This has got to set a record for length in a PR. (Amgen just released 2 chest-pounding enbrel, and 1 kinaret, PRs. Let the marketing wars begin!)
Abbott Laboratories Presents HUMIRA(TM) (adalimumab), Also Known As D2E7, PIVOTAL PHASE III Data in Rheumatoid Arthritis (RA) Patients
Friday October 25, 6:30 pm ET
- Radiographic Data Presented on Structural Joint Damage Following One Year of Therapy -
ABBOTT PARK, Ill., Oct. 25 /PRNewswire/ -- Abbott Laboratories is presenting data this week from pivotal Phase III and ongoing clinical trials of HUMIRA(TM) (adalimumab, ?-da-lim-yoo-mab). HUMIRA, also known as D2E7, is Abbott Laboratories' investigational fully human monoclonal antibody, which is currently under review by the U.S. Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products (EMEA). Abbott announced it submitted applications to FDA and EMEA in April 2002. These studies included an evaluation of the safety and efficacy profiles for HUMIRA at a dose of 40 mg every other week in rheumatoid arthritis (RA), including inhibition of the progression of structural joint damage, maintenance of response after three years and impact on patients' quality of life.
-- In one pivotal Phase III study designed to evaluate inhibition of
radiographic progression of RA showing changes in X-rays, the primary
endpoints of the study were met. This 52-week study compared HUMIRA to
placebo, both in combination with methotrexate (MTX), on reduction in
modified Sharp X-ray score, which assesses changes in bone on X-rays.
The mean change for patients receiving HUMIRA 40 mg every other week
plus MTX was 0.1 compared to 2.7 for patients receiving placebo plus
MTX (see Table A).
-- In another long-term extension study, 64 percent of patients receiving
HUMIRA 40 mg every other week at three years achieved the American
College of Rheumatology (ACR) 20 response and nearly one in four
patients (24 percent) achieved an ACR 70 response. ACR scores
represent a percent improvement in tender and swollen joint count and
other relevant clinical measures (20 percent, 70 percent,
respectively).
-- In one 52-week study, patients' quality of life was measured using
patient assessment tests such as the Health Assessment Questionnaire
(HAQ) disability index. In this study, patients receiving HUMIRA 40 mg
every other week with MTX had a 0.59 mean change from baseline compared
to a 0.25 mean change from baseline for patients receiving placebo plus
MTX. The difference between HUMIRA and placebo was statistically
significant.
-- In the largest, controlled TNF-antagonist safety study of 636 patients
with RA, patients receiving HUMIRA plus the standard of care and those
receiving placebo and standard of care had similar rates of adverse
events, serious adverse events, infections and serious infections.
"The way rheumatologists address RA has changed dramatically over the past several years because of our understanding of how disease progression occurs and what it means to a patient," said Arthur Kavanaugh, M.D., professor of Medicine, director, Center for Innovative Therapy, University California San Diego, and a lead investigator in the HUMIRA X-ray trial. "The data being presented this week are compelling and give us a better understanding of the potential of HUMIRA."
Phase III Radiographic Outcomes
This pivotal Phase III trial was designed to evaluate radiographic outcomes, efficacy and safety over a 52-week period in patients with active RA who had inadequate response to MTX. The data are from 619 patients randomized to receive HUMIRA 40 mg every other week or 20 mg weekly, or placebo. All patients received stable doses of MTX. Patients enrolled in the study had an average disease duration of 11 years.
In addition to comparisons in the modified Sharp X-ray scores, 62 percent of patients receiving HUMIRA 40 mg every other week experienced no new bone erosions compared to 46 percent of those patients receiving placebo. There were also statistical differences in mean scores assessing bone erosion and joint space narrowing for the patients receiving HUMIRA 40 mg every other week versus those receiving placebo (see Table A).
"A reduction of RA signs and symptoms, combined with inhibition of joint destruction is the goal in treating patients," said Dr. Kavanaugh. "The X-ray images evaluated in this study provide an understanding of the impact HUMIRA 40 mg every other week may have on RA disease progression."
TABLE A.
Endpoint
HUMIRA 40 mg HUMIRA 20 mg Placebo
every other week weekly (n=200)
(n=207) (n=212)
Modified Sharp X-ray score
Mean baseline score 72.1 66.4 66.4
Mean change at week 52 0.1 0.8 2.7
Median change at week 52 0.0 0.0 1.0
Erosion score
Mean baseline score 41.4 36.7 37.2
Mean change at week 52 0.0 0.4 1.7
Joint space narrowing score
Mean baseline score 30.7 29.7 29.2
Mean change at week 52 0.1 0.5 1.1
The ability of HUMIRA to reduce the signs and symptoms of RA was also measured using the ACR 20, 50 and 70 criteria, which represent percent improvement in tender and swollen joint counts and other relevant clinical measures. Response rates in the trial at 52 weeks show differences between patients receiving HUMIRA 40 mg every other week and placebo (58.9 percent achieved ACR 20 versus 24.0 percent; 41.5 percent achieved ACR 50 versus 9.5 percent; and 23.2 percent achieved ACR 70 versus 4.5 percent).
