Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today that
updated data from the Company’s Phase 1b multi-dose clinical trial
in chronic spontaneous urticaria (CSU) and new data from the Phase
1b single-dose cholinergic cohort included in the chronic inducible
urticaria (CIndU) trial were presented at the European Academy of
Allergy and Clinical Immunology (EAACI) Annual Congress 2023.
Barzolvolimab is a humanized monoclonal antibody that specifically
binds the receptor tyrosine kinase KIT with high specificity and
potently inhibits its activity, which is required for the function
and survival of mast cells. Data continue to support that mast cell
depletion by barzolvolimab, as demonstrated by tryptase
suppression, parallels symptom improvement.
The CSU data were presented by Dr. Marcus Maurer, Professor of
Dermatology and Allergy at Charité – Universitätsmedizin in Berlin,
in a late breaking oral presentation (#000401) and the cholingeric
data were presented by Dr. Eva Grekowitz, Clinical Investigator,
Department of Dermatology, Venerology and Allergy at Charité –
Universitätsmedizin in Berlin in an oral presentation
(#000393).
"As we expand development into more patients and new disease
settings, the data repeatedly support that barzolvolimab’s mast
cell depleting mechanism holds great potential to offer patients a
much needed rapid, profound and durable treatment option for
chronic urticarias— including patients who are not seeing
meaningful benefits from the current standard of care,” said Marcus
Maurer, M.D. “In the CSU study, we also observed very significant
improvements in angioedema which can be a devastating manifestation
of urticaria for many patients. In cholinergic urticaria,
barzolvolimab again demonstrated remarkable response rates and
impressive improvements in quality of life in this tough to treat
form of inducible urticaria."
"We are extremely pleased with these further results which once
again demonstrated strong clinical activity, rapid onset and
sustained durability with a well-tolerated safety profile,
including in patients who had previously taken omalizumab,"
commented Anthony S. Marucci, President and Chief Executive Officer
of Celldex Therapeutics. "These strong results support our ongoing
Phase 2 studies in urticaria. We look forward completing accrual
ahead of schedule in the Phase 2 CSU study later this month and
reporting topline data by the end of this year.”
Summary of Barzolvolimab Phase 1b Chronic Spontaneous
Urticaria (CSU) Data Update
CSU is characterized by the occurrence of hives or wheals for 6
weeks or longer without identifiable specific triggers or causes.
Treatment options for patients with CSU are limited and there are
no approved therapies for patients who do not respond to
omalizumab. Celldex’s Phase 1b study is a randomized, double-blind,
placebo-controlled clinical trial designed to assess the safety of
multiple ascending doses of barzolvolimab in patients with moderate
to severe CSU who remain symptomatic despite treatment with
antihistamines. Approximately 40% of patients with CSU report
accompanying episodes of angioedema, which typically presents as
swelling in the lips, cheeks, around the eyes, arms, legs, or
genitals1; patients with CSU and angioedema typically experience
significant negative impacts on health-related quality of life,
daily activities and productivity in work compared to patients with
CSU who do not have angioedema2.
Clinical Activity DataCelldex previously
presented interim Phase 1b CSU data at the American Academy of
Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2023. The
0.5 mg/kg, 1.5 mg/kg and 3.0 mg/kg cohorts had completed study
participation through 24 weeks; 6 of 9 patients in the 4.5 mg/kg
cohort had completed through the week 20 visit (last barzolvolimab
dose administered at 8 weeks). The study is now complete. At EAACI
2023, Celldex presented data on the complete 24 week experience for
the 4.5 mg/kg cohort and data on angioedema impact across all study
cohorts. 45 patients with moderate to severe CSU refractory to
antihistamines were enrolled and treated [35 barzolvolimab (n=9 in
0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg)
and 10 placebo]. Data for the 0.5 mg/kg and placebo group are only
outlined below through week 12 because, as expected, most patients
from these groups had significant symptoms ahead of week 24 and
discontinued follow up. Two patients did not receive all doses of
study treatment [4.5 mg/kg (1), placebo (1)].
