NORTH CHICAGO, Ill.,
June 10, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced new data from a Phase 2a
study of ABBV-3373, an investigational anti-tumor necrosis factor
(TNF) Glucocorticoid Receptor Modulator (GRM) steroid antibody drug
conjugate (ADC), in adult patients with moderate to severe
rheumatoid arthritis.1 The primary endpoint was the
change in Disease Activity Score 28 C-Reactive Protein (DAS28-CRP)
from baseline to week 12 and two statistical comparisons were
pre-specified.1 The first compared ABBV-3373 and
mean outcome from historical adalimumab data.1 The
second compared ABBV-3373 and combined in-trial and historical
adalimumab data.1 Results of the first comparison
show a greater difference in the primary endpoint change in
DAS28-CRP from baseline to week 12 for ABBV-3373 (-2.65) as
compared to a pre-specified historical adalimumab mean (-2.13)
(p=0.022).1 Results of the second comparison, based
on a Bayesian analysis, predicted with a 90 percent probability
that ABBV-3373 was associated with a greater improvement on
DAS28-CRP from baseline to week 12 than adalimumab based on
in-trial data combined with historical
data.1 Additionally, evaluations of serum cortisol
levels over 12 weeks indicate that ABBV-3373 showed no systemic
glucocorticoid effects.1
"This proof of concept study demonstrates clinical activity of
the TNF-ADC platform and its potential to advance the standard of
care for patients with rheumatoid arthritis," said Michael Severino, M.D., vice chairman and
president, AbbVie. "Based on these results we will advance the
development of the TNF-ADC platform in rheumatoid arthritis and
begin clinical studies in other immune-mediated diseases."
These are the first results to be reported for the novel ADC in
rheumatoid arthritis. ABBV-3373 is an investigational medicine that
is not approved by regulatory authorities and is being studied for
the treatment of rheumatoid arthritis and other immune-mediated
diseases.1,2 Full results from this study will be
presented at an upcoming medical meeting and/or published in a
peer-reviewed publication.
In the 31 rheumatoid arthritis patients on ABBV-3373 and 17
rheumatoid arthritis patients on adalimumab, in the trial, the
safety profile of ABBV-3373 was generally similar to
adalimumab.1 The overall adverse events (AE) rate
of ABBV-3373 was lower than adalimumab (35 percent [n=11] vs. 71
percent [n=12], respectively).1 The AEs occurring
in ≥5 percent of patients were urinary tract infections, with two
events in each treatment group, and headache, with two events in
the ABBV-3373 group and one event in the adalimumab
group.1 Six percent (n=1) of subjects treated with
adalimumab and three percent (n=1) of subjects treated with
ABBV-3373 discontinued treatment due to an
AE.1 Through week 12, serious adverse events (SAEs)
occurred in four patients in the ABBV-3373 group (13 percent,
[n=4]), compared to none in the adalimumab group (0 percent,
[n=0]).1 In the ABBV-3373 group, two SAEs were
deemed unrelated to study drug (pneumonia and upper respiratory
tract disease).1 One SAE was non-cardiac chest pain
and one SAE was reported as anaphylactic shock; this subject fully
recovered and no further events of hypersensitivity were reported
after drug administration time was extended for subsequently dosed
subjects.1
About ABBV-33731,2
Being developed by AbbVie, ABBV-3373 is an investigational ADC
comprised of a novel glucocorticoid receptor modulator (GRM) linked
to adalimumab, and aims at modulating TNF-mediated inflammatory
pathways by delivering a glucocorticoid payload directly into
activated immune cells expressing membrane bound TNF. This ADC was
designed to potentially allow precise targeting of activated immune
cells while significantly dampening inflammation and minimizing the
systemic side-effects associated with glucocorticoids. ABBV-3373 is
an investigational medicine that is not approved by regulatory
authorities and is being studied for the treatment of rheumatoid
arthritis and other immune-mediated diseases.
About the M16-560 Study1,2
The M16-560 study is a Phase 2a, multicenter, randomized,
double-blind, double-dummy, active-controlled study designed to
evaluate the safety, tolerability, pharmacokinetics and efficacy of
ABBV-3373 in adult patients with moderate to severe rheumatoid
arthritis with an inadequate response to MTX. Patients were
randomized in a 2:1 ratio to ABBV-3373 (n=31) at 100 mg, every
other week (EOW) or adalimumab (n=17) at 80 mg, EOW for 12
weeks.
Bayesian statistical methods incorporating historical data were
used to achieve adequate statistical power in this proof of concept
study, which was accomplished through pre-specified supplementation
of adalimumab in-trial data with historical adalimumab data for
comparison with ABBV-3373 for the primary endpoint analyses. The
historical data were obtained from three historical adalimumab
trials of similar settings. The primary endpoint was the change in
DAS28-CRP from baseline to week 12 and two statistical comparisons
were pre-specified. The first compared ABBV-3373 and mean outcome
from historical adalimumab data with the success criteria of
two-sided p-value ≤0.1. The second compared ABBV-3373 and combined
in-trial and historical adalimumab data (success criterion:
probability of >95 percent).
