|[March 22, 2014]
Pfizer Announces Detailed Results of OPT Compare Phase 3 Study of Tofacitinib 5 mg and 10 mg Twice Daily Compared to High-Dose ENBREL® in Adults with Moderate-to-Severe Chronic Plaque Psoriasis
NEW YORK --(Business Wire)--
Pfizer Inc. (NYSE:PFE) announced today detailed results from OPT Compare
(A3921080), a Phase 3 study of tofacitinib, the first in a new class of
treatment, oral Janus kinase (JAK) inhibitors, the safety and efficacy
of which are being investigated for the treatment of adults with
moderate-to-severe chronic plaque psoriasis. Top-line results from OPT
Compare were previously announced in October 2013. This is the first of
five studies from the Phase 3 Oral treatment Psoriasis Trial (OPT)
Program, one of the largest global clinical trial programs in
moderate-to-severe chronic plaque psoriasis to date. The results of OPT
Compare showed that in a step-down procedure design, tofacitinib 10 mg
twice daily (BID) was non-inferior to high-dose ENBREL®
(etanercept) 50 mg twice weekly (BIW), and tofacitinib 5 mg twice daily
did not meet the non-inferiority criteria compared to high-dose ENBREL.
No new safety signals for tofacitinib were observed in the OPT Compare
study. Detailed results of this study are being presented as an oral
presentation during the Latest in Dermatology Research Symposium at the
72nd American Academy of Dermatology (AAD) Annual Meeting held in
Denver, at 9:45 a.m. MDT today.
"We are pleased to present the detailed results of OPT Compare, the
first Phase 3 trial showing non-inferiority of an oral small molecule,
tofacitinib, versus an injected biologic agent, ENBREL, in psoriasis.
The results demonstrated that tofacitinib 10 mg twice daily had similar
efficacy to high-dose ENBREL 50 mg twice weekly," said lead author Hervé
Bachelez, M.D., Ph.D., Sorbonne Paris Cité Université Paris Diderot,
Department of Dermatology, APHP Hôpital Saint-Louis, Paris, France.
OPT Compare is a 12-week, non-inferiority study comparing the efficacy
and safety of tofacitinib 5 mg and 10 mg BID to high-dose ENBREL 50 mg
BIW, the approved starting dose for ENBREL for the first 12 weeks, and
placebo for the treatment of adult patients with moderate-to-severe
chronic plaque psoriasis. The results of the study showed that
tofacitinib 10 mg BID was non-inferior to high-dose ENBREL 50 mg BIW as
measured by Psoriasis Area and Severity Index (PASI) 75 response and
Physician's Global Assessment (PGA) response. The proportion of patients
that achieved a PASI75 response at week 12 was: tofacitinib 10 mg BID:
63.6 percent; ENBREL 50 mg BIW: 58.8 percent; tofacitinib 5 mg BID: 39.5
percent; placebo: 5.6 percent. The proportion of patients that achieved
"clear" or "almost clear" in PGA at week 12 were: tofacitinib 10 mg BID:
68.2 percent; ENBREL 50 mg BIW: 66.3 percent; tofacitinib 5 mg BID: 47.1
percent; placebo: 15.0 percent. Tofacitinib 5 mg BID did not meet the
non-inferiority criterion of 15 percent difference compared to high-dose
ENBREL as measured by PASI75.
The efficacy and safety profile of tofacitinib in this study was
expected based on what was seen in the Phase 2 clinical trial and dose
modeling. Rates of selected safety events of special interest in the
study patient population, including serious infections, herpes zoster,
non-melanoma skin cancer and cardiovascular events, were below 1 percent
and similar for all active treatment groups (both tofacitinib arms and
the ENBREL arm). The most frequent adverse events across active
treatment groups were infections (most commonly nasopharyngitis and
upper respiratory tract infections). Injection site reactions were more
frequent among patients receiving active ENBREL treatment compared with
the tofacitinib and placebo arms, whereas increases in cholesterol and
creatine phosphokinase were more common in tofacitinib recipients.
The detailed OPT Compare study results mark the completion of the first
Phase 3 trial for tofacitinib in psoriasis. Top-line results for the
second completed study, OPT Retreatment (A3921111), were previously
announced in October 2013, and detailed results will be presented at a
future scientific meeting. Top-line results from two of the three
remaining trials in the Phase 3 Oral treatment Psoriasis Trial (OPT)
Program, the OPT Pivotal 1 and OPT Pivotal 2 trials (A3921078 and
A3921079), are anticipated in the second quarter of 2014, and these four
studies, in addition to a long-term extension study, will form the
planned psoriasis submission package to regulatory authorities.