- These data show that multiple doses of barzolvolimab resulted
in rapid dose-dependent decreases in itch and hives with durable
and prolonged symptom control in patients with moderate to severe
CSU refractory to antihistamines, including patients with prior
omalizumab treatment.
- Mean reduction from baseline in urticaria activity (UAS7) at
week 24 was 80% in the 1.5 mg/kg dose group (n=7), 70% in the 3.0
mg/kg dose group (n=6) and 77% in the 4.5 mg/kg dose group
(n=7).
- Complete response (UAS7=0) at week 24 was 57% in the 1.5 mg/kg
dose group, 67% in the 3.0 mg/kg dose group and 43% in the 4.5
mg/kg dose group.
- Well-controlled disease (UCT≥ 12) at week 24 was 75% in the 1.5
mg/kg dose group, 67% in the 3.0 mg/kg dose group and 67% in the
4.5 mg/kg dose group.
- During post-treatment follow up, 71% (10 of 14) of patients who
had been treated with doses greater than or equal to 1.5 mg/kg and
had a complete response (UAS7=0) at week 12, remained urticaria
free at week 24.
- Profound and durable improvement in angioedema symptoms as
measured through the angioedema activity score over 7 days (AAS7)
was achieved across all dose levels evaluated with sustained
activity observed with the 1.5 mg/kg and greater dose levels.
- 31 patients on study (n=26 barzolvolimab; 5=placebo) reported
angioedema activity at baseline when enrolling in the study. 86% of
the barzolvolimab treated patients at 1.5 mg/kg or greater were
angioedema free at week 12 and 83% were angioedema free at week
24.
Summary of Clinical Activity
Assessments
All Patients |
0.5 mg/kgQ4Wat Week
12 |
1.5 mg/kgQ4Wat Week
12/24 |
3.0 mg/kgQ8Wat Week
12/24 |
4.5 mg/kgQ8Wat Week
12/24 |
Placeboat Week 12 |
Baseline UAS7 (mean, range) |
31 (20 -39) |
30 (20 - 41) |
29 (16 - 42) |
28 (22 - 38) |
36 (19 - 42) |
UAS7 Changes |
Mean Score Change in UAS7 From Baseline |
-11 |
|
-18 / -23 |
-21 / -23 |
-24 / -24 |
-14 |
|
Mean % Change in UAS7 From Baseline |
-40 |
% |
-67% / -80% |
-67% / -70% |
-82% / -77% |
-37 |
% |
Clinical Responses** |
UAS7=0 (Complete Response) |
11 |
% |
57% / 57% |
44% / 67% |
67% / 43% |
13 |
% |
UAS7 ≤ 6 (Well-controlled) |
22 |
% |
57% / 57% |
67% / 67% |
67% / 57% |
13 |
% |
UCT ≥ 12 (Well-controlled) |
11 |
% |
75% / 75% |
63% / 67% |
89% / 67% |
33 |
% |
*24 week data not shown for 0.5 mg/kg and placebo dose levels as
most patients had significant symptoms ahead of week 24 and
discontinued follow up.The UAS7 score is calculated as the sum over
7 days of the daily intensity of itch (ISS7 itch severity score)
and number of hives (HSS7 hives severity score). UAS7 values range
from 0 to 42, with higher values reflecting higher disease
activity. UCT has 4 items with 5 answer options (scored with 0-4
points); recall period of 4 weeks. Low points indicate high disease
activity and low disease control. The minimum and maximum UCT
scores are 0 and 16, with 16 points indicating complete disease
control and ≥12 indicating well controlled disease.
** Clinical responses shown are the proportion of patients with
the defined response at the specific timepoint. Patients with
missing data at the timepont are excluded.
Safety DataBarzolvolimab was well tolerated
with a favorable safety profile; effects of multiple dose
administration were consistent with observations in single dose
studies. Most AEs were mild or moderate in severity and resolved
while on study.
