New findings from a Phase 3
multicenter, randomized head-to-head study comparing ustekinumab and
Enbrel(R) (etanercept) for the treatment of moderate to severe psoriasis
showed ustekinumab superior to Enbrel according to primary and major
secondary efficacy endpoints. The primary endpoint of the trial was the
percentage of participants achieving at least a 75 percent reduction in
psoriasis at week 12 as measured by the Psoriasis Area and Severity Index
(PASI 75). At week 12, after two subcutaneous injections at weeks 0 and 4,
68 percent and 74 percent of patients receiving ustekinumab 45 mg or
ustekinumab 90 mg, respectively, achieved a PASI 75 compared with 57
percent of patients receiving Enbrel 50 mg subcutaneous injections twice
weekly for twelve weeks (P = 0.012 for ustekinumab 45 mg; P < 0.001 for
ustekinumab 90 mg, each compared with Enbrel). Investigators presented
these data today at the 17th meeting of the European Academy of Dermatology
and Venereology (EADV) in Paris, France.
Ustekinumab is a new, investigational human monoclonal antibody with a
novel mechanism of action that targets the cytokines interleukin-12 (IL-12)
and interleukin-23 (IL-23), naturally occurring proteins that are important
in the body's regulation of immune responses and that are believed to play
a role in immune-mediated inflammatory disorders, including psoriasis.
"These findings reinforce the promise of ustekinumab as an infrequently
administered and highly effective biologic therapy for the treatment of
adults with moderate to severe psoriasis," said Bruce Strober, MD, PhD,
Department of Dermatology, New York University School of Medicine, New
York, New York, United States, and trial investigator. "Currently available
biologic therapies have greatly improved the treatment of psoriasis, yet
unmet needs in treatment remain for patients living with this chronic
inflammatory disease."
Investigators also reported that patients receiving ustekinumab
achieved higher marked improvements in psoriasis as assessed by PASI 90
improvement, or nearly complete clearance of psoriasis, and Physician
Global Assessment (PGA) scores compared with patients receiving Enbrel,
which were major secondary endpoints of the trial. At week 12, 36 percent
of patients receiving ustekinumab 45 mg and 45 percent of patients
receiving ustekinumab 90 mg achieved PASI 90 compared with 23 percent of
patients receiving Enbrel (P < 0.001 for each comparison versus Enbrel).
Moreover, a greater proportion of patients in the ustekinumab 45 mg and 90
mg treatment groups achieved a PGA score of "cleared" or "minimal" (65
percent and 71 percent, respectively) compared with patients in the Enbrel
treatment group (49 percent) (P < 0.001 for each comparison versus Enbrel).
Through week 12, the comparator-controlled portion of the study, the
percentages of study participants experiencing at least one adverse event
(AE) were comparable between the ustekinumab 45 mg group (66 percent), the
ustekinumab 90 mg group (68 percent) and the Enbrel 50 mg group (69
percent). Those patients experiencing at least one serious AE were reported
as follows: 1.9 percent and 1.2 percent of patients receiving 45 mg or 90
mg ustekinumab, respectively, compared with 1.2 percent of patients
receiving Enbrel. AEs leading to treatment discontinuation occurred in 1.9
percent and 1.2 percent of patients in the ustekinumab 45 mg and
ustekinumab 90mg groups, respectively, compared with 2.3 percent of
patients treated with Enbrel. Rates of specific adverse events were
generally comparable between treatment groups with the exception of
injection site erythema which was reported in 14.7 percent of subjects
treated with Enbrel versus 0.7 percent of subjects in the combined
ustekinumab groups, though this disparity may have been influenced by the
greater number of Enbrel injections required (up to 48 in the 12-week
study) compared with two ustekinumab injections.
"This study is significant for the dermatology community as it is the
first comparator trial of biologic therapies for psoriasis," said
Christopher Griffiths, MD, FRCP, School of Medicine, University of
Manchester, Manchester, UK, and lead trial investigator. "Treatment with
ustekinumab, which has a new mechanism of action that targets interleukins
12 and 23, has demonstrated significant clinical efficacy with infrequent
self-administered injections. Both are important considerations when
evaluating the burden of disease for many adult patients living with
moderate to severe psoriasis and who are candidates for a biologic
treatment."
About the ACCEPT Trial
The Phase 3, Multicenter, Randomized Study Evaluating the Efficacy and
Safety of Ustekinumab Compared to Etanercept in the Treatment of Subjects
with Moderate to Severe Plaque Psoriasis (ACCEPT) included 903 patients
with chronic plaque psoriasis (etanercept=347, ustekinumab 45 mg=209,
ustekinumab 90 mg=347). Patients were randomized to receive subcutaneously
administered ustekinumab or etanercept. Patients randomized to receive
ustekinumab received 45 mg or 90 mg doses at weeks 0 and 4. Patients in the
etanercept group received twice-weekly doses of 50 mg for 12 weeks. The
primary endpoint of the study was the proportion of patients who achieved
PASI 75 at week 12.
About Psoriasis
Psoriasis is a chronic, immune-mediated disease that results from the
overproduction of skin cells, resulting in their accumulation on the
surface of the skin, which causes red, scaly plaques that may itch and
bleed. It is estimated that approximately 7.5 million people in the United
States and 10 million Europeans are living with psoriasis and nearly
one-quarter of those people have cases that are considered moderate to
severe.
About Ustekinumab
Ustekinumab is a new, human monoclonal antibody in Phase 3 development
by Centocor, Inc. for the treatment of moderate to severe plaque psoriasis,
and is being investigated as an infrequently administered subcutaneous
injection. Ustekinumab is a novel biologic therapy that targets interleukin
12 (IL-12) and interleukin 23 (IL-23), naturally occurring proteins that
are important in regulating the immune system and that are believed to play
a role in immune-mediated inflammatory disorders.
On June 17, 2008, the FDA's Dermatologic and Ophthalmic Drugs Advisory
Committee (DODAC) unanimously recommended ustekinumab for approval. DODAC
is convened on request of the FDA to review and evaluate safety and
efficacy data of human drug products for use in the treatment of
dermatologic and ophthalmologic conditions. The committee provides
non-binding recommendations based on its evaluation; however, the FDA makes
the final decision on approval of the drug. Ustekinumab is also under
review by the European Medicines Agency (EMEA).
Centocor discovered ustekinumab and has exclusive marketing rights to
the product in the United States. Janssen-Cilag companies have exclusive
marketing rights in all countries outside of the United States.
About Centocor, Inc.
Centocor is harnessing the power of world-leading research and
biomanufacturing to deliver innovative biomedicines that transform
patients' lives. Centocor has already brought innovation to the treatment
of Crohn's disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic
arthritis, ulcerative colitis, pediatric Crohn's disease and psoriasis.
The world leader in monoclonal antibody production and technology,
Centocor has brought critical biologic therapies to patients suffering from
debilitating immune disorders.
About Janssen Cilag
Janssen-Cilag companies have a long track record in developing and
marketing treatments for central nervous system disorders, pain management,
infectious diseases, gastrointestinal disorders and oncology.
Enbrel is a registered trademark of Amgen and Wyeth Pharmaceuticals.
Centocor, Inc
centocor
View drug information on Enbrel.
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