the

signs and symptoms of disease at week 54 as measured by ACR criterion

(ACRn). Overall the REMICADE regimen demonstrated a 68 percent incremental

improvement in clinical response versus that seen with methotrexate alone.

Specifically, patients treated with all doses of REMICADE had a 44 percent

overall clinical improvement, compared to a 26 percent improvement in

patients treated with methotrexate only. The superior clinical benefit seen

in patients treated with the REMICADE regimen was highly significant and was

evident at early time points in the trial. All results are statistically

significant with p values of < 0.001 for all infliximab groups.

Sixty-six percent of patients in the 6 mg/kg REMICADE arm and 62 percent of

patients in the 3 mg/kg arm achieved an ACR 20 score, compared to 54 percent

in the methotrexate-only arm (p=0.001 and 0.028, respectively). More

dramatic differences were observed in those patients achieving an ACR50 and

an ACR70 response. Forty-six percent and 50 percent of patients treated with

REMICADE 3 mg/kg and 6 mg/kg achieved an ACR50 response compared to only 32

percent of patients treated with methotrexate only, and 33 percent and 37

percent of patients treated with REMICADE 3 mg/kg and 6 mg/kg achieved an

ACR70 response compared to only 21 percent of patients treated with

methotrexate only. Additionally, one out of seven REMICADE-treated patients

achieved an ACR90 response compared to only six percent of methotrexate-only

treated patients. All results were statistically significant.

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

treatment, patients should discuss any heart condition with their doctor.

Patients should tell their doctor right away if they develop new or

worsening symptoms of heart failure (such as shortness of breath or swelling

of their feet).

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

sepsis. Some of these infections have been fatal. Patients should tell their

doctor if they have had recent or past exposure to people with TB. Their

doctor will evaluate them for TB and perform a skin test. If a patient has

latent (inactive) TB, his or her doctor should begin TB treatment before

starting REMICADE. If a patient is prone to or has a history of infections,

currently has one, or develops one while taking REMICADE, he or she should

tell his or her doctor right away. Patients should also tell their doctor if

they have lived in a region where histoplasmosis or coccidioidomycosis is

common, or if they have or have had a disease that affects the nervous

system, or if they experience any numbness, tingling, or visual

disturbances.

There are also reports of serious infusion reactions with hives, difficulty

breathing, and low blood pressure. In clinical studies, some people

experienced the following common side effects: upper respiratory infections,

headache, nausea, cough, sinusitis or mild reactions to the infusion such as

rash or itchy skin. Please read important information about REMICADE,

including full prescribing information, at www.remicade.com.

About REMICADE

REMICADE is a monoclonal antibody that specifically targets and irreversibly

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 RA,

Crohn¹s Disease (CD), a serious gastrointestinal disorder, and ankylosing

spondylitis, (AS), a chronic, progressive and debilitating inflammatory

disease, in addition to a wide range of Immune-Mediated Inflammatory

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

psoriasis and psoriatic arthritis.

REMICADE is the only anti-TNF biologic therapy that has received marketing

authorizations for the treatment of RA, CD and in the European Union, AS. In

most countries, REMICADE, in combination with methotrexate, is indicated for

the treatment of patients with moderate to severe rheumatoid arthritis.

REMICADE is the only biologic indicated for the treatment of patients with

moderate to severe, active Crohn¹s disease, including fistulizing Crohn¹s

disease.

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 and CD patients, REMICADE

is received 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. The safety and efficacy of

REMICADE is well established with over 10 years of clinical trial experience

and more than 400,000 patients treated worldwide -- more patients treated

than all other TNF inhibitors combined.

Important Information

Schering-Plough markets REMICADE in all countries outside of the United

States, except in Japan and parts of the Far East where Tanabe Seiyaku, Ltd.

markets the product. Centocor discovered REMICADE and has exclusive

marketing rights to the product in the United States.