Summary of Barzolvolimab Phase 1b Cholinergic (CIndU)
Data Results
Chronic inducible urticarias are forms of urticaria that have an
attributable trigger associated with them, typically resulting in
wheals (hives) or angioedema. Cholinergic urticaria, a form of
CindU, is triggered by physical exercise or passive warming and
characterized by itchy hives/wheals that appear upon sweating.
There are currently no approved therapies for chronic inducible
urticarias other than antihistamines and patients attempt to manage
symptoms associated with their disease through avoidance of
triggers.
Clinical Activity DataIn this open-label, Phase
1 trial, a cohort of patients with antihistamine refractory
cholinergic urticaria (n=9) received a single intravenous 3.0 mg/kg
barzolvolimab dose with a 12-week follow-up. Assessments included
provocation testing using pulse-controlled ergometry (PCE; complete
response, CR=no whealing within 40 min of test initiation),
urticaria control test (UCT), quality of life assessments, and
measurement of circulating tryptase and stem cell factor and skin
mast cell numbers. Safety assessments included adverse events and
clinical laboratory monitoring. Data reported at EAACI 2023 include
treatment and safety data through 12 weeks.
- 56% (5/9) patients achieved a complete response (negative
test) with PCE provocation testing with just one dose of
barzolvolimab and most responses remained durable through to week
12. PCE testing included controlled exercise on a stationary
bicycle with monitoring for development of itch and wheals.
- 63% (5/8) patients reported well controlled disease (UCT ≥12)
at week 8 and 50% (4/8) at week 12, respectively.
- 100% (6/6) patients who reported on quality of life (QoL)
measurements at week 8 had clinically significant improvements in
QoL. These improvements in QoL were sustained through week 12 for
the majority (5/7, 71%) of patients.
- The kinetics of tryptase and mast cell reduction mirrored
clinical activity
Safety DataBarzolvolimab was generally well
tolerated in patients with CholU, with a similar safety profile to
that reported previously. The most common AEs were mainly mild;
hair color changes (78%), nasopharyngitis (67%), taste disorders
(44%), and infusion related reactions (33%). Hematology
parameters were consistent with previous observation and generally
remained within the normal ranges. Mild, transient, and
asymptomatic decreases in hemoglobin and WBC parameters were
noted.
1JAllergy Clin Immunol Pract. 2018 Jul-Aug; 6(4): 1097–1106;
2Allergy 2018 Aug;73(8):1724-1734. doi:
10.1111/all.13430.
About BarzolvolimabBarzolvolimab is a humanized
monoclonal antibody that binds the receptor tyrosine kinase KIT
with high specificity and potently inhibits its activity. KIT is
expressed in a variety of cells, including mast cells, which
mediate inflammatory responses such as hypersensitivity and
allergic reactions. KIT signaling controls the differentiation,
tissue recruitment, survival and activity of mast cells. In certain
inflammatory diseases, such as chronic urticaria, mast cell
activation plays a central role in the onset and progression of the
disease.
About the Phase 1b CSU Study DesignThe Phase 1b
study is a randomized, double-blind, placebo-controlled clinical
trial designed to assess the safety of multiple ascending doses of
barzolvolimab in patients with moderate to severe CSU who remain
symptomatic despite treatment with antihistamines. Secondary and
exploratory objectives include pharmacokinetic and pharmacodynamic
assessments, including measurement of tryptase and stem cell factor
levels and clinical activity outcomes (impact on urticaria
symptoms, disease control, clinical response) as well as quality of
life assessments. The study enrolled 45 patients with CSU across
four cohorts. Barzolvolimab was administered intravenously at 0.5
mg/kg every 4 weeks (3 doses), 1.5 mg/kg every 4 weeks (3 doses), 3
mg/kg every 8 weeks (2 doses), 4.5 mg/kg every 8 weeks (2 doses),
as add-on treatment to H1-antihistamines, either alone or in
combination with H2-antihistamines and/or leukotriene receptor
agonists. Following completion of the 12 week treatment period,
patients were followed for an additional 12 weeks or until
resumption of symptoms, whichever was sooner. For additional
information on this trial (NCT04538794), please visit
www.clinicaltrials.gov.
