|[May 23, 2014]
Pfizer Announces Detailed Results For Phase 3 OPT Retreatment Study Of Tofacitinib In Adults With Moderate-To-Severe Chronic Plaque Psoriasis
NEW YORK --(Business Wire)--
Pfizer Inc. (NYSE:PFE) announced today detailed results from the Oral
treatment Psoriasis Trial
(OPT) Retreatment study (A3921111), a Phase 3 study investigating
tofacitinib for the treatment of adult patients with moderate-to-severe
chronic plaque psoriasis. This three-period study showed that
tofacitinib, as a 5 mg or 10 mg pill taken twice daily, met its two
primary efficacy endpoints. The safety profile of tofacitinib in OPT
Retreatment was consistent with previous studies and there were no new
safety findings in this trial.
The first primary endpoint of OPT Retreatment evaluated the maintenance
of clinical response in patients who remained on tofacitinib after an
initial treatment phase compared to patients who were switched to
placebo (withdrawal phase). The second primary endpoint examined
patients who lost half of their original clinical response during the
withdrawal phase, and measured the proportion of these patients who
regained their original clinical response after restarting treatment
with tofacitinib. Throughout the study, the efficacy response was
measured by the proportion of subjects achieving a Physician's Global
Assessment (PGA) response of "clear" or "almost clear" skin and the
proportion of subjects achieving at least a 75% reduction in the
Psoriasis Area and Severity Index (PASI75), two commonly used measures
of efficacy in psoriasis.
"Psoriasis is a chronic disease that affects approximately two-to-three
percent of people worldwide, and there are times when patients with
psoriasis may need to stop and restart therapy for medical or
non-medical reasons, such as elective surgery or receipt of live
immunizations," said lead investigator Robert Bissonnette, M.D.,
Innovaderm Research, Montreal, QC, Canada. "The OPT Retreatment data
showed that patients who stayed on therapy with tofacitinib maintained
their rates of response and for those who stopped therapy, a proportion
of patients were able to regain their original clinical response when
retreated with tofacitinib."
Tofacitinib, an oral Janus kinase (JAK) inhibitor, is part of a new
class of medicines in development for the treatment of
moderate-to-severe plaque psoriasis. Top-line results from OPT
Retreatment were previously announced in October 2013, and the detailed
results of this study were shown today in an oral presentation during
the 11th European Academy of Dermatology and Venereology (EADV) Spring
Symposium in Belgrade, Serbia.
OPT Retreatment was a Phase 3 randomized, double-blind, three-period,
parallel group, placebo-controlled 56-week study. This study evaluated
the efficacy and safety of the withdrawal and retreatment with
tofacitinib 5 mg and 10 mg twice daily compared to placebo in 674 adult
patients with moderate-to-severe chronic plaque psoriasis. During the
first period (24 weeks), which was a secondary endpoint of this study,
patients were treated with either tofacitinib at a dose of 5 mg or 10 mg
twice daily in a blinded manner. During this initial 24 weeks of
44% and 68% of patients who received tofacitinib 5 mg and 10 mg twice
daily achieved at least a 75% reduction in the Psoriasis Area and
Severity Index (PASI75), respectively, and
42% and 63% of patients who received tofacitinib 5 mg and 10 mg twice
daily achieved a PGA response of "clear" or "almost clear" skin,
The patients who achieved a PASI75 and PGA response were then randomized
to either continue tofacitinib or switch to placebo for 16 weeks or
until they lost half of their original PASI response to treatment,
whichever occurred first. During this withdrawal period:
A statistically significantly greater proportion of patients who
remained on both doses of tofacitinib maintained PASI75 and PGA
responses relative to patients who were switched to placebo, and
No patients experienced psoriasis rebound (rapidly spreading psoriasis
after treatment withdrawal).
In the retreatment period, all patients resumed their original
tofacitinib dose until week 56. After 16 weeks of restarting therapy
with tofacitinib, the efficacy response was evaluated in the proportion
of patients who lost half of their original PASI or PGA response during
the withdrawal phase and showed that:
36.8% and 61.0% of patients who received tofacitinib 5 mg and 10 mg
twice daily, respectively, achieved a PASI75; and
44.8% and 57.1% of patients who received tofacitinib 5 mg and 10 mg
twice daily, respectively, achieved a PGA of "clear" or "almost clear"
The most common adverse events for all study periods were
nasopharyngitis and upper respiratory tract infection. There was one
cardiac-related death that occurred during the OPT Retreatment study at
the 5 mg dose. However, in the opinion of the investigator, there was
not a reasonable possibility that this death was related to tofacitinib.