SCHERING-PLOUGH DISCLOSURE NOTICE: The information in this press release

includes certain ³forward-looking² statements concerning, among other

things, the future prospects of the company and its products, which the

reader of this release should understand are subject to substantial risks

and uncertainties. The company¹s business prospects and the prospects of its

products may be adversely affected by general market and economic factors,

competitive product development, product availability, current and future

branded, generic and OTC competition, market acceptance of new products,

federal and state regulations and legislation, the regulatory review process

in the United States and foreign countries for new products and indications,

existing manufacturing issues and new manufacturing issues that may arise,

timing of trade buying, patent positions, litigation and investigations, and

instability or destruction in a geographic area important to the company due

to reasons such as war or SARS. For further details and a discussion of

these and other risks and uncertainties, see the company¹s Securities and

Exchange Commission filings, including the company¹s first quarter 2003 10-Q

filed with the Commission on May 13, 2003, and 8-Ks. Schering-Plough is a

research-based company engaged in the discovery, development, manufacturing

and marketing of pharmaceutical products worldwide.

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 Immune-Mediated Inflammatory

Disorders (I.M.I.D.), such as arthritis, inflammatory skin diseases and

cancer. Centocor¹s products, developed primarily through monoclonal antibody

technology, help physicians deliver innovative treatments to improve human

health and restore patients¹ quality of life. Centocor is a wholly owned

subsidiary of & , the worldwide manufacturer of healthcare

products.

JOHNSON & JOHNSON DISCLOSURE NOTICE: This press release contains

" forward-looking statements " as defined in the Private Securities Litigation

Reform Act of 1995. These statements are based on current expectations of

future events. If underlying assumptions prove inaccurate or unknown risks

or uncertainties materialize, actual results could vary materially from the

Company's expectations and projections. Risks and uncertainties include

general industry conditions and competition; economic conditions, such as

interest rate and currency exchange rate fluctuations; technological

advances and patents attained by competitors; challenges inherent in new

product development, including obtaining regulatory approvals; domestic and

foreign health care reforms and governmental laws and regulations; and

trends toward health care cost containment. A further list and description

of these risks, uncertainties and other factors can be found in Exhibit

99( of the Company's Annual Report on Form 10-K for the fiscal year ended

December 29, 2002. Copies of this Form 10-K are available online at

www.sec.gov or on request from the Company. The Company assumes no

obligation to update any forward-looking statements as a result of new

information or future events or developments.

References:

1. Egsmose C, Lund B, Borg G, et al. Patients with rheumatoid arthritis

benefit from early 2nd line therapy: 5 year follow up of a prospective

double blind placebo controlled study. J. Rheumatol. 1995;22:2208-2213.

2. Landewe RB, Boers M, Verhoeven AC, et al. COBRA combination therapy in

patients with early rheumatoid arthritis: long-term structural benefits of a

brief intervention. Arthritis Rheum. 2002;46:347-356.

3. O'Dell JR. Treating Rheumatoid Arthritis Early: A Window of Opportunity?

Arthritis & Rheumatism Feb 2002; 46(2):283-285.

4. American College of Rheumatology Subcommittee on Rheumatoid Arthritis.

Guidelines for the management of rheumatoid arthritis. 2002 update.

Arthritis Rheum. 2002;46(2):328-346.

5. Barrett EM, SCott DGI, Wiles NJ, Symmons DPM. The impact of rheumatoid

arthritis on employment status in the early years of disease: a UK

community-based study. Rheumatology. 2000;39:1403-1409.

6. van der Heijde DM. Joint erosions and patients with early rheumatoid

arthritis. Br J Rheumatol. 1995;34 (suppl 2):74-78.

7. Abdel-Nasser AM. Rasker JJ. Valkenburg HA. Epidemiological and clinical

aspects relating to the variability of rheumatoid arthritis. Seminars in

Arthritis & Rheumatism Oct 1997; 27(2):123-40.

8. Data on file at Schering-Plough