Study achieves all co-primary and secondary endpoints
NEW YORK–(BUSINESS WIRE)–Pfizer Inc. (NYSE: PFE) announced today positive top-line results from a
Phase 3 pivotal study (B7451012) evaluating the efficacy and safety of
its investigational oral Janus kinase 1 (JAK1) inhibitor, abrocitinib
(PF-04965842), in patients aged 12 and older with moderate to severe
atopic dermatitis (AD).
B7451012 was a randomized, double-blind, placebo-controlled,
parallel-group study designed to evaluate the efficacy and safety of two
doses (100mg and 200mg once daily) of abrocitinib monotherapy over 12
weeks. Top-line results showed that by week 12 the percentage of
patients achieving each co-primary efficacy endpoint and each key
secondary endpoint with either dose of abrocitinib was statistically
significantly higher than placebo. In addition, the results demonstrate
response to treatment for a statistically significant number of patients
during the first two to four weeks following first dose.
“Moderate to severe atopic dermatitis is a chronic, inflammatory skin
disease that can take both a physical and emotional toll on the millions
of patients living with the condition worldwide,” said Michael Corbo,
PhD, Chief Development Officer, Inflammation & Immunology, Pfizer Global
Product Development. “These top-line findings are encouraging and
provide evidence that abrocitinib, if approved, could be an effective
new oral once-daily treatment option for patients.”
The co-primary study endpoints were the proportion of patients who
achieved an Investigator Global Assessment (IGA) score of clear (0) or
almost clear (1) skin and ≥2 point improvement; and the proportion of
patients who achieved at least a 75% or greater change from baseline in
their Eczema Area and Severity Index (EASI) score. The key secondary
endpoints were the proportion of patients achieving a 4 point or larger
reduction in itch severity measured with the pruritus numerical rating
scale (NRS) and the magnitude of decrease in the Pruritus and Symptoms
Assessment for Atopic Dermatitis (PSAAD).
Safety results show that both doses of abrocitinib were well-tolerated,
and there were no unexpected safety events. The discontinuation rates
due to an adverse event were low in each treatment arm (5.8% and 5.8% in
100mg and 200mg) compared to placebo (9.1%).
Additional Details About the Study
A total of 387 subjects were randomized to abrocitinib 200mg,
abrocitinib 100mg, and placebo in the trial. Randomization was
stratified by baseline disease severity (moderate [IGA=3] and severe
[IGA=4] AD) and age (age <18 and ≥18 years). Eligible subjects
completing the 12-week treatment period of the study had the option to
enter a long-term extension (LTE), study B7451015. Subjects
discontinuing early from treatment, or who were otherwise ineligible for
the LTE study, entered a 4-week follow up period in this study.
Detailed analyses of B7451012, including additional efficacy and safety
data, will be submitted for presentation at a future scientific meeting
and published in a prominent medical journal. B7451012 is the first
trial in the JAK1 Atopic Dermatitis Efficacy and Safety (JADE) global
development program. Additional data from another study in the JADE
program will be available later this year.
For additional information about B7451012, please visit https://www.clinicaltrials.gov.
About Abrocitinib (PF-04965842)
Abrocitinib (PF-04965842) is an oral small molecule that selectively
inhibits Janus kinase (JAK) 1. Inhibition of JAK1 is thought to modulate
multiple cytokines involved in pathophysiology of AD including
interleukin (IL)-4, IL-13, IL-31, and interferon gamma.
Abrocitinib received Breakthrough Therapy designation from the U.S. Food
and Drug Administration (FDA) for the treatment of patients with
moderate to severe AD in February 2018. Breakthrough Therapy designation
was initiated as part of the Food and Drug Administration Safety and
Innovation Act (FDASIA) signed in 2012. As defined by the FDA, a
breakthrough therapy is a drug intended to be used alone or in
combination with one or more other drugs to treat a serious or
life-threatening disease or condition, and preliminary clinical evidence
indicates that the drug may demonstrate substantial improvement over
existing therapies on one or more clinically significant endpoints, such
as substantial treatment effects observed early in clinical development.