Important Safety Information about HUMIRA™
(adalimumab)3
HUMIRA U.S. Use and Important Safety Information
HUMIRA is a prescription medicine used to reduce the signs and
symptoms of moderate to severe rheumatoid arthritis in adults.
HUMIRA can be used alone, with methotrexate, or with certain other
medicines. HUMIRA may prevent further damage to bones and joints
and may help the ability to perform daily activities.
HUMIRA is a TNF blocker medicine that affects the immune system
and can lower the body's ability to fight infections. Serious
infections have happened in people taking HUMIRA. These serious
infections include tuberculosis (TB) and infections caused by
viruses, fungi, or bacteria that have spread throughout the body.
Some people have died from these infections. People should be
tested for TB before HUMIRA use and monitored for signs and
symptoms of TB during therapy, even if their TB test was negative.
People at risk of TB may be treated with medicine for TB. Treatment
with HUMIRA should not be started in a person with an active
infection, unless approved by a doctor. HUMIRA should be stopped if
a person develops a serious infection. People should tell their
doctor if they live in or have been to a region where certain
fungal infections are common, as these infections may happen or
become more severe if people use HUMIRA. People should tell their
doctor if they have had TB or hepatitis B, are prone to infections,
or have symptoms such as fever, fatigue, cough, or sores.
For people taking TNF blockers, including HUMIRA, the chance of
getting lymphoma or other cancers may increase. Some people have
developed a rare type of cancer called hepatosplenic T-cell
lymphoma. This type of cancer often results in death. If using TNF
blockers, including HUMIRA, the chance of getting two types of skin
cancer (basal cell and squamous cell) may increase. These types are
generally not life-threatening if treated.
Other possible serious side effects with HUMIRA include
hepatitis B infection in carriers of the virus; allergic reactions;
nervous system problems; blood problems; certain immune reactions,
including a lupus-like syndrome; liver problems; and new or
worsening heart failure or psoriasis. The use of HUMIRA with
anakinra or abatacept is not recommended. People using HUMIRA
should not receive live vaccines. Children should be brought up to
date on all vaccines before starting HUMIRA.
Common side effects of HUMIRA include injection site reactions
(redness, rash, swelling, itching, or bruising), upper respiratory
infections (including sinus infections), headaches, rash, and
nausea.
HUMIRA is given by injection under the skin.
The benefits and risks of HUMIRA should be carefully considered
before starting therapy.
Please click here for the Full Prescribing
Information and Medication
Guide.
This is the most important information to know about HUMIRA.
For more information, talk to your HCP.
You are encouraged to report negative side effects of
prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call
1-800-FDA-1088
About AbbVie in Rheumatology
For more than 20 years, AbbVie has been dedicated to improving
care for people living with rheumatic diseases. Our longstanding
commitment to discovering and delivering transformative therapies
is underscored by our pursuit of cutting-edge science that improves
our understanding of promising new pathways and targets in order to
help more people living with rheumatic diseases reach their
treatment goals. For more information on AbbVie in rheumatology,
visit
https://www.abbvie.com/our-science/therapeutic-focus-areas/immunology/immunology-focus-areas/rheumatology.html.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
that solve serious health issues today and address the medical
challenges of tomorrow. We strive to have a remarkable impact on
people's lives across several key therapeutic areas: immunology,
oncology, neuroscience, eye care, virology, women's health and
gastroenterology, in addition to products and services across its
Allergan Aesthetics portfolio. For more information about AbbVie,
please visit us at www.abbvie.com. Follow @abbvie on Twitter,
Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statements
Some statements in this news release are, or may be considered,
forward-looking statements for purposes of the Private Securities
Litigation Reform Act of 1995. The words "believe," "expect,"
"anticipate," "project" and similar expressions, among others,
generally identify forward-looking statements. AbbVie cautions that
these forward-looking statements are subject to risks and
uncertainties that may cause actual results to differ materially
from those indicated in the forward-looking statements. Such risks
and uncertainties include, but are not limited to, competition from
other products, challenges to intellectual property, difficulties
inherent in the research and development process, adverse
litigation or government action, and changes to laws and
regulations applicable to our industry. Additional information
about the economic, competitive, governmental, technological and
other factors that may affect AbbVie's operations is set forth in
Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. AbbVie undertakes no obligation to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
References:
- AbbVie. Data on File: ABVRRTI70670.
- A Study to Evaluate the Safety, Tolerability, Pharmacokinetics,
and Efficacy of ABBV-3373 and ABBV-154 in Participants With
Moderate to Severe Rheumatoid Arthritis. 2020. ClinicalTrials.gov.
Available at: https://clinicaltrials.gov/ct2/show/NCT03823391.
Accessed on June 9, 2020.
- HUMIRA (adalimumab) [Package Insert]. North Chicago, Ill.: AbbVie Inc.
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SOURCE AbbVie