About the Phase 1b CindU Study DesignThe Phase
1b study is an open label clinical trial designed to evaluate the
safety of a single dose of barzolvolimab in patients with cold
urticaria, symptomatic dermographism and cholinergic urticaria who
are refractory to antihistamines. Patients' symptoms are induced
via provocation testing that resembles real life triggering
situations. Secondary and exploratory objectives include
pharmacokinetic and pharmacodynamic assessments, including changes
from baseline provocation thresholds, measurement of tryptase and
stem cell factor levels, clinical activity outcomes (impact on
urticaria symptoms, disease control, clinical response), quality of
life assessments and measurement of tissue mast cells through skin
biopsies. The study enrolled 40 patients with inducible urticaria
across four cohorts (cold urticaria, symptomatic dermagraphism and
cholinergic urticaria at 3.0 mg/kg each and cold urticaria at 1.5
mg/kg). Barzolvolimab was administered intravenously as add on
treatment to H1-antihistamines and patients were followed for 12
weeks after dosing, with an optional longer term follow up period.
For additional information on this trial (NCT04548869), please
visit www.clinicaltrials.gov.
About Celldex Therapeutics, Inc.Celldex is a
clinical stage biotechnology company dedicated to developing
monoclonal and bispecific antibodies that address devastating
diseases for which available treatments are inadequate. Our
pipeline includes antibody-based therapeutics which have the
ability to engage the human immune system and/or directly affect
critical pathways to improve the lives of patients with
inflammatory diseases and many forms of cancer. Visit
www.celldex.com.
Forward Looking StatementThis release contains
"forward-looking statements" made pursuant to the safe harbor
provisions of the Private Securities Litigation Reform Act of 1995.
These statements are typically preceded by words such as
"believes," "expects," "anticipates," "intends," "will," "may,"
"should," or similar expressions. These forward-looking statements
reflect management's current knowledge, assumptions, judgment and
expectations regarding future performance or events. Although
management believes that the expectations reflected in such
statements are reasonable, they give no assurance that such
expectations will prove to be correct or that those goals will be
achieved, and you should be aware that actual results could differ
materially from those contained in the forward-looking statements.
Forward-looking statements are subject to a number of risks and
uncertainties, including, but not limited to, our ability to
successfully complete research and further development and
commercialization of Company drug candidates, including
barzolvolimab (also referred to as CDX-0159), in current or future
indications; the uncertainties inherent in clinical testing and
accruing patients for clinical trials; our limited experience in
bringing programs through Phase 3 clinical trials; our ability to
manage and successfully complete multiple clinical trials and the
research and development efforts for our multiple products at
varying stages of development; the effects of the outbreak of
COVID-19 on our business and results of operations; the
availability, cost, delivery and quality of clinical materials
produced by our own manufacturing facility or supplied by contract
manufacturers, who may be our sole source of supply; the timing,
cost and uncertainty of obtaining regulatory approvals; the failure
of the market for the Company's programs to continue to develop;
our ability to protect the Company's intellectual property; the
loss of any executive officers or key personnel or consultants;
competition; changes in the regulatory landscape or the imposition
of regulations that affect the Company's products; our ability to
continue to obtain capital to meet our long-term liquidity needs on
acceptable terms, or at all, including the additional capital which
will be necessary to complete the clinical trials that we have
initiated or plan to initiate; and other factors listed under "Risk
Factors" in our annual report on Form 10-K and quarterly reports on
Form 10-Q.
All forward-looking statements are expressly qualified in their
entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only
as of the date of this release. We have no obligation, and
expressly disclaim any obligation, to update, revise or correct any
of the forward-looking statements, whether as a result of new
information, future events or otherwise.
Company ContactSarah CavanaughSenior Vice
President, Corporate Affairs & Administration(508)
864-8337scavanaugh@celldex.com
Patrick TillMeru Advisors(484)
788-8560ptill@meruadvisors.com
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