About OPT Compare (A3921080)
OPT Compare was a Phase 3 randomized, double-blind, double-dummy,
placebo-controlled 12-week non-inferiority study comparing the efficacy
and safety of tofacitinib 5 mg and 10 mg BID to high-dose ENBREL
(etanercept) 50 mg BIW and placebo (oral tablet and subcutaneous
injection) for the treatment of adult patients with moderate-to-severe
chronic plaque psoriasis who had an inadequate response to, intolerance
to, or contraindication to conventional systemic therapy. Patients that
previously failed treatment with a tumor necrosis factor (TNF) inhibitor
were excluded from this study. There were 1,106 patients enrolled in
this study in 23 countries outside of the U.S. and Canada (three Latin
American countries, three in Asia, 16 in Europe, and one in the Middle
About the OPT Clinical Trial Program
The Phase 3 OPT clinical trial program consists of five studies
(including one open-label, long-term extension study) evaluating oral
tofacitinib 5 mg and 10 mg BID in adults with moderate-to-severe chronic
plaque psoriasis. It is a global, multi-study, comprehensive clinical
development program that includes over 3,600 patients in 36 countries,
and is one of the largest global clinical trial programs in
moderate-to-severe chronic plaque psoriasis to date. The OPT Program is
designed to specifically evaluate tofacitinib in moderate-to-severe
chronic plaque psoriasis, and to support an independent assessment of
the benefit: risk profile of tofacitinib in this particular patient
population. In addition to OPT Compare, the OPT Program includes the
following Phase 3 studies of tofacitinib in psoriasis:
OPT Retreatment (A3921111): A phase 3 randomized, mixed-blid,
three-period, parallel group, placebo-controlled study evaluating the
efficacy and safety of the withdrawal and retreatment with tofacitinib
5 mg and 10 mg BID compared to placebo in adult patients with
moderate-to-severe chronic plaque psoriasis.
OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079): Two
Phase 3, 52-week, multi-site, randomized, double-blind,
placebo-controlled, parallel-group studies evaluating the safety and
efficacy of tofacitinib 5 mg and 10 mg BID. The primary objectives of
the studies are to compare the efficacy of tofacitinib to placebo for
the reduction in severity of plaque psoriasis as measured by the
proportion of patients achieving a PGA response of "clear" or "almost
clear," at week 16, and the proportion of patients achieving PASI75
relative to baseline at week 16, as well as to evaluate the safety and
tolerability of tofacitinib over 52 weeks.
OPT Extend (A3921061): An open-label long-term extension study
evaluating the safety and tolerability of tofacitinib. Patients who
participated in the Phase 2 trial or any of the other Phase 3 studies
had the option, if eligible, to enroll in this study.
About Plaque Psoriasis
Psoriasis is a chronic, immune-mediated skin disease, affecting the skin
and other organs, such as nails and joints. It affects approximately
two-to-three percent of people worldwide and 7.4 million in the United
States.1,2,3,4,5,6,7 Due to inconsistent response to
treatment, adverse effects, and the limited persistence of therapeutic
effects of some systemic therapies, a need for additional therapies for
patients with moderate-to-severe chronic plaque psoriasis still remains.8,9,10
According to a recent survey, approximately 50 percent of patients with
psoriasis are dissatisfied with their treatment, and under-treatment
represents a significant problem. Even though guidelines typically state
that moderate-to-severe patients are candidates for systemic therapy,
many treated adult plaque psoriasis patients appear to be undertreated,
with approximately 30 percent of treated moderate patients and 22
percent of treated severe patients receiving only topical therapy in the
About XELJANZ® (tofacitinib citrate)
Tofacitinib is approved in several markets around the world for the
treatment of rheumatoid arthritis (RA) in patients who had an inadequate
response to existing therapies. The brand name for tofacitinib is XELJANZ®
XELJANZ (tofacitinib citrate) 5 mg tablets is a prescription medicine
called a Janus kinase (JAK) inhibitor. XELJANZ is used to treat adults
with moderately to severely active rheumatoid arthritis in which
methotrexate did not work well.
It is not known if XELJANZ is safe and effective in people with
Hepatitis B or C.
XELJANZ is not for people with severe liver problems.
It is not known if XELJANZ is safe and effective in children.
Important Safety Information
XELJANZ can lower the ability of the immune system to fight
infections. Some people have serious infections while taking XELJANZ,
including tuberculosis (TB), and infections caused by bacteria, fungi,
or viruses that can spread throughout the body. Some people have died
from these infections. Healthcare providers should test patients for
TB before starting XELJANZ, and monitor them closely for signs and
symptoms of TB and other infections during treatment. People should
not start taking XELJANZ if they have any kind of infection unless
their healthcare provider tells them it is okay.
XELJANZ may increase the risk of certain cancers by changing the
way the immune system works. Malignancies were observed in clinical
studies of XELJANZ.