If a drug is designated as a Breakthrough Therapy, the FDA will expedite
the development and review of such drug.1
About Atopic Dermatitis
AD is a chronic skin disease characterized by inflammation of the skin
and skin barrier defects.2,3 Lesions of AD are characterized
by erythema (redness), itching, induration (hardening)/papulation
(formulation of papules), and oozing/crusting.2,3
AD is one of the most common, chronic, relapsing childhood dermatoses,
affecting 1% to 3% of adults and 15% to 20% of children worldwide.4
Approximately 50% of pediatric AD patients globally have recurrent
symptoms into adolescence and adulthood.5,6
About Pfizer’s Kinase Inhibitor Leadership
The JAK pathways are believed to play an important role in inflammatory
processes as they are involved in signaling for over 50 cytokines and
growth factors, many of which drive immune-mediated conditions.7
JAK inhibition may offer patients with these conditions a potential new
advanced treatment option.8
Pfizer has established a leading kinase research capability with
multiple unique kinase inhibitor therapies in development. As a pioneer
in JAK science, the company is continuing to advance several
investigational programs for molecules with novel selectivity profiles,
which, if approved, could potentially deliver transformative therapies
for patients. In addition to abrocitinib, Pfizer has several kinase
inhibitors in clinical trials across multiple indications, including:
-
PF-06700841: A tyrosine kinase 2(TYK2)/JAK1 inhibitor under
investigation for the treatment of psoriasis, Crohn’s disease,
ulcerative colitis, vitiligo, and alopecia areata -
PF-06650833: An IL-1 receptor associated kinase 4 (IRAK4) inhibitor
under investigation for the treatment of rheumatoid arthritis -
PF-06826647: A TYK2 inhibitor under investigation for the treatment of
inflammatory bowel disease (IBD) -
PF-06651600: An oral, JAK3 inhibitor under investigation for the
treatment of alopecia areata, vitiligo, rheumatoid arthritis, Crohn’s
disease, and ulcerative colitis
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 of our time. Consistent with our responsibility as one of the
world’s premier innovative biopharmaceutical companies, we collaborate
with health care providers, governments, and local communities to
support and expand access to reliable, affordable health care around the
world. For more than 150 years, we have worked to make a difference for
all who rely on us. We routinely post information that may be important
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addition, to learn more, please visit us on www.pfizer.com
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DISCLOSURE NOTICE: The information contained in this release
is as of May 15, 2019. 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 a product
candidate, abrocitinib (PF-04965842), and Pfizer’s ongoing
investigational programs in kinase inhibitor therapies, including their
potential benefits, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical trials,
regulatory submission dates, regulatory approval dates and/or launch
dates, as well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when drug applications may be filed in any jurisdictions for any
potential indication for abrocitinib or any other investigational kinase
inhibitor therapies; whether and when any such applications may be
approved by regulatory authorities, which will depend on myriad factors,
including making a determination as to whether the product’s benefits
outweigh its known risks and determination of the product’s efficacy
and, if approved, whether abrocitinib or any such other investigational
kinase inhibitor therapies will be commercially successful; decisions by
regulatory authorities impacting labeling, manufacturing processes,
safety and/or other matters that could affect the availability or
commercial potential of abrocitinib or any other investigational kinase
inhibitor therapies; 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, 2018 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
# # # # #
1 U.S. Food and Drug Administration. Fact Sheet: Breakthrough
Therapies at https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantA…
accessed on January 25, 2018.
2 Hanifin JM, Reed ML. A population-based survey of eczema in
the United States. Dermatitis. 2007;18(2):82-91.
3 Bieber T. Atopic dermatitis. Dermatology. 2012;1(3):203-217.
4 Nutten S. Atopic dermatitis: global epidemiology and risk
factors. Ann Nutr Metab. 2015;66(suppl 1):8-16.
5 Williams HC Atopic Dermatitis 2005 N Eng J med 2005;
352:2314-2324 (v1.0).
6 Leung_2013 (v1.0).
7 Banerjee, S., Biehl, A., Gadina, M. et al. JAK–STAT
Signaling as a Target for Inflammatory and Autoimmune Diseases: Current
and Future Prospects. Drugs. 2017;77: 521. https://doi.org/10.1007/s40265-017-0701-9.
8 Telliez JB, Dowty ME, Wang L, Jussif J, Lin T, Li L, et al.
Discovery of a JAK3-selective inhibitor: functional differentiation of
JAK3-selective inhibition over pan-JAK or JAK1-selective inhibition. ACS
Chem Biol. 2016;11(12):3442–51. doi:10.1021/acschembio.6b00677.
Contacts
Media:
Steve Danehy, 212-733-1538
Steven.Danehy@pfizer.com
Investors:
Bryan Dunn, 212-733-8917
Bryan.Dunn@pfizer.com