OPT Retreatment is one of five studies from the Phase 3 OPT Clinical
Trial Program, one of the largest global clinical trial programs in
moderate-to-severe chronic plaque psoriasis to date. The results from
this study will be included in the planned tofacitinib psoriasis
submission package to regulatory authorities in various markets. Pfizer
currently intends to submit a supplemental New Drug Application (sNDA)
to the U.S. Food and Drug Administration (FDA) for the approval of
tofacitinib for the treatment of adults with moderate-to-severe chronic
plaque psoriasis by early 2015.
About the OPT Clinical Trial Program
The Phase 3 OPT clinical trial program consists of five studies
(including one long-term extension study) evaluating oral tofacitinib 5
mg and 10 mg twice daily in adults with moderate-to-severe chronic
plaque psoriasis. It is a global, 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. In addition to the OPT Retreatment study, the
OPT Program includes the following Phase 3 studies of tofacitinib in
adults with moderate-to-severe plaque psoriasis:
OPT Pivotal #1 (A3921078) and OPT Pivotal #2 (A3921079): OP
Pivotal #1 and OPT Pivotal #2 are 52-week, randomized, double-blind,
placebo-controlled, parallel-group studies evaluating the safety and
efficacy of tofacitinib 5 mg and 10 mg twice daily in patients who are
candidates for systemic therapy or phototherapy. There were over 900
patients randomized into the each of the studies. As previously
announced in April 2014, the OPT Pivotal #1 and OPT Pivotal #2 studies
showed that tofacitinib, as a 5 mg or a 10 mg dose taken as a pill
twice daily, met the primary efficacy endpoints of statistically
significant superiority over placebo at Week 16 in the proportion of
subjects achieving a PGA response of "clear" or "almost clear" skin,
and the proportion of subjects achieving at least a 75% reduction in
Psoriasis Area and Severity Index (PASI75).
OPT Compare (A3921080): A 12-week, Phase 3 study
comparing the efficacy and safety of tofacitinib 5 mg and 10 mg twice
daily to high-dose ENBREL® (etanercept) 50 mg twice weekly as well as
to placebo. There were 1,106 patients enrolled in this study.
OPT Extend (A3921061): A 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 disease, affecting primarily the
skin but also other organs, such as nails and joints. It affects
approximately two-to-three percent of people worldwide and 7.4 million
people 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 therapies, a need for additional therapies
for patients with moderate-to-severe chronic plaque psoriasis remains.8,9,10
According to recent published surveys, 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 - e.g., medicines given by mouth or an injection - many
adult plaque psoriasis patients appear to be undertreated. Approximately
30 percent of treated moderate patients and 22 percent of treated severe
patients receive only topical therapies like ointments and creams in the
XELJANZ® (tofacitinib citrate) 5 mg Tablets RA U.S. Label
Tofacitinib is currently approved in more than 20 countries around the
world for the treatment of moderate-to-severe rheumatoid arthritis. In
the U.S., the brand name for tofacitinib is XELJANZ® (ZEL'
JANS'), and it is approved at the 5 mg dose for the treatment of adults
with moderately to severely active rheumatoid arthritis who have had an
inadequate response or intolerance to methotrexate.
XELJANZ 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 1-877-311-8972.
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
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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
May 23, 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 and the anticipated submission of
applications with regulatory authorities, 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 an sNDA will be submitted in the U.S. by
early 2015, and whether and when any applications may be submitted
with regulatory authorities in various other jurisdictions, for
tofacitinib for the treatment of moderate-to-severe chronic plaque
psoriasis; whether and when the FDA and regulatory authorities in other
jurisdictions may approve any such applications, as well as their
decisions regarding labeling and other matters that could affect its
availability or commercial potential; and competitive developments.
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.
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2 Rachakonda T, Schupp CW, Armstrong AW. Psoriasis prevalence
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