The risks and benefits of treatment should be considered prior to
initiating XELJANZ in patients with chronic or recurrent infection;
who have been exposed to tuberculosis; with a history of a serious or
an opportunistic infection; who have resided or traveled in areas of
endemic tuberculosis or endemic mycoses; or with underlying conditions
that may predispose them to infection.
Viral reactivation, including cases of herpes virus reactivation
(e.g., herpes zoster), was observed in clinical studies with XELJANZ.
Use of live vaccines should be avoided concurrently with XELJANZ.
Update immunizations in agreement with current immunization guidelines
prior to initiating XELJANZ therapy.
Some people who have taken XELJANZ with certain other medicines to
prevent kidney transplant rejection have had a problem with certain
white blood cells growing out of control (Epstein Barr
virus-associated post-transplant lymphoproliferative disorder).
Some people taking XELJANZ get tears in their stomach or intestines.
This happens most often in people who also take nonsteroidal
anti-inflammatory drugs (NSAIDs), corticosteroids, or methotrexate.
Patients should tell their healthcare provider right away if they have
fever and stomach-area pain that does not go away, or a change in
bowel habits. XELJANZ should be used with caution in patients who may
be at increased risk for gastrointestinal perforation (e.g., patients
with a history of diverticulitis).
XELJANZ can cause changes in certain lab test results including low
blood cell counts, increases in certain liver tests, and increases in
cholesterol levels. Healthcare providers should do blood tests before
starting patients on XELJANZ and while they are taking XELJANZ, to
check for these side effects. Normal cholesterol levels are important
to good heart health. Healthcare providers may stop XELJANZ treatment
because of changes in blood cell counts or liver test results.
Use of XELJANZ in patients with severe hepatic impairment is not
Patients should tell their healthcare providers if they plan to become
pregnant or are pregnant.
It is not known if XELJANZ will harm an unborn baby. To monitor the
outcomes of pregnant women exposed to XELJANZ, a registry has been
established. Physicians are encouraged to register patients and
pregnant women are encouraged to register themselves by calling
Patients should tell their healthcare providers if they plan to
breastfeed or are breastfeeding. Patients and their healthcare
provider should decide if they will take XELJANZ or breastfeed. They
should not do both.
In carriers of the hepatitis B or C virus (viruses that affect the
liver), the virus may become active while using XELJANZ. Healthcare
providers may do blood tests before and during treatment with XELJANZ.
Common side effects include upper respiratory tract infections (common
cold, sinus infections), headache, diarrhea, and nasal congestion,
sore throat, and runny nose (nasopharyngitis).
Please click the direct link to the full prescribing information for
XELJANZ, including boxed warning and Medication Guide: http://labeling.pfizer.com/ShowLabeling.aspx?id=959.
Pfizer Inc.: Working together for a healthier world®
At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
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more than 150 years, Pfizer has worked to make a difference for all who
rely on us. To learn more, please visit us at www.pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of
March 22, 2014. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information about tofacitinib,
including its potential benefits, that involves substantial risks and
uncertainties. Such risks and uncertainties include, among other things,
the uncertainties inherent in research and development, including,
without limitation, the ability to meet anticipated clinical trial
completion dates as well as the possibility of unfavorable clinical
trial results; whether and when any applications may be filed
with regulatory authorities in various jurisdictions for tofacitinib for
the treatment of moderate-to-severe chronic plaque psoriasis and whether
and when regulatory authorities may approve any such
applications, as well as their decisions regarding labeling and other
matters that could affect its availability or commercial potential; and
A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended December
31, 2013 and in its subsequent reports on Form 10-Q and Form 8-K.
1 Levy L, Solomon S, Emer J. Dove Medical Press Ltd.
Psoriasis: Targets and Therapy 2012:2 29-43.
2 Rachakonda T, Schupp CW, Armstrong AW. Psoriasis prevalence
among adults in the United States. J Am Acad Dermatol 2014; 70
3 Augustin M, Alvaro-Gracia JM, Bagot M., et al. A framework
for improving the quality of care for people with psoriasis. J Eur Acad
Dermatol. 2012;26 (Suppl. 4):1-16.
4 Perera GK, Di Meglio P, Nestle FO. Psoriasis. Annu Rev
Pathol Mech Dis. 2012;7:385-422.
5 Nestle FO, Kaplan DH, Barker J. Psoriasis. N Engl J Med.
6 Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care
for the management of psoriasis and psoriatic arthritis: Section 1.
Overview of psoriasis and guidelines of care for the treatment of
psoriasis with biologics. J Am Acad Dermatol. 2008;58(5):826-50.
7 Johnson MA, Armstrong AW. Clinical and histologic
diagnostic guidelines for psoriasis: a critical review. Clinic Rev
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Treatment Dissatisfaction Among Patients With Psoriasis and Psoriatic
Arthritis in the United States. Findings From the National Psoriasis
Foundation Surveys, 2003-2011. JAMA Dermatology. 2013; 5264.
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