In this study, the most common adverse events seen in patients receiving HUMIRA compared to placebo were injection site reactions (22.9 percent versus 23.5 percent), upper respiratory infection (19.6 percent versus 13.5 percent), rhinitis (16.9 percent versus 16.5 percent), and sinusitis (15.3 percent versus 13.0 percent). Withdrawals due to adverse events were 10 percent for HUMIRA versus. 6.5 percent for placebo.
Clinical Results After Three Years with HUMIRA
Follow-up data evaluating the long-term clinical efficacy and safety of HUMIRA in combination with MTX will also be presented from an open-label extension trial in which 79 percent of the 53 patients entering the study completed the three-year period.
ACR responses achieved in the study were reported in patients taking HUMIRA for three years: an ACR 50 response was achieved by 45 percent of patients at 36 months. An ACR 70 response was achieved by nearly one in four patients (24 percent) at 36 months. The majority of patients received HUMIRA every other week in this study. The rate of adverse events remained stable during the three-year evaluation period. Reasons for withdrawals were adverse events (6 patients), lack of efficacy (3 patients), death (myocardial infarction), withdrawal of consent and protocol violation.
"The data we are presenting at this meeting are a culmination of the extensive clinical development program that was put together for the HUMIRA regulatory applications in adult RA," said Steven Fischkoff, M.D., global project head for HUMIRA in RA.
Clinical Measures of Quality of Life
In addition to efficacy and safety data for HUMIRA, analyses from several studies using clinical measures of quality of life to evaluate the impact on patients will also be presented.
An analysis from the Phase III X-ray study also examined the impact of HUMIRA on patients' health-related quality of life (QOL). All patients in this study received concomitant MTX. QOL was measured by the HAQ disability index, Short Form 36-item Health Survey physician component summary scores (SF-36), and Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales.
-- The HAQ disability index is designed to capture patients' assessment of
activities of daily living such as grooming, dressing and walking. The
change for patients receiving HUMIRA 40 mg every other week was 0.59 at
52 weeks versus 0.25 for placebo.
-- The SF-36 is a questionnaire that measures patients' assessment of
general QOL measures. There are two component scores: physical
health, which tracks physical functioning, bodily pain and general
health, and mental health, which tracks vitality, social functioning
and emotional well-being. In the physical component summary score at
52 weeks in this study, patients receiving HUMIRA achieved a change of
8.5 (versus 3.1 for placebo), where the minimum clinically important
difference (MCID) is 2.5 to 5.
-- FACIT fatigue scores measure patients' assessment of factors related to
fatigue such as energy and effort required to complete daily tasks. At
52 weeks, patients receiving HUMIRA showed a mean change of 7.1 as
compared to a 3.3 change in patients on placebo, where 5 is the MCID.
In another of the pivotal Phase III studies, clinical measures assessed the ability of HUMIRA to improve physical and mental function and overall health-related QOL in patients. This study included 544 patients with long- standing RA. These patients had average disease duration of 11 years, 72 percent had failed three or more disease-modifying antirheumatic drugs (DMARDs) and 90 percent had failed MTX.
In this study at 26 weeks, patients taking HUMIRA 40 mg every other week compared to patients on placebo had the following changes: 12.9 versus 1.3 in physical function; 20.2 versus 7.2 in bodily pain; 16.1 versus 3.4 in vitality; and 10.3 versus 3.0 in mental health.
"RA can cause such debilitating effects on patients that it is important to track QOL measures in clinical trials in order to be able to understand the impact on the patients' lives," said Prof. L.B.A. van de Putte, M.D., University Hospital, Nijmegen, Netherlands. "The data in clinical trials with HUMIRA have been analyzed to assess changes in patients' ability to complete normal daily activities that are important to a person's independence such as getting dressed and walking up the stairs."
Phase III STAR Trial Results
Results from the Phase III STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis) trial, the largest, controlled safety study of a TNF-antagonist in RA, show that after 24 weeks of therapy the rates of adverse events, serious adverse events, infections, or serious infections were similar between HUMIRA and placebo when added to patients' pre-existing anti-rheumatic therapy. The trial included 636 patients and was designed to assess safety as a primary endpoint with a protocol that represented common clinical practice, in which it is common for physicians to prescribe a combination of DMARDs for patients with RA.
Patients in the study were taking up to four DMARDs when they were randomized to receive subcutaneous doses of either placebo or 40 mg of HUMIRA, every-other-week, in addition to their current DMARDs. The only adverse events that differed significantly between HUMIRA and placebo were injection site reactions, rash and back pain.
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